Adjuvant therapy guided by molecular classification in endometrial cancer: survival benefit and safety profile

To evaluate the effect of molecular classification-based postoperative adjuvant therapy on survival outcomes and treatment safety in patients with endometrial cancer.

This retrospective study included 208 endometrial cancer patients treated between January 2022 and January 2025. Patients were divided into a control group (n = 102), receiving conventional adjuvant therapy, and an observation group (n = 106), receiving molecular classification-based personalized regimens. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Secondary measures included objective response, treatment-related toxicity, treatment delivery factors, patient-reported outcomes, and next-generation sequencing of circulating tumor DNA (ctDNA). Multivariate Cox regression was used to explore molecular subtypes and clinicopathologic predictors of 5-year DFS.

In the observation group, immune therapy was exclusively administered, and treatment regimens significantly differed from the control group, which received chemoradiotherapy. The observation group showed significantly better DFS (HR = 0.52, 95% CI 0.30-0.89, P = 0.01) and OS (HR = 0.45, 95% CI 0.21-0.95, P = 0.03). Molecular subtype analysis indicated better prognosis for POLE-ultramutated tumors and poorer prognosis for p53-abnormal tumors. The observation group had fewer adverse events (grade ≥ 2: 38.7% vs. 63.7%, P = 0.001) and higher objective response rates (65.1% vs. 43.1%, P = 0.001).

Molecular classification-based adjuvant therapy improved survival, response rates, and ctDNA clearance with fewer toxicities. These findings support incorporating molecular classification into postoperative treatment to enhance outcomes in endometrial cancer.