Embed Size (px)
Citation preview
Histopatologia da bioacutepsia prostaacutetica
Antonio Beltran
Centro Clinico Champalimaud
Lisboa
2018
Histologic Type
Greater than 99 of all PCAs seen in needle biopsy specimens are referred to as acinar microacinar or conventional type
Not necessary to specify such
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
bullBefore 2014 1966 Gleason system
1974 and 1977 Gleasonrsquos modifications
2005 ISUP modified Gleason system
2008-2010 Update of the Gleason grading system
2013 Epstein prognostic Gleason gradegrouping
bullFrom 2014 onward 2014 Chicago ISUP Grading Meeting
201520162017 Major publications
Prostate cancer grading Historical perspective
Courtesy of Prof Theo van der Kwast (2015)
Before 2014
Mazzucchelli Scarpelli Lopez-Beltran Cheng Di Primio and Montironi Eur J Inflam 2013
Grading according to the Gleason system
WHO 2016
Objectives of the 2014 ISUP Conference
bullScores 2-5 are currently no longerassigned and certain patterns thatGleason defined as a score of 6 arenow graded as 7
bullThus leading to contemporary Gleasonscore 6 cancers having a betterprognosis than historic score 6 cancers
Epstein et al Am J Surg Pathol 2016 40244-52
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
2018
Histologic Type
Greater than 99 of all PCAs seen in needle biopsy specimens are referred to as acinar microacinar or conventional type
Not necessary to specify such
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
bullBefore 2014 1966 Gleason system
1974 and 1977 Gleasonrsquos modifications
2005 ISUP modified Gleason system
2008-2010 Update of the Gleason grading system
2013 Epstein prognostic Gleason gradegrouping
bullFrom 2014 onward 2014 Chicago ISUP Grading Meeting
201520162017 Major publications
Prostate cancer grading Historical perspective
Courtesy of Prof Theo van der Kwast (2015)
Before 2014
Mazzucchelli Scarpelli Lopez-Beltran Cheng Di Primio and Montironi Eur J Inflam 2013
Grading according to the Gleason system
WHO 2016
Objectives of the 2014 ISUP Conference
bullScores 2-5 are currently no longerassigned and certain patterns thatGleason defined as a score of 6 arenow graded as 7
bullThus leading to contemporary Gleasonscore 6 cancers having a betterprognosis than historic score 6 cancers
Epstein et al Am J Surg Pathol 2016 40244-52
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Histologic Type
Greater than 99 of all PCAs seen in needle biopsy specimens are referred to as acinar microacinar or conventional type
Not necessary to specify such
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
bullBefore 2014 1966 Gleason system
1974 and 1977 Gleasonrsquos modifications
2005 ISUP modified Gleason system
2008-2010 Update of the Gleason grading system
2013 Epstein prognostic Gleason gradegrouping
bullFrom 2014 onward 2014 Chicago ISUP Grading Meeting
201520162017 Major publications
Prostate cancer grading Historical perspective
Courtesy of Prof Theo van der Kwast (2015)
Before 2014
Mazzucchelli Scarpelli Lopez-Beltran Cheng Di Primio and Montironi Eur J Inflam 2013
Grading according to the Gleason system
WHO 2016
Objectives of the 2014 ISUP Conference
bullScores 2-5 are currently no longerassigned and certain patterns thatGleason defined as a score of 6 arenow graded as 7
bullThus leading to contemporary Gleasonscore 6 cancers having a betterprognosis than historic score 6 cancers
Epstein et al Am J Surg Pathol 2016 40244-52
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
bullBefore 2014 1966 Gleason system
1974 and 1977 Gleasonrsquos modifications
2005 ISUP modified Gleason system
2008-2010 Update of the Gleason grading system
2013 Epstein prognostic Gleason gradegrouping
bullFrom 2014 onward 2014 Chicago ISUP Grading Meeting
201520162017 Major publications
Prostate cancer grading Historical perspective
Courtesy of Prof Theo van der Kwast (2015)
Before 2014
Mazzucchelli Scarpelli Lopez-Beltran Cheng Di Primio and Montironi Eur J Inflam 2013
Grading according to the Gleason system
WHO 2016
Objectives of the 2014 ISUP Conference
bullScores 2-5 are currently no longerassigned and certain patterns thatGleason defined as a score of 6 arenow graded as 7
bullThus leading to contemporary Gleasonscore 6 cancers having a betterprognosis than historic score 6 cancers
Epstein et al Am J Surg Pathol 2016 40244-52
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
bullBefore 2014 1966 Gleason system
1974 and 1977 Gleasonrsquos modifications
