3729 - Molecular Classification-Guided Adjuvant Therapy and the Prognosis for Early-Stage Endometrial Carcinoma: Evidence from a Population-Based Cohort Study by Using IPTW Analysis
Presenter(s)
L. Xin1, K. Ren1, Z. Yan1, Y. Sheng1, Y. Wang1, Y. Zhang1, X. Hou1, H. Wu2, and F. Zhang1; 1Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 2Department of Pathology, State Key Laboratory of Complex Severe and Rare Disease, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Purpose/Objective(s): Molecular profiling has been shown to reduce recurrence in endometrial carcinoma (EC) while minimizing overtreatment and undertreatment. However, real-world evidence supporting its use in early-stage EC remains limited. This study compares outcomes for adjuvant therapy guided by molecular classification versus conventional clinicopathologic features in early-stage EC.
Materials/Methods: This study retrospectively enrolled FIGO 2009 stage I-II EC patients who underwent primary surgery followed by observation or adjuvant therapies between 2021 and 2025. Patients were assigned to molecular-guided therapy or standard therapy groups. Standard therapy followed ESGO 2021 guideline recommendations regardless of molecular profile; molecular-guided therapy included de-escalation or intensification.Inverse probability of treatment weighting (IPTW) analysis was used to balance the baselines between two groups. The Kaplan-Meier curves were used to illustrate the survival outcomes. Multivariate Cox regression was conducted to identify the independent prognostic risk factors.
Results: A total of 229 patients were enrolled and allocated to either molecular-guided therapy (n=63) or standard therapy (n=166). Median follow-up time was 31.13 months. Compared to standard therapy group, molecular-guided therapy group showed more aggressive histology types (33.3% vs. 18.1%, p=0.011), higher proportions of intermediate risk (39.7% vs. 20.5%, p=0.015), and p53abn (23.8% vs. 6.6%, p=0.021), and tended to receive radiotherapy (73.0% vs. 35.0%, p<0.001) or chemotherapy (19.0% vs. 11.4%, p<0.001). Overall, 15 patients received de-escalated therapy and 48 received intensified treatment. The 3-year overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates for the entire cohort were 100%, 90.9%, 94.9%, and 92.3%, respectively. Before IPTW, no significant differences in DFS, DMFS, or LRFS were observed between groups (all p>0.05). After IPTW, molecular classification-guided therapy significantly improved DFS (HR: 4.25, 95% CI: 1.34-13.46,p=0.01), DMFS (HR: 3.28, 95% CI: 1.00-10.75, p=0.0496), and LRFS (HR: 11.85, 95% CI: 1.49-94.15, p=0.0194). Multivariate Cox analysis before and after IPTW confirmed molecular-guided therapy as an independent predictor of better DFS, DMFS, and LRFS. In the molecular-guided group, recurrences often extended beyond the pelvis (n=5); in the standard group, recurrences were pelvic (n=3) or extra-pelvic (n=10). Both regimens were well tolerated; only one grade 3 urinary event (urinary frequency) was observed in the standard therapy group.
Conclusion: Molecular classification-guided therapy significantly improved prognosis in early-stage EC patients by reducing both undertreatment and overtreatment. It demonstrated independent prognostic value, supporting its integration into routine management of early-stage EC.