Integrating molecular classification into endometrial cancer management

Endometrial carcinoma is biologically heterogeneous. Molecular classification derived from The Cancer Genome Atlas (TCGA) identifies clinically relevant molecular subtypes, each with distinct prognostic and therapeutic implications. FIGO 2023 recognizes tumor biology in staging, and the new 2025 ESGO guidelines incorporate molecular data into risk-stratified management. This is a position paper on the incorporation of molecular classification in endometrial cancer. We focused on molecular taxonomy, diagnostic surrogates, prognostic validation, and therapeutic implications of immune and targeted agents. The five molecular subtypes (POLEmut; MMRd/MSI-H; p53abn; NSMP ER-positive; NSMP ER-negative) provide stronger prognostic discrimination than grade or histotype alone. We recommend that molecular subtype should guide adjuvant treatment de-escalation or intensification, inform the use of immunotherapy and targeted agents, and refine risk stratification beyond conventional parameters. We also discussed implementation challenges, including test standardization, reporting, equity of access, and areas of ongoing uncertainty. This position paper aims to support consistent, equitable, and biologically informed management of endometrial carcinoma in contemporary practice.