Comparison of perioperative chemotherapy and neoadjuvant chemoradiotherapy (CRT) in locally advanced resectable distal esophageal/esophagogastric junction (EGJ) adenocarcinomas

OBJECTIVE: To compare the real-world outcomes of perioperative chemotherapy (ChT) and neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced resectable distal esophageal and esophagogastric junction (EGJ) adenocarcinomas, with respect to pathological response, overall survival (OS), and recurrence-free survival (RFS). MATERIALS AND METHODS: This retrospective cohort study included 119 patients treated between 2016 and 2025 at a tertiary oncology center. Patients received either perioperative ChT (n = 68) or neoadjuvant CRT (n = 51) followed by curative-intent surgery. Baseline clinicopathological characteristics were comparable between groups. Survival outcomes were analyzed using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards regression models were constructed to identify independent prognostic factors for OS. RESULTS: A total of 119 patients were included, with comparable baseline characteristics between groups. Neoadjuvant CRT achieved higher pathological complete response and downstaging rates (p = 0.034 and p = 0.005), but no significant difference in overall survival (OS) (p = 0.944) or recurrence-free survival (RFS) (p = 0.449) was observed. In subgroup analyses, neoadjuvant CRT showed a trend toward improved OS in EGJ stage II (p = 0.078) and a significant RFS benefit in distal stage II (p = 0.014), whereas perioperative ChT demonstrated a significant OS advantage in EGJ stage III (p = 0.020). Treatment modality was not an independent predictor of OS, while nodal involvement was the strongest adverse prognostic factor. CONCLUSION: Neoadjuvant CRT improved pathological response but did not provide a survival advantage over perioperative chemotherapy in the overall population. Subgroup analyses suggested stage- and location-dependent differences, although these findings are hypothesis-generating. Both strategies showed comparable survival outcomes, supporting individualized treatment selection. Larger prospective studies are needed for validation.