Extracapsular Nodal Extension as a Key Prognostic Factor in FIGO IIIC Endometrial Carcinoma: A Clinic–Pathologic and Molecular Analysis

Background: Assessment of lymph node involvement was incorporated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system as a critical determinant of patient management and prognostication. This study aims to validate the prognostic significance of metastatic lymph node characteristics and their correlation with molecular classification. Methods: We conducted a retrospective analysis of 131 patients with stage IIIC endometrial carcinoma who underwent surgical intervention at the Tianjin Medical University Cancer Institute and Hospital from 2010 to 2025. The patients were stratified based on various characteristics of metastatic lymph nodes. Progression-free survival (PFS) was estimated using Kaplan–Meier curves, and group comparisons were performed using the log-rank test. Univariate Cox proportional hazards regression was conducted to identify independent prognostic factors for PFS. Results: In accordance with the 2023 FIGO staging system, within the stage IIIC cohort, patients with concurrent pelvic and para-aortic lymph node metastases and those in the stage IIIC1 cohort with macrometastasis demonstrated decreased PFS (HR = 2.748; 95% CI = 1.227–6.151; p = 0.011, and HR = 4.039; 95% CI = 1.232–13.240; p = 0.021, respectively). Furthermore, patients with lymph nodes showing extracapsular extension had significantly reduced PFS in the stage IIIC, stage IIIC1, and stage IIIC1ii cohorts (HR = 10.12; 95% CI = 2.38–42.99; p < 0.001; HR = 3.58; 95% CI = 1.242–10.31; p = 0.011; and HR = 2.32; 95% CI = 0.83–6.71; p = 0.037, respectively). The number of involved lymph nodes, the largest diameter of metastatic foci in lymph nodes, and the presence or absence of extracapsular extension of metastatic lymph nodes were significantly different among the NSMP, MMRd, and p53abn molecular classifications (p = 0.033, p < 0.001, and p = 0.002, respectively). Patients with extracapsular extension of metastatic lymph nodes had worse PFS than those without in the MMRd group (p = 0.018). Conclusions: Extracapsular extension (ECE) of metastatic lymph nodes is the strongest predictor of worse progression-free survival in stage IIIC endometrial carcinoma, especially in the IIIC1 and MMRd subgroups, supporting its value for risk stratification and prognostic assessment.