Promising survival prospects and immunotherapy potential in polymerase epsilon-mutated endometrial cancer: a comprehensive systematic review and meta-analysis unveiling future therapeutic opportunities

OBJECTIVE: Mutations in the DNA polymerase epsilon (POLE) gene in endometrial cancer define a distinct molecular subgroup with therapeutic relevance. This study evaluates their prognostic significance to refine risk stratification and guide treatment planning, especially within immunotherapy-based approaches. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and was registered in the PROSPERO database (CRD420251064413). Cohort studies from 2018-2025 were retrieved from major databases. Study quality was assessed using the quality in prognostic studies tool. Hazard ratios for overall survival, disease-specific survival, and progression-free survival were synthesized using Review Manager 5.4 (Cochrane Collaboration, London, United Kingdom), and R statistical software 4.4.2 (R Foundation for Statistical Computing, Vienna, Austria) with heterogeneity assessed using the I-squared statistic and publication bias examined through funnel plots, Egger's test, and the Trim-and-Fill method. RESULTS: POLE mutations were identified in 9% of endometrial cancer cases (95% confidence interval, 9-11%; I2=90.6%; P