Prognostic Impact of POLE Exonuclease-Domain Mutations in Endometrial Cancer: A Systematic Review and Meta-Analysis

Cancer research · Endometrial cancer

The meta‑analysis revealed a significantly reduced risk of death in POLE‑mutant endometrial cancer patients, with an overall survival pooled hazard ratio (HR) of 0.35 (95% CI 0.21–0.58).

A systematic review and meta‑analysis of 20 observational studies (n = 7,708 endometrial cancer patients, 2.1 % POLE‑mutant) found that pathogenic/likely pathogenic POLE exonuclease‑domain mutations are associated with a markedly reduced risk of death (overall survival pooled HR = 0.35, 95 % CI 0.21–0.58). Disease‑free, progression‑free and recurrence‑free endpoints showed an even larger benefit (pooled HR = 0.22, 95 % CI 0.12–0.41). Cancer‑specific survival data were heterogeneous but generally favorable, often with zero events in POLE cohorts. These results support molecular risk stratification and potential treatment de‑escalation in patients with POLE‑mutant endometrial cancer.

POLE‑mutant endometrial cancers exhibit an ultramutated, highly immunogenic phenotype that confers an exceptionally favorable prognosis. Recognizing the robust survival benefit enables clinicians to identify low‑risk patients who may safely avoid overtreatment, thereby reducing morbidity and improving quality of life while guiding the design of future trials that exploit the unique biology of POLE‑mutated tumors.

Evidence level: Számítógépes vagy elméleti. Modellből vagy adatbányászatból származó jel.

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