Molecular subtype stratified outcomes according to adjuvant therapy in endometrial cancer

Objectives. Recent data support the predictive implications of molecular subtype assignment in endometrial cancer (EC). Our objective was to retrospectively assess clinical outcomes according to adjuvant treatment re-ceived within EC molecular subtypes. Methods. Clinical outcomes (disease-specific and progression-free survival DSS/PFS) of EC patients from a sin-gle institution and population-based cohorts that had undergone molecular classification were assessed with re-spect to adjuvant therapy received and 2016 ESMO risk group.Results. 2472 ECs were assessed; 184 (7.4%) POLEmut, 638 (25.8%) MMRd, 1223 (49.5%) NSMP and 427 (17.3%) p53abn. N = 774 (34.6%) of the cohort were ESMO 2016 high risk and 109 (4.8%) were advanced or me-tastatic. In patients with MMRd EC, assessed across and within stage, there was no observed benefit in DSS or PFS with the addition of chemotherapy +/- radiation compared to radiation alone in ESMO high risk (p = 0.694) or ESMO high, advanced, metastatic risk groups combined (p = 0.852). In patients with p53abn EC, adjuvant chemotherapy given with radiation was associated with significantly longer DSS compared to radiation alone in ESMO high risk (p = 0.007) and ESMO high, advanced and metastatic risk groups combined (p = 0.015), even when restricted to stage I disease (p < 0.001) and when compared in serous vs. non-serous histotypes (p = 0.009).Conclusions. Adjuvant chemotherapy is associated with more favorable outcomes for patients with p53abn EC, including stage I disease and non-serous histotypes, but does not appear to add benefit within MMRd ECs for any stage of disease, consistent with PORTEC-3 molecular subanalysis. Prospective trials, assessing treatment efficacy within molecular subtype are needed, however these 'real-world' data should be considered when discussing adjuvant treatment with patients.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

The clinical outcomes of endometrial cancer (EC) patients vary according to different molecular subtypes and adjuvant treatments. For MMRd EC patients, there is no significant benefit in DSS or PFS with the addition of chemotherapy +/- radiation compared to radiation alone. However, for p53abn EC patients, adjuvant chemotherapy given with radiation is associated with significantly longer DSS, even in stage I disease and non-serous histotypes.