Gynaecological tumoursGynaecological tumours

Prof.Dr.Póka RóbertProf.Dr.Póka Róbert

Female genital cancer Female genital cancer incidenceincidence

(N/100.000 population/year) (N/100.000 population/year) in 2008in 2008Eurostat, 2010Eurostat, 2010

EUREUR HUHU

BreastBreast 88,488,4 78,778,7

CervixCervix 12,812,8 19,519,5

EndometriumEndometrium 16,716,7 17,717,7

OvaryOvary 13,713,7 13,713,7

Female genital cancer Female genital cancer mortality mortality

(N/100.000population/year) (N/100.000population/year) in 2008in 2008Eurostat, 2010Eurostat, 2010

EUREUR HUHU

BreastBreast 24,324,3 22,622,6

CervixCervix 5,25,2 5,75,7

EndometriumEndometrium 3,83,8 3,63,6

OvaryOvary 7,97,9 8,38,3

Cervical cancer treatment dilemmas

•Early stg disease - Op, advanced - Rad•Rad limited by normal tissue tolerance•Clinically early might be biologically advanced•In early stg Op and Rad results are similar

Indications and types of Indications and types of surgical treatmentsurgical treatment

Preserve fertilityPreserve fertility Classical Wertheim-Meigs operationClassical Wertheim-Meigs operation Neoadjuvant chemo followed by Neoadjuvant chemo followed by

radical surgeryradical surgery Surgery for recurrent diseaseSurgery for recurrent disease

Trachelectomy’s necessityTrachelectomy’s necessity

Changing morbidityChanging morbidityChanging demographyChanging demographyChanging technologyChanging technology

Prerequisites of Prerequisites of trachelectomytrachelectomy

Ca.cx.ut. Std. Ia1,Ia2,Ib1Ca.cx.ut. Std. Ia1,Ia2,Ib1Parametrial spread excluded by CT, Parametrial spread excluded by CT, MRMRFitness for surgeryFitness for surgeryFertility preservation is desiredFertility preservation is desired

Trachelectomy cases I.Trachelectomy cases I.

IDID AgeAge StgStg ThTh Follow-up grav.Follow-up grav.1.1. 3131 Ib1 (12*3mm)Ib1 (12*3mm) VTRVTR 2x delivery (SC) 2x delivery (SC) 2.2. 2828 Ia1 (7*2mm)Ia1 (7*2mm) VTR+LNDVTR+LND 1x deliver (SC)1x deliver (SC)3.3. 2525 Ia2 (7*3mm)Ia2 (7*3mm) VTR+LNDVTR+LND 1x deliver (SC)1x deliver (SC)4.4. 3434 Ib1 (12*7)Ib1 (12*7) VTR+LNDVTR+LND 1x deliver (SC)1x deliver (SC)5.5. 3636 Ia2 (5*3) Ia2 (5*3) VTRVTR(R1)(R1)TAH+LNDTAH+LND

TR: trachelectomyTR: trachelectomyLND: lymphadenectomyLND: lymphadenectomy

Trachelectomy cases II.Trachelectomy cases II.ID Age Stg Th Follow-up 6. 34 Ia1 (3*1mm) VTR 61mths NED

7. 36 Ib1 (12*8mm) VTR+LND N1! 41mths NED

8. 34 Ib1adeno ATR(R1N1)WM 23mths DOD9. 30 Ia1adeno ATR+LND 39mths NED10. 34 Ib1 ATR(N1)WM

25mths DOD11. 30 Ib1 ATR+LND 17mthsNED

TR: trachelectomyTR: trachelectomyLND: LSC lymphadenectomyLND: LSC lymphadenectomy

Aims of neoadjuvant Aims of neoadjuvant chemoterapy chemoterapy

Prevent spreadPrevent spread Down-stagingDown-staging Tumour-demarcationTumour-demarcation

