Molecular groups predict response to fertility-sparing treatment of endometrial carcinoma: a systematic review and metanalysis.

BACKGROUND: Molecular profiling has transformed endometrial carcinoma management, yet its value in predicting response to fertility-sparing conservative treatment remains undefined. OBJECTIVE: To provide pooled estimates of oncologic outcomes of fertility-sparing treatment in women with early-stage endometrioid endometrial carcinoma (EEC), stratified by molecular groups. DATA SOURCES AND SELECTION CRITERIA: Six electronic databases (MEDLINE, Google Scholar, Scopus, Web of Science, ClinicalTrials.gov, Cochrane Library) were searched from inception to December 2025. Peer-reviewed studies providing extractable data on oncologic outcomes of fertility-sparing treatment by molecular group in EEC women were included; literature reviews and case reports were excluded. MAIN OUTCOMES: Rates of complete response (CR), stable disease (SD), progressive disease (PD), and recurrence were pooled within each molecular group using a random-effects model with Freeman-Tukey transformation; heterogeneity was assessed with the I2 index, and risk of bias with MINORS. RESULTS: Nine studies were included and the pooled population comprised 295 conservatively treated EEC women (POLE-mt n = 23; MMRd n = 46; p53-abn n = 14; NSMP n = 212). Pooled CR was 95% in POLE-mt, 82% in NSMP, 62% in MMRd, and 41% in p53-abn groups. Pooled PD was 2%, 3%, 14%, and 38%, respectively. Pooled recurrence was 27% (POLE-mt), 26% (NSMP), 41% (MMRd), and 41% (p53-abn). CONCLUSION: In EEC women undergoing fertility-sparing management, molecular profiling might predict treatment response, with POLE-mt showing the best outcomes, p53-abn the worst, and MMRd and NSMP intermediate. If confirmed in larger cohorts, molecular profiling could be integrated into the pre-treatment workup to guide counselling. PROSPERO Registration Number: CRD420261322951.