2. Gynaecological tumours Prof.Dr.Póka Róbert

3. Female genital cancer incidence (N/100.000 population/year) in 2008 Eurostat, 2010 EURHU Breast88,478,7 Cervix12,819,5 Endometrium16,717,7 Ovary13,713,7

4. Female genital cancer mortality (N/100.000population/year) in 2008 Eurostat, 2010 EURHU Breast24,322,6 Cervix5,25,7 Endometrium3,83,6 Ovary7,98,3

6. 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

7. Indications and types of surgical treatment Preserve fertility Preserve fertility Classical Wertheim-Meigs operation Classical Wertheim-Meigs operation Neoadjuvant chemo followed by radical surgery Neoadjuvant chemo followed by radical surgery Surgery for recurrent disease Surgery for recurrent disease

8. Trachelectomy’s necessity Changing morbidity Changing morbidity Changing demography Changing demography Changing technology Changing technology

9. Prerequisites of trachelectomy Ca.cx.ut. Std. Ia1,Ia2,Ib1 Ca.cx.ut. Std. Ia1,Ia2,Ib1 Parametrial spread excluded by CT, MR Parametrial spread excluded by CT, MR Fitness for surgery Fitness for surgery Fertility preservation is desired Fertility preservation is desired

11. Trachelectomy cases I. IDAgeStg ThFollow-up grav. 1. 31Ib1 (12*3mm)VTR 2x delivery (SC) 2. 28Ia1 (7*2mm)VTR+LND1x deliver (SC) 3. 25Ia2 (7*3mm)VTR+LND1x deliver (SC) 4. 34Ib1 (12*7)VTR+LND1x deliver (SC) 5. 36Ia2 (5*3) VTR(R1)TAH+LND TR: trachelectomy LND: lymphadenectomy

12. Trachelectomy cases II. IDAgeStg ThFollow-up 6.34Ia1 (3*1mm)VTR 61mths NED 7. 7. 36Ib1 (12*8mm)VTR+LND N1! 41mths NED 8. 8. 34Ib1adenoATR(R1N1)WM 23mths DOD 9. 9. 30Ia1adenoATR+LND39mths NED 10. 10. 34Ib1ATR(N1)WM 25mths DOD 11. 11. 30Ib1ATR+LND17mthsNED TR: trachelectomy LND: LSC lymphadenectomy

13. Aims of neoadjuvant chemoterapy Prevent spread Prevent spread Down-staging Down-staging Tumour-demarcation Tumour-demarcation

14. Modes of administration Monotherapy or combined chemotherapy Monotherapy or combined chemotherapy Cyclical Cyclical Systemic or regional Systemic or regional

15. Mechanism of action AlkilatingCytoxan,Ifosfamid AlkilatingCytoxan,Ifosfamid AntimitoticVincristin, Taxol AntimitoticVincristin, Taxol AntimetabolitesMethotrexat, Fluorouracil AntimetabolitesMethotrexat, Fluorouracil AntibioticsBleomycin, Mitomycin, Adriamycin, Peplomycin AntibioticsBleomycin, Mitomycin, Adriamycin, Peplomycin Anticytosceletal Taxanes Anticytosceletal Taxanes OtherCisplatin, Carboplatin OtherCisplatin, Carboplatin

16. Side-effects Immediateendothel necrosis Immediateendothel necrosis Earlynausea, vomiting, emesis, myelodepression Earlynausea, vomiting, emesis, myelodepression Latealopecia,myelodepression,mucositis, fibrosis pulmonum, neuritis, diarrhoea,insuff.hepatorenalis, cardiomyopathy Latealopecia,myelodepression,mucositis, fibrosis pulmonum, neuritis, diarrhoea,insuff.hepatorenalis, cardiomyopathy

17. Protocol BIPBleomycin 30mg/12hrs 1.day BIPBleomycin 30mg/12hrs 1.day CDDP 50mg/m2 2.day Ifosfamid 3 g/m2 3.day Mesna 1g/m2 3* 3-weekly

18. Neoadjuvant BIP chemoterapy at 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 = 21 Adenoca = 2, Planocell = 21 pTy0N0M0=7 pTy0N0M0=7 pTy1-3N1M0=6 pTy1-3N1M0=6

19. Female genital cancer Incidence (n/100000/yr) in 2008 Eurostat, 2010 EURHU Breast88,478,7 Cervix12,819,5 Corpus16,717,7 Ovary13,713,7

20. Female genital cancer Mortality (n/100000/yr) in 2008 Eurostat, 2010 EURHU Breast24,322,6 Cervix5,25,7 Corpus3,83,6 Ovary7,98,3

21. Gynecologic tumors Staging in general Ilocalized to organ of origin IIspread to adjacent tissues IIIregional lymphatic spread IVdistant metastasis

22. Endometrial cancer in Hungary in 2005 1213 new cases 219 deaths

23. Corpus cancer - Origin Endometrial cancer Endometrial cancer Endometrial stroma sarcoma Endometrial stroma sarcoma Myometrial sarcoma Myometrial sarcoma

24. Gynecologic tumors Staging in general Ilocalized to organ of origin IIspread to adjacent tissues IIIregional lymphatic spread IVdistant metastasis

25. Endometrial cancer stage-distribution (%)

26. Age distribution in endometrial cancer N=817

27. Histologic type distribution Endometrioid82 % Adenosquamous6 % Mucinous1% Papillary serous4 % Clear cell2 % Squamous0,5 % Other4,5 %

