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

Abstract

e17643 Background: Prognostic stratification of endometrial cancer has improved with the incorporation of molecular classification into staging. Although previous meta-analyses have assessed the impact of lymph node metastasis (LNM) in the management of endometrial cancer, these studies predate the 2023 FIGO molecular staging system and the widespread use of sentinel lymph node (SLN) mapping. It remains unclear how these advances affect LNM rates in modern surgical practice. Methods: We performed a systematic review and meta-analysis of studies reporting lymph node status according to TCGA/ProMisE molecular subtypes, including POLE-mutated, MMR-deficient, No Specific Molecular Profile (NSMP), and p53-abnormal tumors. A random-effects model was used to estimate pooled LNM proportions. Sensitivity and publication-bias analyses were conducted in prespecified subgroups comparing SLN mapping with lymphadenectomy (LAD). Results: Twenty-one studies encompassing 8,963 patients were included. The prevalence of LNM varied substantially across molecular subtypes. p53-abnormal tumors demonstrated the highest pooled LNM rate (24%, 95% CI 17–32%), followed by MMR-deficient (15%, 95% CI 11–20%) and NSMP tumors (10%, 95% CI 7–14%). POLE-mutated tumors had the lowest LNM rate (9%, 95% CI 6–14%). Findings were robust across leave-one-out sensitivity analyses. Importantly, LNM rates did not differ significantly between SLN and LAD cohorts across molecular subtypes. Conclusions: Molecular classification provides clinically meaningful prognostic information beyond traditional histopathological factors and is strongly associated with the risk of LNM in endometrial cancer. The marked difference in nodal involvement between POLE-mutated and p53-abnormal tumors supports a more tailored approach to surgical staging. These findings also validate the reliability of SLN mapping for molecular risk stratification, supporting its use as a standard staging strategy.