2005 ISUP modified Gleason system
2008-2010 Update of the Gleason grading system
2013 Epstein prognostic Gleason gradegrouping
bullFrom 2014 onward 2014 Chicago ISUP Grading Meeting
201520162017 Major publications
Prostate cancer grading Historical perspective
Courtesy of Prof Theo van der Kwast (2015)
Before 2014
Mazzucchelli Scarpelli Lopez-Beltran Cheng Di Primio and Montironi Eur J Inflam 2013
Grading according to the Gleason system
WHO 2016
Objectives of the 2014 ISUP Conference
bullScores 2-5 are currently no longerassigned and certain patterns thatGleason defined as a score of 6 arenow graded as 7
bullThus leading to contemporary Gleasonscore 6 cancers having a betterprognosis than historic score 6 cancers
Epstein et al Am J Surg Pathol 2016 40244-52
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Courtesy of Prof Theo van der Kwast (2015)
Before 2014
Mazzucchelli Scarpelli Lopez-Beltran Cheng Di Primio and Montironi Eur J Inflam 2013
Grading according to the Gleason system
WHO 2016
Objectives of the 2014 ISUP Conference
bullScores 2-5 are currently no longerassigned and certain patterns thatGleason defined as a score of 6 arenow graded as 7
bullThus leading to contemporary Gleasonscore 6 cancers having a betterprognosis than historic score 6 cancers
Epstein et al Am J Surg Pathol 2016 40244-52
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Mazzucchelli Scarpelli Lopez-Beltran Cheng Di Primio and Montironi Eur J Inflam 2013
Grading according to the Gleason system
WHO 2016
Objectives of the 2014 ISUP Conference
bullScores 2-5 are currently no longerassigned and certain patterns thatGleason defined as a score of 6 arenow graded as 7
bullThus leading to contemporary Gleasonscore 6 cancers having a betterprognosis than historic score 6 cancers
Epstein et al Am J Surg Pathol 2016 40244-52
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Objectives of the 2014 ISUP Conference
bullScores 2-5 are currently no longerassigned and certain patterns thatGleason defined as a score of 6 arenow graded as 7
bullThus leading to contemporary Gleasonscore 6 cancers having a betterprognosis than historic score 6 cancers
Epstein et al Am J Surg Pathol 2016 40244-52
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
ISUP 2005
Modified
Gleason
Prognostic Gleason grade
grouping(7869 men)
GS le 6 (3 + 3) I (1)
GS 7 (3 + 4) II (2)
GS 7 (4 + 3) III (3)
GS 8 (4 + 4)
GS 8 (3 + 5)IV (4)
GS 9 - 10 V (5)
BJU International 2013111 753ndash
760
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
2014 ISUP Conference main topics
2014 ISUP modified Gleason system
Prognostic grade grouping (5-tiered grading prognostic system)
Epstein et al Am J Surg Pathol 2016 40244-52
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
2014 ISUP modified Gleason system
1 Cribriform glands should be considered as aGleason pattern 4 regardless of their histology
2 Glands with glomeruloid features should beassigned a pattern 4
3 Further definition of Gleason pattern 4
4 IDC not associated with invasive PAC is notgraded
5 Grading of PAC with mucinous features should bebased on its underlying architectural patternrather than considering all of them as pattern 4
Epstein et al Am J Surg Pathol 2016 40244-52
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Cribriform pattern
3
Cribriform pattern
4
Am J Surg Pathol 2005
Sept291228-42
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Intraductal
Carcinoma
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
2016
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Gleason pattern 4 further definition
1 Gleason pattern 4 includes cribriformglomeruloid fused and poorly formed glands
2 For a diagnosis of Gleason pattern 4 it needs tobe seen at 10x lens magnification
3 Occasionalseemingly poorly formed or fusedglands between well-formed glands isinsufficient for a diagnosis of pattern 4
4 In cases with borderline morphology betweenGleason pattern 3 and pattern 4 the lower gradeshould be favored
Epstein et al Am J Surg Pathol 2016 40244-52
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Small-fused
GlomeruloidCribriform
Large-fused
Gleason grade 4 patterns
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Histopathology 2014 Feb64(3)405-11 doi 101111his12284 Epub 2013 Nov 6
The reasons behind variation in Gleason grading of prostatic biopsies areas of
agreement and misconception among 266 European pathologists
Berney DM1 Algaba F Camparo P Compeacuterat E Griffiths D Kristiansen G Lopez-Beltran A
