ObjectiveTo determine the impact on overall survival (OS) of different modalities of adjuvant therapy for the treatment of stage III endometrial cancer (EC), by histology. MethodsStage 3 endometrioid (EAC), serous (SER), clear cell (CC), and carcinosarcoma (CS) patients who underwent primary surgical staging from 2000 to 2013 were identified in SEER-Medicare. Adjuvant therapy was defined by a 4-arm comparator grouping (none; RT only; CT only; combination RT), as well as by an 8-arm comparator grouping (none; RT only; CT only; concurrent CT-RT; concurrent CT-RT then CT; Serial CT-RT; serial RT-CT; sandwich). Modality of RT and CT were analyzed using Kaplan-Meier estimates, log rank tests, and multivariable cox modeling. ResultsOf 2870 cases identified (1798 EAC, 606 SER, 118 CC, 348 CS), 31.5% received no adjuvant therapy. The remainder received RT or CT alone, concurrent RT-CT, serial or sandwich modalities. OS differed by adjuvant therapy in adjusted and unadjusted models, when combining all histologies, and when stratifying by histology using both the 4-arm, and 8-arm comparator analyses (log rank p < .05, all). By histology, in adjusted analyses, sandwich modality had the greatest improvement in OS for endometrioid, but pairwise comparisons did not identify a superior chemotherapy-based regimen. For serous and clear cell, the greatest improvement in OS was seen with concurrent RT-CT, and for carcinosarcoma, CT alone. ConclusionsOS for advanced EC significantly differs by histology and mode of adjuvant therapy. Future studies should evaluate the efficacy of combination-based adjuvant therapy versus chemotherapy alone, by histologic subtype and molecular signature.