Adjuvant Therapy for Endometrial Cancer in the Era of Molecular Classification

Endometrial cancer primarily undergoes surgical intervention, with adjuvant treatments such as external beam pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and combined therapy investigated in randomized trials. Treatment decisions hinge on clinicopathological risk factors. Low-risk cases usually require surgery alone, whereas high-intermediate risk often benefit from adjuvant vaginal brachytherapy for enhanced local control with minimal side effects. Recent trials advocate pelvic radiotherapy for high-risk cases, particularly in Stage I-II tumors with risk factors. Chemoradiation proves advantageous for serous cancers and Stage III disease, improving recurrence-free, and overall survival. Molecular studies, notably the Cancer Genome Atlas project, identified four distinct molecular classes, transcending stages, and histological types. These molecular subtypes exhibit a stronger prognostic impact than histopathological characteristics, heralding a shift toward molecular-integrated diagnostics and treatments. Incorporating molecular factors into adjuvant strategies, including targeted therapies, marks a new paradigm in endometrial cancer management, underpinning ongoing research, and clinical trials. This review outlines current adjuvant approaches, underscores the emergence of molecular-integrated risk profiling, and touches on developments in targeted therapy.