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.