Association of modality of adjuvant radiation and chemotherapy with survival outcomes for stage IIIA/IIIB and IIIC endometrial cancers

Abstract

<h3>Objectives:</h3> Although adjuvant therapy with radiation (RT) or chemotherapy (CT) is recommended for advanced endometrial cancer, prior studies have not defined which modality of adjuvant therapy is most effective for advanced node-negative versus node-positive disease. This study investigates the impact of various adjuvant therapies on overall survival (OS) for patients with Stage IIIA/IIIB and IIIC endometrioid endometrial cancer (EC). <h3>Methods:</h3> The SEER-Medicare database was used to identify patients with stage III endometrioid EC who underwent primary hysterectomy from 2005-2015, with Medicare claims data through 2016. Cases of stage IIIA/B and IIIC disease were analyzed separately. Demographic data, adjuvant therapy modality and sequence, and pathologic findings were collected. ‘Simplified Treatment Classification' was defined by collapsing all modalities of combined CT/RT. ‘Treatment Sequence Specified' maintained separate groups of sequence specifications. Descriptive analyses followed by Kaplan-Meier curves, Cox multivariable modeling, and pairwise comparisons with Bonferonni corrections were used to assess 5-year OS by treatment modality. <h3>Results:</h3> 2,045 patients were identified (n=1046 IIIA/B; n=977 IIIC). RT alone (33%) followed by CT alone (18%) were most commonly used in stage IIIA/B (33%); whereas CT alone (29%) and combination CT-RT (26%) were most common for stage IIIC. Treatment with RT alone decreased significantly for both groups after 2008 (42.32% to 20.25% for IIIA/B, 34.31% to 10.56% for IIIC, p<0.0001). The receipt of any adjuvant treatment improved OS compared to no treatment in both stage IIIA/B and IIIC in both unadjusted and adjusted comparisons (Table 1). For both IIIA/B and IIIC, pairwise comparison of concurrent CT/RT was not significantly improved over CT alone (>0.05 all). However, both CT alone and concurrent CT/RT were associated with improved survival compared to use of RT alone for IIIA/IIIB (CT HR 0.60, 95% CI 0.45, 0.81, p<.0001; concurrent CT/RT HR 0.60, 95% CI 0.40, 0.90, p=0.008). For IIIC, concurrent CT/RT was associated with improved survival compared to RT alone (HR 0.63, 95% CI 0.44, 0.92, p=.01), however chemotherapy alone was not (p=0.07). When collapsed to use of any type of combination CT-RT regardless of sequence, there was no significant difference of combination CT-RT compared to CT alone for either IIIA/IIIB or IIIC patients (pairwise comparisons all p>0.05). <h3>Conclusions:</h3> In stage IIIA/B, both concurrent CT/RT and CT alone conferred improved survival compared to RT alone. In contrast for IIIC, concurrent CT/RT conferred improved survival over RT alone, whereas CT alone did not. For both IIIA/IIIB and IIIC, pairwise comparisons did not show improvement of using combination CT-RT over CT alone. There did not appear to be a clear difference in pattern of efficacy of various CT or RT regimens between node positive (IIIC) versus node negative (IIIA/B) advanced stage endometrioid adenocarcinomas.