Fertility Sparing in Gynecological Cancers Melkeet singh Department of O & G

Fertility Sparing Surgery in Gynecological Cancers Most common gynaecological cancers in reproductive age group includes - Cervical Cancer - Endometrial Cancer - Ovarian Cancer

Incidence of Gynaecological cancer in Reproductive age group. Incidence for (age < 49 year) /100000 Cervical Cancer 1.5-14.9/100000 Endometrial cancer 1.2-24 /100000 Ovarian Cancer 1.6-16.6 /100000

Mean age of First Time Mothers 40% of first time births occurs beyond age of 30. Among the reproductive age group, those beyond age of 30 are at greater risk of malignancy - which can jeopardize fertility. Need for fertility Sparing Surgery.

Cancer Treatment Objective Fertility Impaired Adverse Effects Psychological effects Cosmetic problems Loss of organ function Sexual and reproductive dysfunction Cure Fertility Impaired

Goals / Objectives of FSS Preservation of reproductive potential Preservation of hormonal function Similiar outcomes to standard therapy Favorable obstetric outcome Benefits > risk

FSS - Counseling Patient & family aware of the problem. Aware that they are assuming an undefined risk. Aware of limited data on the options. Options are not standard Therapeutic approaches. Patient must be extremely compliant with follow up. Once fertility completed, definitive procedure considered

FSS – Prerequisites Realistic probabilities of achieving conception based on age, history and infertility evaluation Desire to preserve fertility Tumor factors-histologic type, grade. Availability of ART

Nodes positive → Radiotherapy Abnormal smear → Colposcopy + Biopsy → Cone Biopsy No lesion CIN Microscopic CaCx Horizontal ≤7mm + Invasion < 3 mm ≤ 7mm + Invasion 3-5 mm >7mm > 5 mm 1A1 1A2 1B1-11A LVSI - LVSI + RH + PLND TAHBSO Intracavitary RT Modified RH +PLND RT Fertility desired CONE + PLND Trachelectomy + PLND Fertility desired CONE Enough. In selected cases if fertility desired - Trachelectomy + PLND 1A1- LN mets 0.5% Recurrence 2% LVSI 8-29% 1A2 LN mets 6-14% Recurrence 4% LVSI 53% Nodes positive → Radiotherapy

Stage 1A1 – Squamous Carcinoma A loop cone excision of the cervix is sufficient treatment .

Adenocarcinoma Skip lesions can occur ? Just Pre-invasive

NO EFFECT 18% PROM Cone – Fertility & Pregnancy Outcome (Clin. Exp. Obstet. Gynecol, 1992: 19(1):40-2) NO EFFECT Frencezy A, 1995 Haffenden DK, 1993 Tan L, 2004 < 15 mm 25% PRETERM LABOR 18% PROM Sadler L. Et al., Am J Med Ass, 2004 > 15 mm

Trachelectomy Abdominal / Vaginal Nodes must be assessed prior to procedure via frozen section Includes resection of the cervix + upper 2-cm of vagina + parametrium, with preservation of the uterine corpus. The uterine corpus is then sutured to the upper vagina. Cervical Circulage

Trachelectomy - Criteria A desire for fertility. No documentation of infertility. A proven diagnosis of cervical cancer Stage IA2 disease to stage IB1 disease Tumor limited to cervix. Tumor less than 2 cm No evidence of nodal metastases. Limited endo cervical involvement - Upper endocervical margins free of tumour (Frozen section) & MRI

Trachelectomy -Results Meta-analysis Dargent (Lyon) 82 Plante and Roy (Quebec) 44 Covens (Toronto) 58 Shepherd (London, UK) 40 Total 224 Recurrences 9(5.8%) Recurrences in Radical hysterectomy 4.4% 5 years survival in both group 97% Pregnancy Outcome Procedure 315 Documented 114 pregnancies in 97 patients Live births 93 Fertil Steril 2005;84:156

Preserving Fertility in Endometrial Cancer 2% -14 % of endometrial cancer  40 years Up to 25% PCOS G1 Early stage Respond to progestin treatment

Preserving Fertility in Endometrial Cancer Early Stage Ca Endo (Ia, G1) Standard treatment TAH + BSO +/- PLND Is there a fertility sparing surgery for cancer endometrium ?.

