Molecular subtypes and lymph-node metastasis in endometrial cancer: An updated systematic review and meta-analysis

Although prognostic stratification has improved with the use of molecular classification in endometrial cancer staging, it is still unclear how this will affect lymph-node metastasis in modern surgical practice. The objective of this meta-analysis was to update and refine pooled estimates of lymph-node metastasis prevalence across the molecular subtypes of endometrial cancer.

We performed a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines (PROSPERO: CRD420251276666). PubMed, Embase, and the Cochrane Library were searched through December 2025. Eligible studies reported lymph-node status based on TCGA/ProMisE molecular subtypes (POLE-mutated (POLEmut), mismatch repair-deficient (MMRd), no specific molecular profile (NSMP), p53-abnormal (p53abn)).

21 studies with 8963 patients were included. p53abn tumors showed the highest pooled lymph node metastasis rate (24%, 95% CI 17-32%), followed by MMRd (15%, 95% CI 11-20%) and NSMP tumors (10%, 95% CI 7-14%). POLEmut tumors consistently demonstrated low rates of nodal involvement (9%, 95% CI 6-14%). These findings were robust across leave-one-out sensitivity analyses. Pooled lymph-node metastasis rates were broadly similar between sentinel lymph node (SLN) and lymphadenectomy cohorts across molecular subtypes, although these comparisons should be interpreted cautiously.

Molecular classification provides clinically meaningful information beyond traditional histopathologic factors and is closely associated with the risk of lymph-node metastasis in endometrial cancer. The consistently low nodal involvement observed in POLEmut and the high risk observed in p53abn support a more tailored approach to surgical staging.