Montironi R Varma M Egevad L
CONCLUSION
Misinterpretation of ISUP 2005 is widespread and may explain the variation in
Gleason scoring seen Clarity and uniformity in teaching ISUP 2005 recommendations
is necessary
Cribriform glands GS 3 gtgt51
Necrosis GS 5 gtgt62Tertiary GS5 gtgt58
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 4+4=8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score lt=6)-censurado
Grade Group 5 ( Gleason score 9-10)
Grade Group 4 (Gleason score 4+4=8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
GS7
Trudel et al 2014
Triptocare duct-like features
39 Mean 14
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
bullGroup 1 10
bullGroup 2 26
bullGroup 3 85
bullGroup 4 168
bullGroup 5 293
(All curves significantly different by plt000001)
Prognostic grade grouping (GG)Hazard Ratios Relative to Group 1
Epstein et al Am J Surg Pathol 2016 40244-52
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
bullGroup 1 Very low risk
bullGroup 2 Low risk
bullGroup 3 Intermediaterisk
bullGroup 4 High risk
bullGroup 5 Highest risk
Hazard Rations Relative to Group 1
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Study No (First
author)No of patients
Biopsy (pre-
prostatectomy)
Radical
prostatectomy
Biopsy (pre-
radiation
therapy)
Prognosis
1 (Epstein)
26346
(20845 +
5501)
yes yes yesbiochemical
recurrence
2 (Samaratunga) 2079 yes
biochemical
recurrence-
free survival
3 (Delahunt) 496
Yes (+
androgen
ablation)
biomedical
(PSA) control
and survival
4 (Loeb)5880 (4325
+ 1555)yes yes
4-yr
biochemical
recurrence-free
survival
5 (Ancona) 395 yes survival
6 (Berney) 988 YesProstare cancer
death
Montironi Lopez-Beltran et al Expert Rev Anticancer Res 2016
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Biochemical recurrence after RP
Time (months)
6050403020100
Su
rviv
al
10
08
06
04
02
00
Grade Group 4 (Gleason score 8)-censurado
Grade Group 3 (Gleason score 4+3=7)-censurado
Grade Group 2 (Gleason score 3+4=7)-censurado
Grade Group 1 (Gleason score =6)-censurado
Grade Group 5 (Gleason scores 9-10)
Grade Group 4 (Gleason score 8)
Grade Group 3 (Gleason score 4+3=7)
Grade Group 2 (Gleason score 3+4=7)
Grade Group 1 (Gleason score le6)
Epstein Grade Group (Tumor Index)
Chi-cuadrado gl SigLog Rank (Mantel-Cox) 58768 4 000
Breslow (Generalized Wilcoxon) 53755 4 000
Tarone-Ware 56428 4 000Lopez-Beltran et al 2018
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
2014 ISUP grading significantly out-performs 2005 MGS
grading
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Genomic correlates to the newly proposed prognostic grade group for prostate cancer
bull Whole exome and whole genomesequencing data from 426clinically localized PAC treatedby RP
bull Principal Component Analysiswas used to identify distinctgenomic profiles between the 5PGGs supporting PGG 1through PGG 3 as distinct classesbut revealing genomic similarityfor PGG 4 and PGG 5
Rubin et al Eur Urol 2016
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Amount of tumor in prostate needle cores (extent of involvement of needle core)
bull The extent of needle core involvement including bilateral involvement
bull Predicts biochemical recurrence post-prostatectomy progression and radiation therapy failure in univariate and often in multivariate analysis
bull It is a parameter included in some recent nomograms created to predict pathologic stage and seminal vesicle invasion after radical prostatectomy and radiation therapy failure
bull The report should provide at leastbull The number of involved cores (OR of
cores involved)bull The linear length of cancer in mm ORbull of each core involved
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Amount of tumor in prostate needle cores
(extent of involvement of needle core)
Positive cores
12gtgtgt27 T3
gt3gtgtgt43 T3
positive tissue
lt 40 18 T3
40-60 36 T3
61-80 41 T3
gt 80 54 T3AJSP 2000
GS 3+3
PRAD-3
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Local invasion
bull Routine biopsy sampling may occasionally contain extraprostatic fat or seminal vesicle tissue
bull Indicate pT3ab disease
bull High Gleason score
bull The presence of seminal vesicle invasion or extraprostatic fat involvement in the staging biopsy is highly correlative of similar findings at RP
bull Extraprostatic fat invasion at needle biopsy is highly predictive of biochemical recurrence (79 compared to 43 failure rate)
26
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Perineural invasion
