Impact of the new molecular classification of endometrial cancer: A French cohort study

Objective: To evaluate the potential impact of the latest ESGO guidelines for endometrial cancer with molecular classification on the management strategy in a French cohort.

Methods: All patients treated between January 1st, 2014 and December 31, 2020 for an endometrial cancer at the Centre Hospitalier Intercommunal de Créteil (CHIC, FRANCE) were selected from our prospectively maintained database. All postoperative samples were reviewed to confirm histological subtype, myometrial infiltration, cytonuclear grade and presence of lymphovascular emboli. Analysis of p53, MLH1, MSH2, MSH6, PMS2 genes was performed by immunohistochemistry first then a systematic POLE sequencing was performed to identify gene mutation. The impact of the latest ESGO 2020 guidelines was assessed regarding adjuvant therapy, surgical strategy, and survival.

Results: Eighty patients were analyzed, including 70% NSMP (n = 56), 13.75% MSI (n = 11), 10% p53 mutated (n = 8) and 6.25% POLEmut (n = 5). A total of 21 patients (26.3%) were reclassified using the latest ESGO classification. Patients classified at low risk or with advanced / metastatic disease were not reclassified using molecular analysis. Molecular analysis and the latest ESGO classification had the most important impact on patients initially classified at intermediate - high risk that were reclassified in intermediate (10/23) and in low (4/23) risk. Nine patients (11.3%) were overtreated according to the 2020 ESGO classification: six patients in the low - risk group (4 received vaginal brachytherapy and 2 external radiotherapy) and three in the intermediate risk group (3 received external irradiation and 1 received chemotherapy). None of the patients in our cohort would have been undertreated using the 2020 ESGO classification. Patients within the p53 mutated group were the most likely to experience recurrence (37.5%, 3/8) and none of the patients POLE mutated recurred.

Conclusion: Around one in 4 patients were reclassified in a more accurate prognostic group using molecular diagnosis and the latest ESGO guidelines which could decrease the use of adjuvant therapies to spare morbidity.