28. Pathogenesis Estrogen-dependent proliferation Estrogen-dependent proliferation Lack of gestogen-suppression Lack of gestogen-suppression Insulin-resistance Insulin-resistance Tumorsuppressor-mutations (p53,p21) Tumorsuppressor-mutations (p53,p21) Extragonadal aromatase-activity Extragonadal aromatase-activity

29. Characteristic associated disorders and medical history Hypertension Hypertension Diabetes mellitus Diabetes mellitus Obesity Obesity PCO PCO Anovulatory cycles Anovulatory cycles Less pregnancies Less pregnancies Shorter lactation Shorter lactation

30. Diagnosis Histologic verification

31. Prognostic factors in endometrial cancer Age Age Histologic type Histologic type Degree of differentiation Degree of differentiation Depth of myometrial invasion Depth of myometrial invasion Cervical involvement Cervical involvement Adnexal involvement Adnexal involvement Lymphatic spread Lymphatic spread Distant metastasis Distant metastasis

32. Pathologic staging (changes in 2010) IaLocalized to endometrium Ib (Ia)Superficial myometrium-invasion Ic (Ib)Deep myometrium-invasion IIa (Ib)Spread to cervix mucosa IIb (II)Cervical stromal involvement IIIaAdnex/serosa involvement IIIbVaginal metastasis IIIc (IIIc1/IIIc2)Pelv./paraaort. nodal metastasis IVaBladder/rectum invasion IVbDistant metastasis

33. I II (FIGO 2010) IB (FIGO 2010) IA (FIGO 2010) IIIc2 (FIGO 2010) IIIc1 (FIGO 2010)

37. Treatment Surgery (TAH+BSO+lymphadenect) Surgery (TAH+BSO+lymphadenect) Radiotherapy (adjuvant or primary) Radiotherapy (adjuvant or primary) Chemotherapy (adjuvant or primary) Chemotherapy (adjuvant or primary) Gestogen therapy (adjuvant) Gestogen therapy (adjuvant)

38. Five-year survival Surgery84% Radiotherapy45,3% Radiosurgery83,6% Surgery+Radiotherapy82,4% Surgery+Chemotherapy59,8% Hormonal therapy42,9%

39. Prevention Combined oral contraceptives >10yrs Combined oral contraceptives >10yrs Bodyweight control Bodyweight control Oncological surveillance Oncological surveillance Progestogenic opposition Progestogenic opposition

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

41. Endometrial cancer young cases All cases 1368 Age <45 yrs96 Age <45 yrs without hysterectomy6

42. Endometrial cancer cases at UD MHSC without hysterectomy IDAgeStg ThGravFollow-up 1. 27IaG1 6*CuP2 25yrs PD 2. 43IaG1 2*Cu08yrs NED 3. 29IIG1 Cu+2*IC024yrs ov.ca.III/b 4. 25IaG1 Cu+5*IC04yrs PCOD 5. 30IaG1 Cu+MPA02yrs NED 6. 23IaG1 Cu+MPA01yr NED

43. Ovarian cancer Epidemiology Epidemiology Incidence, mortality Incidence, mortality Staging Staging Diagnostic work-up Diagnostic work-up Debulking surgery (pathological staging) Debulking surgery (pathological staging) Adjuvant chemotherapy Adjuvant chemotherapy Neoadjuvant chemotherapy Neoadjuvant chemotherapy

46. Vulval carcinoma, Epidemiology Disease of the elderly Disease of the elderly 2-3% of all genital cencers 2-3% of all genital cencers In Hungary 122 new cases in 1994, 205 in 2005 In Hungary 122 new cases in 1994, 205 in 2005 90% squamous 90% squamous

47. FIGO stages Ia<2cm, <1mm invasion Ia<2cm, <1mm invasion Ib 1mm invasion Ib 1mm invasion II>2cm II>2cm IIIurethra/vagina/perineum/anus involvement, unilateral inguinal met IIIurethra/vagina/perineum/anus involvement, unilateral inguinal met IVarectal/bladder involvement, bilateral inguinal met IVarectal/bladder involvement, bilateral inguinal met IVbdistant met IVbdistant met

48. TNM stages FIGOTNM FIGOTNM Ia1a00 Ia1a00 Ib1b00 Ib1b00 II200 II200 III1-30-10 III1-30-10 IVa1-320 IVa1-320 IVa40-20 IVa40-20 IVb1-40-21 IVb1-40-21

49. Macroscopic appearance Superficial5-15% Superficial5-15% Exophytic40% Exophytic40% Endophytic45% Endophytic45%

50. Spread 1. Inguinal and femoral lymph nodes 2. Cloquet/Rosenmüller nodes 3. Parailiac nodes

51. Evolution of surgical treatment Parré-Jones Parré-Jones Inguinali radiotherapy Inguinali radiotherapy <1 mm invasion warrants no nodal disease <1 mm invasion warrants no nodal disease Sentinel nodes Sentinel nodes Neville Hacker Neville Hacker

52. Progression free survival improved by lymphadenectomy Vulvectomy+lymphadenectomy - Vulvectomy

53. Overall survival improved by lymphadenectomy Vulvectomy+lymphadenectomy - Vulvectomy

57. Summary of treatment for vulval cancer Survival of vulval cancer with no spread to urinary or GI tracts is improved by adding lymphadenectomy to wide excision of primary tumour. Survival of vulval cancer with no spread to urinary or GI tracts is improved by adding lymphadenectomy to wide excision of primary tumour. Advanced or regional metastatic disease treated with radiotherapy Advanced or regional metastatic disease treated with radiotherapy Disseminated tumours require chemotherapy Disseminated tumours require chemotherapy