Long-term outcomes of fertility-sparing treatment in endometrial carcinoma and endometrial intraepithelial neoplasia: Recurrence risk factors over a 9-year follow-up.

Abstract

Introduction: Fertility-sparing treatments using oral progestins have demonstrated promising oncologic outcomes for endometrial intraepithelial neoplasia and early-stage endometrial cancer. However, the high recurrence rate remains a major concern, and the literature on long-term follow-up outcomes is limited. This study aimed to identify recurrence risk factors by analyzing clinicopathological and molecular profiles in a cohort with a median follow-up of 9 years.

Material and methods: This retrospective study included patients under 45 years of age who were diagnosed with endometrial intraepithelial neoplasia or endometrial cancer and received fertility-sparing treatments at our center between 2010 and 2021. Patients who achieved complete responses were categorized according to recurrence status. Demographic, clinical, and molecular data were compared between groups. The primary endpoint was to identify risk factors for recurrence; secondary endpoints assessed obstetric and oncologic outcomes in patients with relapse.

Results: Out of 40 patients, 8 underwent hysterectomy within 1.5 years, while 32 responded to treatment and continued follow-up. The recurrence and non-recurrence groups contained 20 and 12 patients, respectively, with a median follow-up of 107.5 months (range, 35-175 months). Multivariate analysis showed that a family history of cancer (HR = 2.597, p = 0.039) and treatment with megestrol acetate as the initial therapy (HR = 3.130, p = 0.021) were independent risk factors for shorter time to recurrence. Although mismatch repair deficiency was positively correlated with recurrence, the association did not reach statistical significance (p = 0.057). Four out of 24 patients were upstaged after hysterectomy, and all were in the recurrence group. Nine patients (22.5%) achieved pregnancy, with three successfully conceiving after achieving complete response following retreatment.

Conclusions: In patients with long-term follow-up after fertility-sparing treatment, a family history of cancer and initial treatment with megestrol acetate were significantly associated with recurrence.