1. Ali AYHAN, MD Baskent University School of Medicine Department of Obstetrics & Gynecology Division of Gynecologic Oncology Fertility Sparing Surgery (FSS) Gynecologic Oncology in

2. The Main Purpose of Cancer Therapy High cure Low morbidity High level quality of life (as a mood, sexuel life, cosmetic appearence, fertility preservation...)

3. All Therapeutic Modalities in Female Cancer are associated with infertility (radiation, radical surgery, chemo...)

4. Therefore Fertility saving surgery instead of radical in early stage selected gynecological cancers is performed by different centers

5. FSS Objectives similiar oncologic outcomes to standard therapy favorable obstetric outcome benefits > risks low morbidity and cost

6. Benefits-Risks of FSS Benefits Preservation of fertility Maintanence of endocrine function Risks Increase in probability of recurrence and death Additional surgery

7. The Main Requirement of FSS preserving of the uterus preserving at least one ovary

8. Fertility Saving Surgery Depends on Type and origins of tumor Stage, grade, histology Age, performance Fertility desire Previous infertility problems Close follow up

9. Indications for Fertility Saving Surgery All germ cell Sex cord stromal (early stage) Borderline ovarian tumor Invasive EOC Cervical Carcinoma Endometrial Carcinoma

10. Fertility Saving Surgery in Ovarian Tumors (EOC, BOT,MOGCT, Sex Cord Stromal) Comprehensive surgical staging Removal of affected ovary and tube Preservation of uterus and contralateral ovary Finally evaluation of normal appearing contralateral ovary* and endometrium (D&C)** * For occult metastases ** Endometrioid type of epithelial tumors

11. FSS in EOC 14% of EOC will occur under 40 years 25-30% of all EOC are early stage at the diagnosis Of these 62% will be stage I and IIa Not all, many of these desire to preserve fertility SO TODAY; PROBLEM IS SMALL

12. Indication for Fertility Sparing Surgery in EOC 1.Stage Ia, Grade 1 Stage Ia, Grade 2 (limited) 2.Stage Ic, Grade 3, Clear cell + Chemotherapy

13. Main Problems in FSS in EOC A)In preserved ovary 1) occult metastasis 2) relapse in spared ovary B) Is there any relationship between relapse, death and preservation of ovary, uterus or other risk factors C) Is there a place of complementary surgery after childbearing

14. Occult Metastasis in Normal Appearing Ovaries varies from 6-12% in old literature in the new literature, this figures are about 2.5% in stage I disease Gynecologic Oncology, 2008:110,345-353

15. Survival after FSS 5 yrs DFS8378 5 yrs OS9188 Gynecologic Oncology, 2008:110,345-353 IA* * rates are comparable for standart surgery IC*

16. Recurrence, Death and Pregnancy After FSS in EOC AuthorRecurrences Ovary / Total DeathsPregnancy Colombo (n=152) 11 /189 (5.9%)53 (35%) Brown (n=16) 2 / 22? Schilders (n=52) 3 / 5231/17 UK Study (n=56) 12%0? Colombo N et al IJGC 2005, Monk BJ, DiSaia PJ, IJGC 2005, Farthing A, BJOG 2006

17. Obstetric Outcome After Fertility Saving Surgery in EOC Author % PregnancyTerm Delivery Abort.EctopicAnomaly Colombo 1994 100 (25/25) 16420 Zanetta 1997 56 (20/36) 17420 Duska 1999 33.3 (2/6) 2010 Morice 2001 22.2 (4/18) 3100 Schilder 2002 71 (17/24) 26500 Total56.5 (68/109) 641450

18. 15% of all EOC15% of all EOC Young ageYoung age Early stageEarly stage 95% serous–mucinous95% serous–mucinous Overall survival 95%Overall survival 95% Fertility Sparing Surgery in Borderline Tumors of the Ovary: Bilaterality: serous (25–50%), mucinous (5–10%), mixed (21%)

19. BSO (very rare) USO Cystectomy Partial excision Cortical ovarian biopsy for cryopreservation Ovarian procedures in BOT

20. Adenexectomy0–20 Cystectomy12–58 Radical Surgery3–6 Invasive recurrence2 Invasive implant20 Recurrence Features in BOT Procedure Relapse (%) EJSO 35, 643 – 648; 2009

21. Ovarian Tumors of Low Malignant Potential Study No. Pts. Stage No. Pregn. Lim-Tam 1988 35IA-III8 Gotlieb 1998 39IA-III22 in 15 Morris 200043IA-III25 in 12 Zanetta 2001 189IA-III44 in 44 Morice 200144IA-III17 in 14 Rao 200538IA-III6 in 5 Boran 200562IA-III10 in 10

