Radiation therapy does not improve survival in patients who are upstaged after esophagectomy for clinical early-stage esophageal adenocarcinoma

Objective: Radiation after esophagectomy may cause conduit dysfunction with unclear oncologic benefits. We hypothesized that adjuvant chemoradiation does not improve survival over chemotherapy alone for patients with pathologic upstaging after primary surgery for cT1-2N0M0 esophageal adenocarcinoma. Methods: The impact of adjuvant therapy after primary surgery for cT1-2N0M0 esophageal adenocarcinoma upstaged to pT3-4 or pN+ in the National Cancer Database (2004-2019) was evaluated with logistic regression, Kaplan-Meier analysis, and Cox modeling. Results: A total of 574 patients met inclusion criteria, 300 (52.3%) who received adjuvant therapy (chemotherapy alone in 117 [39.0%], radiation alone in 15 [5.0%], chemoradiation in 168 [56.0%]) and 274 (47.7%) who did not. Adjuvant therapy was associated with improved 5-year survival (46.8% vs 32.7%, P <.001). In multivariate analysis controlling for age, year of diagnosis, Charlson Co- morbidity Index, pT, pN, and positive margins, adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.62, 95% CI, 0.46-0.84, P = .002); radiation use did not have a statistically significant association with survival (hazard ratio, 1.19, 95% CI, 0.86-1.63, P = .29). Among patients who received chemotherapy, independent predictors of also receiving radiotherapy included pathological T-upstaging (odds ratio, 2.01, 95% CI, 1.04-3.88, P = .037) and distance from facility less than 50 miles (odds ratio, 2.13, 95% CI, 1.05-4.33, P = .037). In univariate analysis of patients who received adjuvant therapy, chemotherapy alone was associated with significantly better 5-year survival compared with chemoradiation (54.2% vs 41.6%, P = .004). Landmark analyses at 3 and 6 months were consistent with the primary analysis. Conclusions: Using radiation with chemotherapy as adjuvant therapy for patients upstaged after esophagectomy for cT1-2N0 esophageal adenocarcinoma is not associated with improved survival and should be considered only in select situations based on careful clinical evaluation. (JTCVS Open 2025;23:290-308)