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Background  This study investigated the prognostic impact of (neo‐)adjuvant radiation therapies in early stage esophageal cancer.    Methods  A retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database was conducted from 2004 to 2016. Patients with pathologically staged T1‐4N0M0 esophageal cancer were divided into two treatment groups: (i) neoadjuvant radiotherapy followed by surgery; and (ii) upfront esophagectomy followed by adjuvant radiotherapy. Propensity scored match and Cox proportional hazards model were used to identify covariates associated with overall survival and cancer‐specific survival.    Results  There were 821 patients selected, of whom 588 (71.6%) received neoadjuvant radiotherapy and 233 (28.4%) received adjuvant radiotherapy. For the entire cohort, neoadjuvant radiotherapy was associated with a significantly benefit in five‐year survival outcomes compared with adjuvant radiotherapy ( P  < 0.01). After matching, the survival outcomes were still better for neoadjuvant radiotherapy than that of adjuvant treatment. Stratifying based on pathologic tumor status, neoadjuvant radiation was associated with improved CSS (five‐year survival 73.7% vs. 42.1%;  P  = 0.014) for localized (pT3‐4N0) disease. The Cox multivariate regression analysis revealed that the addition of neoadjuvant radiation for pT3‐4N0 diseases with tumor length ≥ 5 cm and squamous cell carcinoma, was a powerful prognostic factor for improved cancer‐specific survival ( P  < 0.01).    Conclusions  Compared with adjuvant radiotherapy, the addition of neoadjuvant radiation for pT3‐4N0 diseases has been associated with improved cancer‐specific survival in high‐risk patients. Studies on preoperative neoadjuvant therapies would be plausible in high‐risk esophageal cancer patients.

Role of radiation therapy in node‐negative esophageal cancer: A propensity‐matched analysis