22. 5% of all ovarian neoplasm Young age Early stage Generally unilateral (Dysgerminoma 12%) Highly lethal until BEP…. FSS in MOGCTs

23. Fertility Sparing Surgery Full staging Removal of affected ovary Preserving the contraleral ovary Preserving of the uterus Chemo  In early and selected advanced stage +

24. The survival in FSS group is similar to standard surgery in MOGCTs (equivalent cure with USO vs BSO±TAH)

25. Pregnancy after surgery in MOGCTs Number of patientsPregnancy rate 29/3276 % 19/2095 % (Surg + Chemo) 16/2080 % (Surg + Chemo) 12/12100 % (Only surgery) Low et al, Zanette et al, Gerhenson et al

26. Obstetric Outcome in MOGCT Author % PregnancyTerm Delivery Abort.EctopicAnomaly Gershenson 1988 100 (12/16) 22000 Perrin 1999 ------ 8-- 0 Low 2000 95 (19/20) 16-- 0 Zanetta 2001 80 (16/20) 269--3 Tangir 2003 76 (25/33) 382--0 Total 87.75 (72/89) 1101103

27. Endometrial Cancer Most frequent Gyn. Cancer 25% premenopausal 5% under 40 age Type I good prognosis (PCOS) Grade I, EPR + Cure rate 95%

28. Pretreatment Evaluation History (infertility...) Physicial Examination TVUSG D&C Abdominopelvic/ endovaginal coil MRI Ca-125 Laparoscopic evaluation Staging Laparotomy Response to Progesterone or

29. Progestogenic Agents MPA 200-600 /mg/ day Megace 40-160 /mg/day IUD / Prog Response Rate Hyperplasia with Atypia83-94% End. Ca57-75.6% Duration of Treatment Range3-6 months Recurrence Hyperplasia with Atypia13% End. Ca11-50%

30. At young ageAt young age Well differantiated End. CaWell differantiated End. Ca Stage IA, Grade I-IIStage IA, Grade I-II Progestin therapyProgestin therapy Evaluation of endometrium with 3 months intervalEvaluation of endometrium with 3 months interval Fertility desireFertility desire FSS in Endometrial Cancer

31. FSS in Cervical Cancer 27.9% patients < 40 age (SEER) Cx Ca most prevalant in 35-39 years of age Adenocarcinoma is a problem Squam/ Adeno (except neuroendocrine type) IA-IB1* *Tumor < 2 cm, Deep Stromal Inv. < 1 cm

32. Preinvasive Ia1, LVSI (-) 1a1, LVSI (+) 1a2 1b1, 2 cm, depth 1 cm in selected cases with stage Ib-IIA ovarian transposition, oocyte and/or embryo criopreservation Pelvic LND* + Radical Trachelectomy** * Endoscopic / Laparotomy / Sentinel Node ** Vaginal / Abdominal Cone Only FSS in Cervical Cancer

33. IA1 LVSI (-) CONE Tumor free margin and post-cone negative ECC Positive margin or positive ECC RE-CONE

34. Stage IA1 with LVSI (+) IA2 Pelvic lymphadenectomy Radical trachelectomy* Cervical cerclage *Free margin >at least 5mm-1 cm +

35. Why lymphadenectomy in Stage IA2 ? VariablesLNM Metas. (%) LNM (+) 7.3 Invasive Rec 3.1 DOD 2.3 Van Nagell et al, Creasman et al

36. Removal of primary tumor Parametrectomy 1/3 upper vaginectomy Preserving uterine fundus Pelvic lymphadenectomy Radical trachelectomy (1994 Dargent)

37. Abdominal Vaginal Lymphadenectomy (Open or Endoscopic ) Radical trachelectomy

38. Obstetric Outcome in RVT (pregnancies: 256) TAB / EUP145 1 st trimester loss4718 2 nd trimester loss228 3 rd trimester delivery15862 < 32 wks delivery1812 33–36.6 wks delivery2616 > 37 delivery10265 #% Gynecol Oncol. 2010 May;117(2):350-7 Fertility-sparing options for early stage cervical cancer. Gien LT, Covens A Gynecol Oncol. 2008; 111(S):105-110 Vaginal radical trachelectomy: An update. Plante, M

39. Gynecol Oncol. 2010 May;117(2):350-7 Fertility-sparing options for early stage cervical cancer. Gien LT, Covens A RVT, Oncologic Outcome tumor size ≥ 2cm LVSI [(12% (+) vs 2% (-)] unfavorable histology recurrence rate 4.2–5.3% mortality rate 2.5–3.2% Risk Factors for Recurrences

46. Fertility Preservation Options in Females Conservative surgery Embryo cryopreservation Oocyte cryopreservation Ovarian tissue cryopreservation Ovarian supression (GnRH analogs)

47. Thank you for your attention