FERTILITY SPARING IN ENDOMETRIAL CANCER Prof. Dr. Bülent Özçelik Erciyes University Medical Faculty Department of Obstetrics and Gynecology Gynecologic Oncology Unit
Endometrial Cancer Most frequent gynecologic cancer Lifetime risk 2.81% Classically seen in postmenopausal period Approximately; 9% < 44 years of age 20% between 45 55 years Duska LR, Gynecol Oncol, 2001.
Risk Factors Increasing BMI Nulliparity infertility Chronic anovulation PCOS Increased rate of HNPCC mutations??
Standart Treatment Peritoneal cytology Histerectomy+BSO Lymph nod dissections Omentectomy
Fertility Sparing Options Partial Preservation Total Preservation Hysterectomy performed At least one ovary preserved Surrogate motherhood Uterus and ovaries preserved High dose progestines WL Lee, Taiwanese J Obstet Gynecol, 2012
Partial preservation; is it safe? n (totaly) n (recur) 5 y OS 10 y OS Oophorectomy 319 8 97.8% 91.3% Preservation 176 4 94.5% 94.5%
Synchronous Ovarian Cancer Incidence; 2 8% in SCEO, 5.1% in ECOM Tend to be low grade and early stage Ovarian member of SCEO frequently associated with endometriosis In endometrioid type, prognosis is better than other histologic types of ovarian cancer Ayhan A, Eur J Gynecol Cancer, 2003 Bese T, Int J Gynecol Oncol, 2016
Selection Criteria for Conservation (SGO Practice Bulletin Number: 149) Endometrioid type, well differentiated, G I tm No myometrial invasion No extra uterine disease (synchronous or metastatic) Strong fertility desire No contraindication for medical therapy Exact information about therapy and outcomes Erkanlı S, Ayhan A. Int J Gynecol Cancer, 2010
Young age and tumor characteristics Among the young patients eight (18%) had Tip I, Stage IA (no MI), Grade I disease
Recommended Methods for Assessment Dilatation and Curettage 10% of cases in D&C 26% of cases in office bx, upgraded at hysterectomy specimens Daniel AG, Obstet Gynecol, 1988 Larson DM, Obstet Gynecol, 1995
Recommended Methods for Assessment MRI, preferred modality for the evaluation of MI Accuracy Sensitivity Specificity US 69% 50% 81% CT 61% 40% 75% MRI 89% 90% 88% Kim SH, J Comput Assist Tomogr, 1995
Recommended Methods for Assessment Other optional interventions Laparoscopic staging PET CT for exclusion of nodal and ovarian metastases or concomitant ovarian tm Hormone receptor status
Treatment Options Surgical Medical Hysteroscopic resection Progestines (MPA, Megestrol acetate, IUS) Others (Aromatase inh., Tmx, GnRHa)
Hysteroscopic Resection Three step resection Step 1: Resection of tm Step 2: Resection of underlying myometrıum Step 3: Resection part of the end adjacent to the tm Mazzon I, Fertil Steril, 2010
Hysteroscopic Resection Preferential treatment is progestagenic therapy HS surgery prior to this may improve the outcomes Pregnancy outcomes is very limited This outcomes may be affected by endometrial damages Sonsoles A, ecancer, 2015
Hormonal Therapy Primary choose is progestines
MA and MPA are the most frequently evaluated treatment in the literature Both are antiestrogenic and antiandrogenic MA oral bioavailability is significantly higher MA with higher remission and lower progression probability MA can be a first line agent for fertility sparing manner Koskas M, Fertil Steril, 2014
What is the appropriate dose MPA 200 mg/day* Megestrol acetate 160 md/d (??) Thigpen JT, J Clin Oncol, 1999 Koskas M, Fertil Steril, 2014
Remision Probability of progestin therapies Months 3 6 12 18 24 Remission Rate 30.4% 72.4% 78% 80% 81% Koskas M, Fertil Steril, 2014
Recurrence probability after progestin therapies Months 4 6 12 18 24 Recurrence Rate 3.6% 9.6% 17.2% 26.0% 29.2%
Safety of Fertility Sparing in High Grade and Invasive Group N C. Response (%) Recurrence (%) Stage 1A G 2 3, no MI 17 76.5 23 (8 20 months) Stage 1A G 1, with SMI 23 73.9 47 (7 69 months) Stage 1A G 2 3, with SMI 8 87.5 71 (14 48 months) Park JY, Obstet Gynecol, 2013
Follow up Repeat endometrial sampling every 3 months while progestin therapy Choose of appropriate ART Recommend definitive surgey after complation of chidbearing or conservative option Ramirez PT, Gynecol Oncol, 2004 Ushijima K, J Clin Oncol, 2007
Pregnancy rate 111/351 (31.6%) Pregnancies 60 (54.1%) with ART 29 (26.1%) spontaneous 22 (19.8%) not clear Median age 32.1 (22 42 years)
47 patients enrolled 4 patients exluded due to incomplete data 43 patients analyzed 82% Complete response 18% No response 5% Recurrence or persistance during follow-up 39% Pregnancy (+) 61% Pregnancy (-) Hysterectomy performed Tumors were limited the uterine cavity IVF 60% Spontaneous 13% Spontaneous after ICSI 13% ICSI 7% IUI 7%
Conclusion Procedure is safe in low grade superficial tm Oncologic risks must be shared with patients Megestrol acetate should be the preferred treatment Close follow up is mandatory Persistent patients must be convinced to definitive surgery Treatment should be centralized
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