Contemporary Fertility-Sparing Management Options of Early Stage Endometrioid Endometrial Cancer in Young Nulliparous Patients

Incidence of endometrial cancer (EC) has been increasing in recent years, especially in high-income countries. The disease commonly affects peri- and postmenopausal women; however, about 5% of women are diagnosed with EC in their reproductive age. Due to both the increasing incidence of EC among reproductive age women and trends to delayed childbearing, fertility-sparing treatment for young patients with EC has become extremely important for researchers and practitioners. Because the classic treatment with total hysterectomy and bilateral saplingo-oophorectomy is not an appropriate approach for young women demanding fertility preservation, several fertility-sparing options have been developed and summarized in this review. Utilization of different medications and their combination (progestagens, gonadotropin releasing hormones analogues, and metformin in different formulations) are tested and found as efficient for fertility-sparing treatment. New minimally invasive surgical techniques, combined with progestagens, are also confirmed as valuable. There are many novel conservative and surgical treatment approaches under investigation. Assuming that molecular biomarkers can be both diagnostic and prognostic to assist in prediction of response to a certain therapy, prognostic risk groups’ stratification along with specific biomarkers’ identification will ensure low recurrence and decrease mortality rates in young women with EC.

Conservative Surgery in Endometrial Cancer

Endometrial cancer (EC) is the sixth most common female cancer worldwide. The median age of diagnosis is 65 years. However, 4% of women diagnosed with EC are younger than 40 years old, and 70% of these women are nulliparous. These data highlight the importance of preserving fertility in these patients, at a time when the average age of the first pregnancy is significantly delayed and is now firmly established at over 30 years of age. National Comprehensive Cancer Network (NCCN guidelines state that the primary treatment of endometrial endometrioid carcinoma, limited to the uterus, is a total hysterectomy, bilateral salpingo-oophorectomy and surgical staging. Fertility-sparing treatment is not the standard of care, and patients eligible for this treatment always have to undergo strict counselling. Nowadays, a combined approach consisting of hysteroscopic resection, followed by oral or intrauterine-released progestins, has been reported to be an effective fertility-sparing option. Hysteroscopic resection followed by progestins achieved a complete response rate of 95.3% with a recurrence rate of 14.1%. The pregnancy rate in women undergoing fertility-sparing treatment is 47.8%, but rises to 93.3% when only considering women who tried to conceive during the study period. The aim of the present review is to provide a literature overview reflecting the current state of fertility-sparing options for the management of EC, specific criteria for considering such options, their limits, the implications for reproductive outcomes and the latest research trends in this direction.

Fertility-sparing surgery for patients with stage IC2 or IC3 epithelial ovarian carcinoma: any evidence of safety?

ObjectiveInvestigate the overall survival of patients with stage IC2/IC3 epithelial ovarian carcinoma undergoing fertility-sparing surgery.MethodsPatients aged <45 years diagnosed between January 2004 and December 2015 with epithelial ovarian carcinoma, who underwent surgical staging and had tumor involving the ovarian surface (IC2), malignant ascites or positive cytology (IC3), were identified in the National Cancer Database. The fertility-sparing surgery group included patients who had preservation of the uterus and the contralateral ovary while the radical surgery group included patients who had hysterectomy with bilateral salpingo-oophorectomy. Overall survival was evaluated following generation of Kaplan–Meier curves while a Cox model was constructed to control for tumor grade and performance of lymphadenectomy. A systematic review of the literature was performed and cumulative relapse rate among patients with IC2/IC3 disease who underwent fertility-sparing surgery was calculated.ResultsA total of 235 cases were identified; 105 (44.7%) patients underwent fertility-sparing surgery. There was no difference in overall survival between the fertility-sparing and radical surgery groups (p=0.37; 5- year overall survival rates 90.2% and 85%, respectively). After controlling for tumor grade and performance of lymphadenectomy, fertility-sparing surgery was not associated with worse overall survival (HR 1.22, 95% CI 0.56, 2.62). A systematic review identified 151 patients with stage IC2/IC3 disease who underwent fertility-sparing surgery. Cumulative relapse rate was 19.3% (n=29) while 12 (6.7%) deaths were reported. Median time to recurrence was 19 (range 1–128.5) months. Tumor recurrence involved the ovary exclusively in 42% (11/26) of patients, while 15% (4/26) had a lymph node, 35% (9/26) a pelvic/abdominal, and 8% (2/26) a distant tumor relapse.ConclusionsIn a large cohort of patients with stage IC2/IC3 epithelial ovarian carcinoma, fertility-sparing surgery was not associated with worse overall survival. However, based on a literature review, relapse rate is approximately 20%.

Analysis of the Safety and Pregnant Outcomes of Fertility-Sparing Surgery in Ovarian Malignant Sex Cord-Stromal Tumors: A Multicenter Retrospective Study

Background: To assess the difference in survival between fertility-sparing surgery (FSS) and radical surgery (RS) and explore pregnant outcomes after FSS in stage I malignant sex cord-stromal tumors (MSCSTs).Methods: We performed a multicenter retrospective cohort study on patients who were diagnosed with stage IA or IC MSCSTs. Inverse Probability of Treatment Weighting was performed between the FSS and RS groups. The Chi-square test and Kaplan-Meier method were used to compare the categorical variables and disease-free survival (DFS). The binary logistic regression analysis and Cox proportional hazards regression analysis were used to identify high-risk factors related to DFS and pregnancy.Results: A total of 107 patients were included, of whom 54 (50.5%) women underwent FSS, and 53 (49.5%) women underwent RS. After IPTW, 208 patients were obtained, and all of the covariates were well balanced. After a median follow-up time of 50 months (range 7-156 months), there was no significant difference of DFS between the two groups in both unweighted cohort (P=0.969) or weighted cohort (P=0.792). In the weighted cohort, stage IC (P=0.014), tumor diameter >8 cm (P=0.003), incomplete staging surgery (P=0.003) and no adjuvant chemotherapy (P <0.001) were 4 high-risk factors associated with a shorter DFS. Among 14 patients who had pregnancy desire, 11 (78.6%) women conceived successfully, and the live birth rate was 76.9%. In univariate analysis, only adjuvant chemotherapy (P=0.009) was associated with infertility.Conclusions: On the premise of complete staging surgery, FSS is safe and feasible in stage IA and IC MSCSTs with satisfactory reproductive outcomes.