bull Definition Perineural invasionbull The presence of prostate cancer
juxtaposed intimately along around orwithin a nerve
bull The significance of perineural invasionin diagnostic biopsies is controversial
bull Extensive (multifocal) perineuralinvasion and greater nerve diameteror full encircling
bull Involvement of nerves present withinadipose tissue (extraprostatic nerves)by cancer indicates extraprostaticextension and deserves notation in thepathology report when present
64
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Perineural invasionbull Although perineural invasion in needle biopsy
specimens is not an independent predictor of prognosis when the Gleason score serum PSA and extent of cancer are factored in most studies indicate that its presence correlates with extraprostatic extension (38-93)
bull Seem not being related to M+ status (Marks et al 2007)
bull Some of the data from the radiation oncology literature suggests that it is an independent risk factor for predicting adverse outcome after external beam radiation therapy (Yu et al 2007)
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Lymphovascular invasionbull Since lymphovascular invasion as
studied in radical prostatectomy specimens correlates with lymph node metastasis biochemical recurrence and distinct metastasis
bull Its presence in the needle biopsy is likely to have similar correlations
bull This feature is very rarely seen in needle biopsy specimens and should be reported only in needle biopsy specimens if properly identified
bull IHC (iexclCD34iexcl)
bull Triptocare lt5
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Site of sampling (specific location of the biopsy)
bull While obtaining multiple systematic biopsies is relatively standard in urologic practice the submission of needle cores in two containers (left and right side) or individual containers for each site [site-specific labeling (eg right apex right mid right base etc)] remains a matter of urologistinstitutional preference
bull Prognostic importance
bull Tumor involvement of base biopsies may influence bladder neck-sparing radical prostatectomy
bull extensive cancer in base biopsies correlates with extraprostatic extension
bull dominant side of prostate biopsy correlates with ipsilateral positivity of surgical margins and extraprostatic extension
bull Focal therapy
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Table 1101 Key features of three commercialized genomic tests for prostate cancer
Decipher OncoType Dx Prolaris
Gene panel 22 RNAs from diferente
regions of genome
12 cancer-related to
different pathways plus
5 reference genes
46 RNAs expression
signature
Tissue tested RP (pT3 margin+ or
rising PSA)
Biopsy very-low-to-
intermediate risk
Biopsy or RP
Utility Predicts probability of
metastasis 5 years after
RP
Predicts likelihood
of favorable pathology
Cell cycle progression
score for mortality or
biochemical recurrence
Tissue requirements 1 times 10-mm diameter
punch of highest
Gleason grade in FFPE
block
6 times 5-μ sections (10
mm length) + two HampEs
5 times 5-μ sections (05
mm length) + two HampEs
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
PROGNOSTIC MORPHOLOGIC FACTORSLopez-Beltran Montironi et al VA 2006
bull Grading according to the Gleason scheme and prognosticgrade groups (GG)
bull Other prognostic factorsbull Amount of tumor in prostate needle cores
bull Local invasion Extraprostatic extension and seminal vesicleinvasion
bull Perineural invasion
bull Lymphovascular invasion
bull Site of sampling (specific location of the biopsy)
bull Basic reporting of prostate biopsies
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
standardized (synoptic) reporting
bull The morphological findings of the needle biopsymay be placed into one of the following fivecategories
bull Prostate cancer
bull Atypical small acinar proliferation
bull High-grade prostatic intraepithelial neoplasia
bull Inflammation
bull Benign prostatic tissue
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Needle biopsy report
bull When carcinoma is not present
Boccon-Gibod et al 2004
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
Needle biopsy report
bull When carcinoma is presentbull Diagnosisbull Gleason score (and GG)bull Number (+) coresbull tissue with cancer
bull Linear measurement in mm (totallongest single length)
bull Perineural invasionbull Status adipose tissuebull High-grade PIN
bull Focalmultifocal
THANKS
THANKS