Modes of administrationModes of administration

Monotherapy or combined Monotherapy or combined chemotherapychemotherapy

CyclicalCyclical Systemic or regionalSystemic or regional

Mechanism of actionMechanism of action

AlkilatingAlkilating Cytoxan,IfosfamidCytoxan,Ifosfamid AntimitoticAntimitotic Vincristin, TaxolVincristin, Taxol AntimetabolitesAntimetabolitesMethotrexat, FluorouracilMethotrexat, Fluorouracil AntibioticsAntibiotics Bleomycin, Mitomycin, Bleomycin, Mitomycin,

Adriamycin, PeplomycinAdriamycin, Peplomycin Anticytosceletal Anticytosceletal Taxanes Taxanes OtherOther Cisplatin, CarboplatinCisplatin, Carboplatin

Side-effectsSide-effects

ImmediateImmediate endothel necrosisendothel necrosis

EarlyEarly nausea, vomiting, emesis, nausea, vomiting, emesis, myelodepressionmyelodepression

LateLate alopecia,myelodepression,mucositis,alopecia,myelodepression,mucositis,fibrosis pulmonum, neuritis, fibrosis pulmonum, neuritis, diarrhoea,insuff.hepatorenalis, diarrhoea,insuff.hepatorenalis,

cardiomyopathycardiomyopathy

ProtocolProtocol BIPBIP Bleomycin 30mg/12hrsBleomycin 30mg/12hrs 1.day1.day

CDDP 50mg/m2CDDP 50mg/m22.day2.day

Ifosfamid 3 g/m2Ifosfamid 3 g/m2 3.day3.dayMesna 1g/m2 3*Mesna 1g/m2 3*

3-weekly3-weekly

Neoadjuvant BIP Neoadjuvant BIP chemoterapychemoterapyat UD MHSCat UD MHSC

Ib2-IIb N=23 (out of 100 WM)Ib2-IIb N=23 (out of 100 WM) Mean age 50 yrs (33-66)Mean age 50 yrs (33-66) Adenoca = 2, Planocell = 21Adenoca = 2, Planocell = 21 pTy0N0M0=7pTy0N0M0=7 pTy1-3N1M0=6pTy1-3N1M0=6

Female genital cancerFemale genital cancerIncidence (n/100000/yr) in Incidence (n/100000/yr) in

20082008Eurostat, 2010Eurostat, 2010

EUREUR HUHU

BreastBreast 88,488,4 78,778,7

CervixCervix 12,812,8 19,519,5

CorpusCorpus 16,716,7 17,717,7

OvaryOvary 13,713,7 13,713,7

Female genital cancerFemale genital cancerMortality (n/100000/yr) in Mortality (n/100000/yr) in

20082008Eurostat, 2010Eurostat, 2010

EUREUR HUHU

BreastBreast 24,324,3 22,622,6

CervixCervix 5,25,2 5,75,7

CorpusCorpus 3,83,8 3,63,6

OvaryOvary 7,97,9 8,38,3

Gynecologic tumorsGynecologic tumorsStaging in generalStaging in general

II localized to organ of localized to organ of originorigin

IIII spread to adjacent spread to adjacent tissuestissues

IIIIII regional lymphatic regional lymphatic spreadspread

IVIV distant metastasisdistant metastasis

Endometrial cancer in Endometrial cancer in Hungary in 2005Hungary in 2005

1213 new cases1213 new cases

219 deaths219 deaths

Corpus cancer - OriginCorpus cancer - Origin

Endometrial cancerEndometrial cancer Endometrial stroma sarcomaEndometrial stroma sarcoma Myometrial sarcomaMyometrial sarcoma

Gynecologic tumorsGynecologic tumorsStaging in generalStaging in general

II localized to organ of localized to organ of originorigin

IIII spread to adjacent spread to adjacent tissuestissues

IIIIII regional lymphatic regional lymphatic spreadspread

IVIV distant metastasisdistant metastasis

Endometrial cancer Endometrial cancer stage-distribution (%)stage-distribution (%)

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I II III IV

Frequency

Age distribution in endometrial Age distribution in endometrial cancercancer N=817N=817

05

1015202530354045

30 35 40 45 50 55 60 65 70 75 80 85 90

Age (yr)

