1025 - Clinicopathologic and Molecular Heterogeneity of Aggressive Endometrial Carcinoma in the 2023 FIGO Staging System: A Dual-Cohort Retrospective and Prospective Analysis
Presenter(s)
K. Ren1, Z. Yan2, W. Wang3, L. Xin4, F. Zhang5, K. Hu6, and X. Hou3; 1Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of medical Sciences & Peking Union Medical College, Beijing 100730, China, China, 2Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academic of Medical Sciences and Peking Union Medical College,, Beijing, China, 3Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of medical Sciences & Peking Union Medical College, Beijing, China, 4eking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Beijing, China, 5Department of Radiation Oncology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China, 6Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Purpose/Objective(s):
The 2023 revised FIGO staging system categorizes high-grade endometrioid carcinoma (ECs) and non-endometrioid carcinoma as aggressive histologies. However, the clinicopathologic and molecular characteristics of these subtypes remain incompletely understood. This study aimed to elucidate the characteristics of aggressive ECs to explore their underlying biological heterogeneity and clinical implications.Materials/Methods:
This cohort study included retrospectively collected EC cases from 2000 to 2020 and a prospective cohort from 2021 to 2024 at Peking Union Medical College Hospital. Patients who underwent staging surgery were reclassified according to the 2023 FIGO staging criteria and those staged as FIGO IC or IIC were included in the analysis. Overall survival and recurrence-free survival (RFS) were assessed using Kaplan-Meier curves, and Cox proportional hazards models were employed for multivariate analysis. DeconstructSigs was utilized to show the correlations between mutational signatures and clinicopathologic features.Results:
A total of 306 patients were included, comprising 4 FIGO IC and 302 FIGO IIC cases. Sankey diagrams illustrated the transition from the 2009 to the 2023 FIGO staging system, patient selection criteria, and adjuvant treatment strategies for molecular subtypes. Lymphovascular space invasion (LVSI) (hazard ratio [HR] = 3.36; 95% confidence interval [CI], 1.025–11.002; p = 0.023) and estrogen receptor(ER) negativity (HR = 4.39; 95% CI, 1.096–17.541; p = 0.037) were identified as independent predictors of worse RFS in aggressive histologies. Molecular classification revealed that p53abn was the most prevalent subtype (33.8%), followed by MMRd (28.2%), NSMP (16.9%), and POLEmut (21.2%). p53abn exhibited the poorest prognosis, with a 1-year RFS of 86.1%. MMRd demonstrated aggressive clinicopathologic features, including deeper myometrial invasion(MMI) (60%, p=0.093) and higher LVSI positivity (65%, p = 0.002). POLEmut demonstrated the most favorable RFS and exhibited a higher co-occurrence rate of BRCA1/2 mutations (33.3% for BRCA1 and 80% for BRCA2; p < 0.05). These tumors were also characterized by less aggressive features, such as exclusive endometrioid histology and limited MMI. Regarding adjuvant therapy, POLE-mutated tumors exhibited the highest proportion of postoperative radiotherapy omission, reaching up to 46.7%, while p53abn tumors were most frequently treated with pelvic radiotherapy (66.7%, p = 0.032).Conclusion:
The adoption of the 2023 staging system has led to a significant shift in early-stage EC, particularly for FIGO IC and IIC cases. Our findings highlight that aggressive histologies are not homogeneous, with ER negativity and LVSI positivity correlating with poorer outcomes. Molecular profiling revealed distinct distributions of molecular subtypes within aggressive histologies, providing a foundation for refined risk stratification and personalized adjuvant treatment strategies.