Background: The comparative effectiveness of trimodal therapy versus definitive chemoradiation for older adults with locally advanced esophageal cancer is uncertain. Only two randomized trials have considered this comparison, and older adults and patients with adenocarcinomas were underrepresented. Older adults have greater frailty and may not benefit from adding surgery to chemoradiation. Methods: A cohort of adults 66-79 years of age diagnosed with incident locally advanced esophageal cancer between 2004 and 2017 was identified using the Surveillance Epidemiology and End Results-Medicare database. We used observational data to emulate a hypothetical trial comparing trimodal therapy and definitive chemoradiation. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home. Results: The study population included 1,240 individuals with adenocarcinomas and 661 with squamous cell carcinomas. Amongst older adults diagnosed with adenocarcinomas, the five-year risk of mortality was 73.4% (95% CI: 69.1–77.4) in the trimodal therapy group and 83.8% (95% CI: 78.6–87.2) in the definitive chemoradiation group (RR= 0.88, 95% CI: 0.82–0.95). Amongst older adults diagnosed with squamous cell carcinomas, the five-year risk of mortality was 62.6% (95% CI: 50.9–73.5) in the trimodal therapy group and 72.3% (95% CI: 67.6–76.3) in the definitive chemoradiation group (RR= 0.87, 95% CI: 0.70–1.01). Results for all outcomes are presented in the Table. Conclusions: Trimodal therapy was associated with lower mortality than definitive chemoradiation. The benefits were smaller than suggested by prior observational studies. These findings can be used with clinical expertise and patient preferences to enhance shared decision-making.

Abbreviations: dCR, definitive chemoradiation; RR, risk ratio*Healthy days at home was measured in days (not risk)