N

Frequency

Histologic type distributionHistologic type distribution

EndometrioidEndometrioid 82 82 %%

AdenosquamousAdenosquamous 6 %6 %

MucinousMucinous 1%1%

Papillary serousPapillary serous 4 %4 %

Clear cellClear cell 2 %2 %

SquamousSquamous 0,5 %0,5 %

OtherOther 4,5 %4,5 %

PathogenesisPathogenesis

Estrogen-dependent proliferationEstrogen-dependent proliferation Lack of gestogen-suppressionLack of gestogen-suppression Insulin-resistance Insulin-resistance Tumorsuppressor-mutations Tumorsuppressor-mutations

(p53,p21)(p53,p21) Extragonadal aromatase-activityExtragonadal aromatase-activity

Characteristic associated Characteristic associated disorders and medical disorders and medical

historyhistory HypertensionHypertension Diabetes mellitusDiabetes mellitus ObesityObesity PCOPCO Anovulatory cyclesAnovulatory cycles Less pregnanciesLess pregnancies Shorter lactationShorter lactation

DiagnosisDiagnosis

Histologic verificationHistologic verification

Prognostic factors Prognostic factors in endometrial cancerin endometrial cancer

AgeAge Histologic typeHistologic type Degree of differentiationDegree of differentiation Depth of myometrial Depth of myometrial

invasioninvasion Cervical involvementCervical involvement Adnexal involvementAdnexal involvement Lymphatic spreadLymphatic spread Distant metastasisDistant metastasis

Pathologic stagingPathologic staging(changes in 2010)(changes in 2010)

IaIa Localized to endometriumLocalized to endometrium

IbIb (Ia)(Ia) Superficial myometrium-Superficial myometrium-invasioninvasion

IcIc (Ib)(Ib) Deep myometrium-invasionDeep myometrium-invasion

IIa IIa (Ib)(Ib) Spread to cervix mucosaSpread to cervix mucosa

IIb IIb (II)(II) Cervical stromal involvementCervical stromal involvement

IIIaIIIa Adnex/serosa involvementAdnex/serosa involvement

IIIbIIIb Vaginal metastasisVaginal metastasis

IIIc IIIc (IIIc1/IIIc2)(IIIc1/IIIc2) Pelv./paraaort. nodal Pelv./paraaort. nodal metastasismetastasis

IVaIVa Bladder/rectum invasionBladder/rectum invasion

IVbIVb Distant metastasisDistant metastasis

I

II (FIGO 2010)

IB (FIGO 2010)

IB (FIGO 2010)

IA (FIGO 2010)

IIIc2 (FIGO 2010)

IIIc1 (FIGO 2010)

TreatmentTreatment

Surgery (TAH+BSOSurgery (TAH+BSO++lymphadenect)lymphadenect) Radiotherapy (adjuvant or primary)Radiotherapy (adjuvant or primary) Chemotherapy (adjuvant or Chemotherapy (adjuvant or

primary)primary) Gestogen therapy (adjuvant)Gestogen therapy (adjuvant)

Five-year survivalFive-year survivalSurgerySurgery 84%84%

RadiotherapyRadiotherapy 45,3%45,3%

RadiosurgeryRadiosurgery 83,6%83,6%

Surgery+RadiotherapySurgery+Radiotherapy 82,4%82,4%

Surgery+ChemotherapySurgery+Chemotherapy59,8%59,8%

Hormonal therapyHormonal therapy 42,9%42,9%

PreventionPrevention

Combined oral contraceptives Combined oral contraceptives >10yrs>10yrs

Bodyweight controlBodyweight control Oncological surveillanceOncological surveillance Progestogenic oppositionProgestogenic opposition

Cases of endometrial cancer Cases of endometrial cancer at UD MHSC n=1368at UD MHSC n=1368

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90

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20 30 40 50 60 70 80 90 100AGE

