Association of chemoradiation, trimodality therapy, or salvage resection with survival in stage II-III esophageal squamous cell carcinoma.

Abstract

Esophageal squamous cell carcinoma remains highly lethal and often undertreated. With conflicting evidence regarding the additional benefit of surgical resection to chemoradiation, many patients with locoregionally advanced disease may receive chemoradiation and then undergo evaluation for progression before esophagectomy. We hypothesized that trimodality therapy or salvage resection would be linked with superior overall survival, relative to definitive chemoradiation. This retrospective analysis of the 2004-2021 National Cancer Database identified all patients aged 18 years or more with clinically staged II-III esophageal squamous cell carcinoma. Patients undergoing chemotherapy with 41.4 Gy or more of radiation across 28 fractions, followed by esophagectomy at less than 90 days, were considered the trimodality cohort, and those undergoing resection at 90 days or more were classified as salvage. Patients receiving definitive chemoradiation were categorized as definitive chemoradiotherapy. Of 3786 patients, 912 (24%) underwent trimodality therapy, 173 (5%) received chemoradiation followed by salvage resection, and 2701 (71%) received definitive chemoradiotherapy. After risk adjustment and relative to definitive chemoradiotherapy, trimodality was linked with greater survival at 1 year (hazard ratio [HR], 0.45, CI, 0.34-0.59) and 5 years (HR, 0.57, CI, 0.49-0.66), as was salvage (1 year: HR, 0.38, CI, 0.22-0.69; 5 years: HR, 0.54, CI, 0.40-0.73). On restricted mean survival time analysis, trimodality demonstrated a 9.17-month (CI, 6.40-11.94) incremental increase in overall survival time over 5 years, whereas salvage was linked with a 10.03-month (CI, 4.04-16.03) increase in survival time compared with definitive chemoradiotherapy. Surgical resection after chemoradiation confers a survival benefit and should be considered a mainstay in the management of locoregionally advanced esophageal squamous cell carcinoma. Yet, with comparable outcomes across trimodality and salvage approaches, organ preservation may be appropriate for select patients.