Association of Chemoradiation, Trimodality Therapy, or Salvage Resection with Survival in Stage II-III Esophageal Squamous Cell Carcinoma.

Objective: Esophageal squamous cell carcinoma(ESCC) remains highly lethal and often under-treated. 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.

Methods: This retrospective analysis of the 2004-2021 National Cancer Database identified all clinically-staged II-III ESCC patients≥18years. Patients undergoing chemotherapy and ≥41.4 Grays of radiation across 28 fractions, followed by esophagectomy <90 days were considered the trimodality cohort, while those undergoing resection ≥90 days were classified as salvage. Patients receiving definitive chemoradiation were categorized as definitive CRT.

Results: Of 3,786 patients, 912 (24%) underwent trimodality therapy, 173 (5%) chemoradiation followed by salvage resection, and 2,701 (71%) definitive CRT. Following risk-adjustment and relative to definitive CRT, trimodality was linked with greater survival at 1 (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 year: HR 0.54, CI 0.40-0.73). Upon RMST analysis, trimodality demonstrated a 9.17 month (CI 6.40-11.94) incremental increase in overall survival time over 5 years, while salvage was linked with a 10.03 month (CI 4.04-16.03) increase in survival time, compared to definitive CRT.

Conclusions: Surgical resection following chemoradiation confers survival benefit and should be considered a mainstay in the management of locoregionally-advanced ESCC. Yet, with comparable outcomes across trimodality and salvage approaches, organ preservation may be appropriate, for select patients.