Fertility-sparing treatment in stage IA grade 2 endometrioid endometrial cancer: Outcomes of a standardized approach

Objective To evaluate oncologic and reproductive outcomes of fertility-sparing treatment in women with stage IA grade 2 endometrioid endometrial cancer (EEC) without myometrial invasion treated with a standardized protocol. Methods Consecutive women diagnosed with stage IA grade 2 EEC without myometrial invasion between June 2019 and August 2024 at a single tertiary center were treated with hysteroscopic resection followed by combined progestin therapy with oral megestrol acetate (MA) 160 mg/day and a levonorgestrel intrauterine device (LNG-IUD). Results Twenty-five patients were included; median follow-up was 33 (IQR 12–90) months and median age 34 years (IQR 20–41). Complete response (CR) was achieved in 100% (25/25), with 84% at 6 months. Median time to CR was 6 months (range 6–12). Fifteen patients (60%) attempted conception, and 8 (53.3%) achieved pregnancy. Three delivered at term, three pregnancies are ongoing, and two resulted in miscarriage. Recurrence occurred in 56.0% (14/25) with a median time of 16.6 months. Six patients underwent definitive surgery, while eight were successfully retreated conservatively and are disease-free. Overall, 24/25 (96%) showed no evidence of disease at last follow-up. Most tumors were mismatch repair proficient (95.4%), none p53-mutated, with high ER/PR expression. All tested cases harbored β-catenin mutations. No treatment-related complications were observed. Conclusions A standardized fertility-sparing approach combining hysteroscopic resection and progestins achieved effective and safe management in stage IA grade 2 EEC without myometrial invasion, with favorable reproductive outcomes. These findings support its use in carefully selected patients, although longer follow-up is needed.