FSS in Endometrial Cancer I. Mazzon, et al (2010) described a three-step Technique , each characterized by a pathologic analysis. (1) removal of the tumor, (2) removal of endometrium adjacent to tumor (3) removal of the myometrium underlying the tumor. Followed by megestrol acetate 160 mg/day x 6 /12 Biopsies at 3, 6, 9, and 12 months were negative 4/6 (66%) achieved childbearing. I. Mazzon, G. Corrado, V. Masciullo, D. Morricone, G. Ferrandina, and G.Scambia “Conservative surgical management of stage IA endometrial carcinoma for fertility preservation,” Fertility and Sterility, vol. 93, no. 4, pp. 1286–1289, 2010.

Conservative Management Endometrial Cancer Criteria Patient and family aware of the possible risk Nulliparous Status. History (infertility ) Histology type- Endometroid type. Clear cell and UPSC excluded . Grade 1 malignancy. Tumour size Myometrial invasion excluded. ART facilities available After single delivery –hysterectomy

Complex Atypical Hyperplasia Precursor to cancer. Commonly detected in patients with PCOS. 30-60 % of hysterectomy performed for CAH are found to have frank malignancy. Standard recommendations is hysterectomy. Fertility preservation -hormonal therapy is an option after formal D&C

Hormonal therapy No consensus on type, dosage, duration, frequency, route and maintainance therapy Hormonal Therapy Endometrial Hyperplasia Endometrial Cancer With out Atypia With Atypia Medroxyprogestrone Acetate 10-30 mg PO 100 mg PO 400-800 mg in divided dose daily Megestrol Acetate 40 mg PO 160 mg PO Depo-Provera Mirena coil Various dosages used in trials

Endometrial Cancer Literature Overview (1961-2003) Patients = 81 62 (76%) responded Median time to response 12/52 (range 4-60/52) 15(24%) recurrence 7 retreated with hormones -5 responded. 20 patients conceived - 12 by ART 31 life births. ( some conceived more than once) Ramirez PT, Frumovitz M, Bodurka DC et al. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol 2004;95:133–138.

Preserving Fertility in Epithelial Ovarian Cancer Standart treatment TAH BSO + Omentec + append + PLND + PAND + washings + peritoneal biopsies Fertility Sparing Surgery Preserve Uterus and contra-lateral Ovary 118 early ovarian cancers that appeared to have disease limited to one ovary were however subjected to full staging. 3/118 (2.5%) of contra-lateral ovary were found to have microscopic disease. This risk must be conveyed to patients concerned. ( Bejamin et al)

FSS-Epithelial Ovarian Cancer Histology type Endometroid, Mucinous, Serous (Clear cell excluded) Stage 1A Grade 1 and possibly 2. After completion of fertility residual ovary and uterus should be taken out

Invasive Epithelial Ovarian Cancer Modified Staging Histology Stage IA G1 Stage IA G2, G3 Stage IC-III Selected cases requested by patients No further treatment Chemotherapy Chemotherapy

Chemotherapy and Fertility Premature ovarian failure after chemotherapy is more common with alkylating agents cyclophosphamide ( upto 68%) Ovarian failure less common with taxol and carboplatin (15-25%)

Epithelial Ovarian Cancer Treatment with Fertility-Sparing Therapy Stage IA and IC epithelial ovarian cancer 1965 to 2000, n=52 20 (%38) received chemotherapy 9 (17%) eventual TAH 5(10%) recurred, 2 died 24 (46%) attempted, 17 (33%) conceived 26 term Schilder et al., Gynecol Oncol, 2002

Germ Cell Tumors of the Ovary Age - first and second decade Usually unilateral Highly chemo sensitive to BEP Even advance stage responds well Fertility preserving surgery is the norm A Report of 28 germ cell / Cancer 42, 1152-1160 - 26 received chemotherapy except two with stage I immature teratoma. - 7 of 12 married patients, became pregnant, all had term delivery.

Borderline ovarian tumour Oophorectomy is not necessary if the initial operation was a cystectomy Surgical staging is not indicated Risk of recurrence- 6% for ipsilateral ovary ,3% for contralateral ovary and 3% for bilateral recurrence 5 Years survival 95-97% Recurrence higher in those with fertility sparing surgery but survival is similar to those who had a TAHBSO.

Border-line Tumors of the Ovary Conservative Management and Pregnancy Outcome Cancer 1998 Jan, 1;82(1):141-6 Retrospective review 82 patients 39 patients conservative management Three patients contralateral recurrence (7%) 22 pregnancies were achieved.

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Cancer Treatment Objective Fertility Impaired Adverse Effects Psychological effects Cosmetic problems Loss of organ function Sexual and reproductive dysfunction Cure Fertility Impaired