382 Molecular Classification of Endometrial Carcinoma Substantially Changing Risk-Assessment: Results from a European Multicentre Initiative

Introduction/Background* Endometrial carcinoma patient care was based on histopathologic examination for many years. However, conventional pathologic features are known to suffer from high inter-observer variability and may be irreproducible in many cases. TCGA-derived molecular classification was shown to provide clinically meaningful data and was recently introduced to ESGO/ESTRO/ESP endometrial carcinoma consensus guidelines. It was the aim of this study to quantify alterations in risk-assessment if molecular classification is added to conventional prognosticators. Methodology Consecutive primary endometrial carcinoma patients diagnosed in 2016 were identified in participating centres. Original risk classification (‘ORC16’, ESGO/ESMO guidelines 2016) was compared to current molecular-based risk assessment (‘MBR21’, ESGO/ESMO guidelines 2021). Clinical and histopathological data were collected and tumor specimens were retrospectively submitted to PMS2, MSH6 and p53 immunohistochemistry and POLE mutation testing. Result(s)* 226 patients were identified across five major European gynecologic oncology centres. Complete molecular and clinical data were available from 198 cases with a median follow-up time of 52.1 months. Median age was 64.9 years (30.9-90.9), 165 cases (83,3%) were endometrioid histotype. Grade distribution included 85(42.9%) G1, 63(31.8%) G2, and 46(23.3%) G3 tumors. 98(49.5%) patients had stage IA disease, with the remaining stage IB (n=51;25.8%), stage II (n=16;8.0%), and stage III/IV (n=33;16.7%). Molecular classification yielded 43(21.7%) MMR-D, 18(9.1%) POLE, 43(21.7%) p53abn, and 94(47.5%) p53wt tumors. If ORC16 was compared to MBR21, risk was found to be higher in 15(7.6%) cases, whereas 27(13.6%) cases were assigned to a lower risk group. No survival events were observed in the 9 patients where risk was changed from high-intermediate or high to low-risk. Conclusion* We were able to demonstrate clinically relevant alterations of endometrial carcinoma risk assessment in a significant number of patients after adding TCGA-derived molecular data to conventional risk classification. Potential molecular-guided changes in patient management may help to avoid over- and undertreatment and will ultimately give rise to precision medicine strategies in endometrial carcinoma patient care.