Does Sequencing of Adjuvant Therapy Influence Outcome for Stage IIIC Endometrial Carcinoma? A Multi-institutional Analysis

Abstract

In GOG-258, patients who received upfront chemoradiotherapy had more distant relapses compared to those treated with systemic chemotherapy alone, although vaginal and nodal recurrence rates were lower with the addition of adjuvant radiotherapy (RT). Given the importance of both systemic and local therapies, this study evaluates clinical outcomes by the sequence and type of adjuvant therapy for patients with stage IIIC endometrial cancer (EC). In a multi-institutional retrospective cohort study, clinical and treatment data from 12 academic centers were collected for patients with stage IIIC EC treated with curative intent. All patients had surgical staging and received chemotherapy and radiation. Adjuvant treatment (AT) regimens were classified as: adjuvant chemotherapy followed by sequential radiation (ACTRT), concurrent chemoradiation followed by chemotherapy (CCTRT), systemic chemotherapy before and after RT (Sandwich), adjuvant RT followed by chemotherapy (ARTCT) or chemotherapy concurrent with vaginal cuff brachytherapy alone (CCTBT). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by Kaplan-Meier method and covariates were compared by log-rank test. Chi-square tests were used to compare categorical variables. A total of 670 eligible patients were included (Table) with a median follow-up of 44.1 months. The estimated 5-year OS and RFS rates were 71.5% and 65.5%, respectively. On univariate analysis (UVA) for OS, older age, non-white race, non-endometrioid histology, grade 3 tumor, 2 or more positive nodes, adnexal involvement, cervical involvement, stage IIIC2 vs. IIIC1, and in-field recurrence were associated with worse OS (all p<0.02). On UVA for RFS, older age, non-endometrioid histology, grade 3 tumor, lymphovascular invasion, adnexal involvement, cervical involvement and stage IIIC2 were associated with recurrence. The sequence and type of adjuvant therapy was not correlated with OS or RFS (p = 0.08 and 0.8, respectively). The most common pattern of recurrence was distant metastasis only (66%). Site of first recurrence was significantly different by adjuvant treatment regimen (p = 0.02): ACTRT, CCTRT and Sandwich had a higher proportion of distant metastasis whereas ARTCT and CCTBT had more para-aortic nodal recurrences. Pelvic control was highest for ACTRT. The sequence and type of adjuvant therapy did not impact OS or RFS rates, which were comparable to those of the prospective GOG 258 and PORTEC-3 studies. Adjuvant radiotherapy resulted in excellent pelvic control. Most recurrences were distant despite upfront systemic chemotherapy given in most patients, highlighting the need for novel regimens.Abstract 102; TableFactornAge, Median62Race Caucasian African-American Other480 83 47Stage IIIC1 IIIC2430 240Histology Endometrioid Non-endometrioid441 229Grade 1-2 3320 346RT EBRT BT Both176 94 400Adjuvant therapy ACTRT CCTRT Sandwich ARTCT CCTBT290 112 165 26 77 Open table in a new tab