Promising survival prospects and immunotherapy potential in polymerase epsilon-mutated endometrial cancer: a comprehensive systematic review and meta-analysis unveiling future therapeutic opportunities
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: 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<0.0001). Patients with POLE mutations showed significantly improved progression-free survival (hazard ratio, 0.37; 95% confidence interval, 0.26-0.53; I2=0%) and overall survival (hazard ratio, 0.57; 95% confidence interval, 0.40-0.79; I2=41%). Most cases were early stage (International Federation of Gynecology and Obstetrics I-II, 86%), endometrioid type (84%), with low myometrial invasion (<50%, 56%), limited lymphovascular space invasion (25%), and low lymph node metastasis (29%). CONCLUSION: POLE mutations in endometrial cancer are associated with a favorable prognosis and show promising potential for immunotherapy. Molecular subtyping that incorporates POLE mutation status should be considered standard practice for risk stratification and treatment planning.
Source: Obstetrics & Gynecology Science
DOI: 10.5468/ogs.25179
Authors: Cut Adeya Adella, Felix Khosasi, Elbert Elbert
Institution: Universitas Sumatera Utara
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funder: Universitas Sumatera Utara
OpenAlex ID: W7130950534