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Queen’s UniversityQueen’s UniversityQueen’s UniversityQueen’s University
QQueen’s University
ProstateProstate
D. Robert Siemens, M.D.D. Robert Siemens, M.D.
GU OncologyGU Oncology
Prostate CancerProstate Cancer– 20,700 cases, 4200 deaths (2006, CCS)20,700 cases, 4200 deaths (2006, CCS)
Bladder CancerBladder Cancer– 6400 cases, 1700 deaths6400 cases, 1700 deaths
Kidney CancerKidney Cancer– 4600 cases, 1550 deaths4600 cases, 1550 deaths
TestesTestes– 840 cases, 30 deaths840 cases, 30 deaths
Web ResourcesWeb Resources
http://cancernet.nci.nih.gov/http://cancernet.nci.nih.gov/cancertypes.htmlcancertypes.html
www.cancer.cawww.cancer.ca www.cua.orgwww.cua.org www.cancercare.on.cawww.cancercare.on.ca
ObjectivesObjectives
To be able to state the two components that To be able to state the two components that can cause bladder obstruction in benign can cause bladder obstruction in benign prostatic hyperplasiaprostatic hyperplasia
To be able to state 3 management options To be able to state 3 management options for early prostate cancerfor early prostate cancer
To understand the importance of the To understand the importance of the grading of prostate cancergrading of prostate cancer
Prostate DiseasesProstate Diseases
Benign Prostatic Hyperplasia (BPH)Benign Prostatic Hyperplasia (BPH)
Prostate CancerProstate Cancer
ProstatitisProstatitis
BPHBPH
Prostate size increases with ageProstate size increases with age
Total prostate volume increases from Total prostate volume increases from approximately 25 mL for a man in his 30s to 35–approximately 25 mL for a man in his 30s to 35–45 mL for a man in his 70s45 mL for a man in his 70s
Increased cell numbersIncreased cell numbers– Balance between cell proliferation and impaired Balance between cell proliferation and impaired
apoptosisapoptosis
BPHBPH
Hyperplasia of epithelial (glandular) or Hyperplasia of epithelial (glandular) or stromal (smooth muscle) componentsstromal (smooth muscle) components
Commonly cause lower urinary tract Commonly cause lower urinary tract symptoms in men (over 50)symptoms in men (over 50)– Relative obstruction of bladderRelative obstruction of bladder
BPH Risk FactorsBPH Risk Factors MaleMale AgingAging Androgens (testosterone, DHT)Androgens (testosterone, DHT) Androgen receptorAndrogen receptor Intraprostatic 5 alpha reductaseIntraprostatic 5 alpha reductase EstrogensEstrogens Apoptosis regulationApoptosis regulation Stromal-epithelial interactionsStromal-epithelial interactions Growth FactorsGrowth Factors
– bFGF, KGF, EGF, TGF-beta, IGFbFGF, KGF, EGF, TGF-beta, IGF
Static Dynamic
Increased muscle tone
BPH ComponentsBPH Components
Lower Urinary Tract Symptoms Lower Urinary Tract Symptoms (LUTS)(LUTS)
Obstructive (voiding)
Irritative(filling)
• Weak stream
• Hesitancy
• Sensation of incomplete emptying
• Intermittent stream
• Prolonged urination
• Frequency
• Nocturia
• Urgency
• Urge incontinence
Differential DiagnosisDifferential Diagnosis
Phimosis
Vesicosphincter dyssynergia
Bladder cancer
Stenosis of urinary meatus
Urethritis
Urethral carcinoma
Hypertrophy or stenosis of bladder neck
Cystolithiasis
Neurogenic
MyogenicCystitis
Bladder dysfunction (diabetes)
Polyuria
Extrinsic pelvic mass
BPH
Prostate Cancer
Urethral stricture
(Ouslander JG. Am J Med Sci 1997;314(4):214-8; Kasraeian A. www.dcmsonline.org; other references upon request)
-Blockers: Mode of Action-Blockers: Mode of Action
Relaxes prostate and bladder neck Relaxes prostate and bladder neck smooth-muscle tonesmooth-muscle tone
55-Reductase Inhibitors-Reductase Inhibitors
Block conversion of testosterone to dihydrotestosterone (DHT) within
the prostate
Transurethral Resection of Transurethral Resection of Prostate (Prostate (TURP)TURP)
Resectoscope Resectoscope
Bladder Bladder
Prostate Prostate
Removal of Removal of Hypertrophied Hypertrophied
TissueTissue
Prostate Cancer is Common!Prostate Cancer is Common!
13% lifetime risk of prostate cancer13% lifetime risk of prostate cancer
3% lifetime risk of dying of prostate cancer3% lifetime risk of dying of prostate cancer
Prostate Cancer is Common!Prostate Cancer is Common!
Most common cancer in men (27%)Most common cancer in men (27%)
18,200 new cases in 200218,200 new cases in 2002
4316 deaths in 20024316 deaths in 2002
1 death every 13 minutes1 death every 13 minutes
Roberts ‘99
Prostate Cancer IncidenceProstate Cancer Incidence
Risk factors?Risk factors?
MaleMale TestosteroneTestosterone AgeAge Others…..Others…..