Histogram

Endometrial cancer young Endometrial cancer young casescases

All casesAll cases 13681368

Age <45 yrsAge <45 yrs 9696

Age <45 yrs without hysterectomyAge <45 yrs without hysterectomy 66

Endometrial cancer cases Endometrial cancer cases at UD MHSC without at UD MHSC without

hysterectomyhysterectomy

IDID AgeAge StgStg Th Th GravGrav Follow-upFollow-up

1.1. 2727 IaG1IaG1 6*Cu 6*Cu P2 P2 25yrs PD25yrs PD

2.2. 4343 IaG1IaG1 2*Cu 2*Cu 00 8yrs NED8yrs NED

3.3. 2929 IIG1IIG1 Cu+2*IC Cu+2*IC 00 24yrs ov.ca.III/b24yrs ov.ca.III/b

4.4. 2525 IaG1IaG1 Cu+5*IC Cu+5*IC 00 4yrs PCOD4yrs PCOD

5.5. 3030 IaG1IaG1 Cu+MPA Cu+MPA 00 2yrs NED2yrs NED

6.6. 2323 IaG1IaG1 Cu+MPA Cu+MPA 00 1yr NED 1yr NED

Ovarian cancerOvarian cancer

EpidemiologyEpidemiology Incidence, mortalityIncidence, mortality StagingStaging Diagnostic work-upDiagnostic work-up Debulking surgery (pathological staging)Debulking surgery (pathological staging) Adjuvant chemotherapyAdjuvant chemotherapy Neoadjuvant chemotherapyNeoadjuvant chemotherapy

Vulval carcinoma, Vulval carcinoma, EpidemiologyEpidemiology

Disease of the elderlyDisease of the elderly 2-3% of all genital cencers2-3% of all genital cencers In Hungary 122 new cases in 1994, 205 in In Hungary 122 new cases in 1994, 205 in

20052005 90% squamous90% squamous

FIGO stagesFIGO stages

IaIa <2cm, <2cm, <<1mm invasion1mm invasion IbIb <2cm, >1mm invasion<2cm, >1mm invasion IIII >2cm>2cm IIIIII urethra/vagina/perineum/anus urethra/vagina/perineum/anus

involvement, unilateral inguinal metinvolvement, unilateral inguinal met IVaIVa rectal/bladder involvement, rectal/bladder involvement,

bilateral inguinal metbilateral inguinal met IVbIVb distant metdistant met

TNM stagesTNM stages FIGOFIGO TT NN MM IaIa 1a1a 00 00 IbIb 1b1b 00 00 IIII 22 00 00 IIIIII 1-31-3 0-10-1 00 IVaIVa 1-31-3 22 00 IVaIVa 44 0-20-2 00 IVbIVb 1-41-4 0-20-2 11

Macroscopic appearanceMacroscopic appearance

SuperficialSuperficial 5-15%5-15% ExophyticExophytic 40%40% EndophyticEndophytic 45%45%

SpreadSpread

1.1. Inguinal and femoral lymph Inguinal and femoral lymph nodesnodes

2.2. Cloquet/Rosenmüller nodesCloquet/Rosenmüller nodes

3.3. Parailiac nodesParailiac nodes

Evolution of surgical Evolution of surgical treatmenttreatment

Parré-JonesParré-Jones Inguinali radiotherapyInguinali radiotherapy <1 mm invasion warrants no <1 mm invasion warrants no

nodal diseasenodal disease Sentinel nodesSentinel nodes Neville HackerNeville Hacker

Progression free survival Progression free survival improved by improved by

lymphadenectomylymphadenectomy

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Overall survival improved Overall survival improved by lymphadenectomyby lymphadenectomy

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Vulvectomy+lymphadenectomy -

Vulvectomy

Summary of treatment for Summary of treatment for vulval cancervulval cancer

Survival of vulval cancer with no spread to urinary or GI tracts is Survival of vulval cancer with no spread to urinary or GI tracts is improved by adding lymphadenectomy to wide excision of improved by adding lymphadenectomy to wide excision of primary tumour.primary tumour.

Advanced or regional metastatic disease treated with Advanced or regional metastatic disease treated with radiotherapyradiotherapy

Disseminated tumours require chemotherapyDisseminated tumours require chemotherapy