Deciphering survival disparities in endometrial cancer: a focus on mismatch repair pathway integrity (systematic...

Endometrial cancer (EC) exhibits significant molecular heterogeneity, with mismatch repair deficiency (MMR-d) identifying a key subtype. While MMR-d is a known predictive biomarker for immunotherapy, its independent prognostic role remains debated. This systematic review and meta-analysis evaluates the association between MMR status and survival outcomes in EC.

A comprehensive search of PubMed, EMBASE, Web of Science, and ScienceDirect was conducted for studies published through July 1, 2025, reporting hazard ratios (HR) for survival based on MMR status. Pooled HRs and 95% confidence intervals (CIs) for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were calculated using random-effects models.

Sixteen high-quality studies encompassing 7486 patients (25.6% MMR-d) were included. MMR-d status was significantly associated with OS (pooled HR 1.25, 95% CI 1.02-1.53, $P < 0.001), though significant regional variation existed. Subgroup analysis revealed a survival benefit in Asian cohorts (HR 0.24, P = 0.02) but a trend toward poorer OS in European studies (HR 1.39, P = 0.05). No statistically significant associations were found for DSS (HR 1.22, P = 0.34) or PFS (HR 1.08, P = 0.04). Meta-regression indicated that follow-up duration did not moderate these outcomes.

MMR deficiency in EC is associated with variable survival outcomes heavily influenced by geographic and clinical context. While its independent prognostic value for DSS and PFS is limited, it remains a vital predictive biomarker for modern therapeutic stratification.