Definitive Chemoradiotherapy vs. Trimodal Therapy for Locally Advanced Esophageal or Junctional Adenocarcinoma

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<h3>Purpose/Objective(s)</h3> Randomized trials have not found trimodal therapy to improve overall survival (OS) compared to definitive chemoradiotherapy for esophageal cancer, but these studies were small and included few adenocarcinoma cases. We sought to compare OS between trimodal therapy and definitive chemoradiotherapy for locally advanced adenocarcinoma of the esophagus and gastroesophageal junction. <h3>Materials/Methods</h3> Patients with locally advanced esophageal or junctional adenocarcinoma undergoing either definitive trimodal therapy or chemoradiotherapy between 2004 and 2018 were retrospectively identified in the provincial cancer registry. The primary analysis was based on intention to treat as determined by chart review (trimodal therapy or definitive chemoradiotherapy). A per-protocol analysis was also completed, wherein patients not undergoing surgery were excluded from the trimodal group, and patients not receiving radiotherapy to at least 41.4 Gy in 23 fractions were excluded from both groups. Kaplan-Meier curves and the Cox proportional hazard model with covariates of age, sex, stage, chemotherapy regimen, and EQD2 (α/β = 4.0) were used to compare OS. <h3>Results</h3> A total of 484 patients were eligible for analysis with a median follow-up of 39.1 months. Median age was 62 with a preponderance of males (87%). Most patients with a clinical AJCC 8th edition stage were stage III (71%), followed by stage IV (21%). The most common dose fractionation schedule was 41.4 Gy in 23 fractions (74%), and the most common chemotherapy regimen was carboplatin/paclitaxel (78%). At the outset, 428 were planned for trimodal therapy and 56 were planned for definitive chemoradiotherapy. There were 67 patients (16%) planned for trimodal therapy who did not undergo surgery, and 15 patients (3%) did not receive at least 41.4 Gy in 23 fractions. By intention to treat, median survival was 24.1 months for trimodal therapy and 21.9 months for definitive chemoradiotherapy. Per protocol, median survival was 30.9 months for trimodal therapy compared to 28.2 months for definitive chemoradiotherapy. No difference in OS was detected either by intention to treat (Cox HR: 0.81; 95% CI: 0.52-1.26; p=0.4) or per protocol (Cox HR: 0.72; 95% CI: 0.42-1.24; p=0.2). <h3>Conclusion</h3> No difference in OS was detected between trimodal therapy and definitive chemoradiotherapy. Our HR was more favorable for definitive chemoradiotherapy than previous retrospective studies on esophageal adenocarcinoma, possibly reflecting the use of treatment intent to account for trimodal patients who fail to undergo surgery. These findings suggest that definitive chemoradiotherapy may be an alternative to trimodal therapy for selected patients after weighing any potential of trimodal therapy prolonging survival against operative morbidity, operative mortality risk, and cost, but further studies including randomized controlled trials are required.