Is induction therapy optimal for all patients with locally advanced distal esophagus adenocarcinoma?-The impact of age and co-morbidities on treatment and outcomes.

Background: The benefits to induction chemoradiation for esophageal adenocarcinoma patients are established, but optimal management for patients who cannot tolerate trimodality therapy is not clear. This study tested the hypothesis that subsets of high-risk patients have better survival with primary surgery compared to induction therapy. Methods: The survival benefit of induction chemoradiation versus primary surgery was evaluated with the Kaplan-Meier method, log-rank test, and Cox proportional hazards modeling for patients with locally advanced (cT3N0M0, cT1-3N+M0) mid-distal esophageal adenocarcinoma in the National Cancer Database from 2006-2019, including subsets of patients over the age of 80 years and those with a Charlson-Deyo comorbidity index ≥2. Results: Most of 13,985 esophagectomy patients received induction chemoradiation (n=12,999, 92.3%), with 7.0% (n=986) having primary surgery. Primary surgery use was less common in years 2010-2019 compared to earlier (5.0% versus 15.4%, P<0.001). Increasing age and Charlson-Deyo comorbidity score ≥2 were associated with less likely use of induction chemoradiation. Induction therapy was associated with better survival compared to primary surgery in univariate (5-year survival 40.1% Conclusions: Esophageal adenocarcinoma patients have improved survival when treated with induction chemoradiation compared to primary surgery irrespective of age or comorbidity status. A strategy utilizing induction therapy is reasonable to consider in all patients considered acceptable candidates for all three treatment modalities.