Integrating molecular classification into endometrial cancer management

Area of Science:

• Gynecologic Oncology
• Molecular Pathology
• Cancer Genomics

Background:

• Endometrial carcinoma exhibits significant biological heterogeneity.
• The Cancer Genome Atlas (TCGA) molecular classification reveals clinically relevant subtypes.
• Recent guidelines (FIGO 2023, ESGO 2025) integrate molecular data into staging and management.

Purpose of the Study:

• To provide a position paper on incorporating molecular classification into endometrial cancer management.
• To review molecular taxonomy, diagnostic surrogates, prognostic validation, and therapeutic implications.
• To support consistent, equitable, and biologically informed clinical practice.

Main Methods:

• Review of molecular taxonomy and classification of endometrial cancer.
• Analysis of prognostic validation of molecular subtypes.
• Evaluation of therapeutic implications for immune and targeted agents.

Main Results:

• Five molecular subtypes (POLEmut; MMRd/MSI-H; p53abn; NSMP ER-positive; NSMP ER-negative) offer superior prognostic discrimination compared to grade or histotype.
• Molecular subtypes should guide adjuvant treatment decisions, immunotherapy, and targeted therapy selection.
• Conventional parameters are refined by molecular subtyping for risk stratification.

Conclusions:

• Molecular classification is essential for personalized endometrial cancer management.
• Implementation requires addressing challenges in standardization, reporting, and access.
• Biologically informed management improves outcomes and treatment equity.