Prognostic value of pathological response and nodal status after neoadjuvant chemoimmunotherapy for esophageal squamous cell carcinoma

To identify prognostic factors for pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS) in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoimmunotherapy (nCIT) followed by esophagectomy. We retrospectively analyzed 441 consecutive patients with locally advanced ESCC who received nCIT followed by R0 esophagectomy at a single high-volume center (2019–2023). Multivariable logistic regression and Cox proportional hazards models were used to identify factors associated with pCR, DFS, and OS. Variables included age, sex, clinical stage, tumor location, chemotherapy type (paclitaxel vs. nab-paclitaxel), PD-1 inhibitor type, number of neoadjuvant cycles, ypT, ypN, tumor regression grade (TRG), number of lymph nodes dissected, and adjuvant therapy. The overall pCR rate was 19.0% (84/441). On multivariable analysis, female sex ( P = 0.005), PD-1 inhibitor pembrolizumab ( P = 0.003) and tislelizumab ( P = 0.003) were independently associated with higher pCR. With a median follow-up of 25 months, independent factors for improved DFS and OS included lower ypN stage, higher number of lymph nodes dissected, and receipt of adjuvant therapy (all P < 0.05). Notably, TRG was independently associated with both DFS and OS in the multivariable model (all P < 0.05). PD-1 inhibitor type and chemotherapy regime was not associated with DFS or OS (all P > 0.05). In this real-world cohort, pCR varied by PD-1 inhibitor type, but survival outcomes were primarily determined by nodal status and TRG, rather than ypT status. Extensive lymph node dissection and adjuvant therapy were independently associated with improved survival. These findings underscore the importance of surgical quality, postoperative systemic treatment, and response-based risk stratification in the nCIT era.