Updates on molecular classification and treatment in endometrial cancer

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries, with a steadily rising global incidence. The Cancer Genome Atlas (TCGA) study identified four molecular subtypes- POLE (ultramutated), MSI (hypermutated), copy number low, and copy number high-each with distinct prognostic and therapeutic implications. Integration of molecular classification into the WHO 2020 classification and the FIGO 2023 staging system has transformed clinical practice. Although major European ESGO/ESTRO/ESP guidelines now incorporate molecular subtyping into treatment algorithms, the Japanese JSGO 2023 guidelines have not yet formally integrated molecular classification into adjuvant treatment decisions. Notable differences exist between Japanese and Western approaches, particularly regarding the role of adjuvant radiation therapy versus chemotherapy. Recent landmark trials have provided compelling evidence for biomarker-driven treatment based on molecular classification. Furthermore, some immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) are emerging as promising therapeutic options. This review provides an updated overview of the molecular classification of EC, its impact on current guidelines with emphasis on radiation therapy, and the latest therapeutic advances including immunotherapy and ADCs.