– family history, race, diet etcfamily history, race, diet etc
Family History in Prostate Family History in Prostate CancerCancer
First degree relative affected ?First degree relative affected ?– NoNo RR= 1 xRR= 1 x– YesYes RR= 2-3 xRR= 2-3 x– Diagnosed <65Diagnosed <65 RR= 6 xRR= 6 x 3 relatives3 relatives RR= 11 RR= 11
xx
GENETICSGENETICS
HPC1HPC1
CAG repeatsCAG repeats
SDR5A2SDR5A2
VITAMIN EVITAMIN E
AntioxidantAntioxidant
Plant derived oilsPlant derived oils
Induces cell cycle arrest in PC-3 , LNCaPInduces cell cycle arrest in PC-3 , LNCaP
ATBC trialATBC trial
– 1/31/3rdrd reduced incidence @ 4 yrs reduced incidence @ 4 yrs– 41% reduced mortality @ 6 years41% reduced mortality @ 6 years
SELENIUMSELENIUM
Inconsistent dietary intakeInconsistent dietary intake
AntioxidantAntioxidant
Induces cell cycle arrest in LNCaPInduces cell cycle arrest in LNCaP
Clarke 1312 men with NMSCClarke 1312 men with NMSC
– 200 micrograms selenium as Brewer’s yeast200 micrograms selenium as Brewer’s yeast– 69 % reduced incidence of CaP69 % reduced incidence of CaP
SOYSOY
Japanese paradoxJapanese paradox
Isoflavones : Genistein / DaidzeinIsoflavones : Genistein / Daidzein– PhytoestrogensPhytoestrogens– Tyrosine kinase inhibitionTyrosine kinase inhibition– Induce apoptosis in PC-3Induce apoptosis in PC-3 // LNCaPLNCaP
DiagnosisDiagnosis
Digital rectal examinationDigital rectal examination PSAPSA
– Serine protease secreted into lumen of prostate glandsSerine protease secreted into lumen of prostate glands– Liquefies semenLiquefies semen– Elevated in BPH, prostate cancer, prostatitisElevated in BPH, prostate cancer, prostatitis
PSA test characteristicsPSA test characteristics– PSA 4-10 … cancer risk ~25%PSA 4-10 … cancer risk ~25%– PSA >10 … cancer risk ~50-60%PSA >10 … cancer risk ~50-60%
Prostate Cancer Stage Prostate Cancer Stage T1
incidental
T1a, T1b, T1c
T2
confined
T2a, T2b, T2c
T3
locally invasive
T3a, T3b, T3c
T4
fixation
T4a, T4b
Organ Confined Disease Treatment Organ Confined Disease Treatment OptionsOptions
Radical Surgery Radical Surgery
Radiation (ext beam and brachytherapy) Radiation (ext beam and brachytherapy)
Watchful Waiting Watchful Waiting
Advanced Prostate CancerAdvanced Prostate Cancer
Management of Advanced Prostate Management of Advanced Prostate CancerCancer
Use hormonal therapy to control Use hormonal therapy to control progressive or metastatic diseaseprogressive or metastatic disease
Charles HugginsCharles Huggins1901-19981901-1998
Awarded Nobel Prize in 1966Awarded Nobel Prize in 1966
Only Canadian-born doctor to win the Only Canadian-born doctor to win the Nobel Prize in Physiology or MedicineNobel Prize in Physiology or Medicine
CastrationCastration
Decrease prostate volumeDecrease prostate volume
Primary tumor shrinks (30-40%)Primary tumor shrinks (30-40%)
Metastatic deposits decrease (40-80%) and Metastatic deposits decrease (40-80%) and disappear (5-10%)disappear (5-10%)
Surgical CastrationSurgical Castration
Immediate and complete castrate levels Immediate and complete castrate levels (0.2 ng/ml) (0.2 ng/ml)
Adrenal androgens (5-10%)Adrenal androgens (5-10%)$1940$1940
Medical CastrationMedical Castration
LH-RH agonistsLH-RH agonists– suppression after initial flare of LH and Tsuppression after initial flare of LH and T
– castrate levels of T (0.2-0.5 ng/ml) in 9 days to castrate levels of T (0.2-0.5 ng/ml) in 9 days to 4 weeks4 weeks
– need to treat “flare” with antiandrogenneed to treat “flare” with antiandrogen
Medical CastrationMedical Castration
LH-RH agonistsLH-RH agonists– goserelin (Zoladexgoserelin (Zoladex®®), leuprolide (Lupron), leuprolide (Lupron®®), ),
buserelin (Suprefactbuserelin (Suprefact®®))
– depot injections 1 to 3-4 monthsdepot injections 1 to 3-4 months
$4500-8000/year$4500-8000/year
Adverse EffectsAdverse Effects
CastrationCastration– loss of libido and potency (>75%)loss of libido and potency (>75%)– hot flashes (50-60%)hot flashes (50-60%)– sweating (10%)sweating (10%)– painful gynecomastia (~1-2%)painful gynecomastia (~1-2%)– osteoporosis (5% fracture)osteoporosis (5% fracture)– cardiovascular effectscardiovascular effects– weight gain, loss of muscle massweight gain, loss of muscle mass
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