Purpose: Risk stratification to select appropriate candidates for adjuvant therapy is required for esophageal cancer patients based on adjuvant therapy advancement including immunotherapy. The current study aims to develop a novel staging system using pathological stage (pStage) and response to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC). Methods: ESCC patients who received NAC and underwent transthoracic esophagectomy at two Japanese high-volume esophageal centers were retrospectively reviewed. The prognostic value of NAC response was evaluated within the same pStage, and a novel risk stratification to predict cancer-specific survival (CSS) was developed. Results: The HR (95% CI) of pathological responders in pStage 0–I, II, III, and IV was 0.29 (0.07–1.17), 0.37 (0.12–1.10), 0.37 (0.15–0.92), and 0.24 (0.06–0.98), respectively. Responders in pStage 0–II were classified to be in the same class and those in pStage III/IV in another group, because the 5-year CSS (5y-CSS) rate of responders in pStage 0–I, II, III, and IV was 94%, 92%, 76%, and 71%, respectively. Combining nonresponders in pStage 0–II as the same group, all patients were subdivided into five groups. Intriguingly, the 5y-CSS in pStage III–IV responders was 75%, almost identical to that of nonresponders in pStage 0–II (78%). Conclusions: The histological response influenced the long-term outcomes of patients who underwent esophagectomy after NAC, even within groups stratified by pathologic stage. The current risk stratification system will contribute to selecting appropriate candidates for adjuvant therapy.
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