The Correlation Between Tumor Gross Type and Pathological Response Rate of Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma

Abstract Background Neoadjuvant chemoimmunotherapy has emerged as a promising strategy for locally advanced esophageal squamous cell carcinoma (ESCC), yet the patients who will benefit from such treatment have not been fully defined. We aimed to systematically evaluate the association of clinicopathological features with efficacy of neoadjuvant chemoimmunotherapy. Methods This single-center study retrospectively enrolled 409 ESCC patients who underwent neoadjuvant chemoimmunotherapy followed by surgery (January 2020–July 2025). Pathological responses were assessed, and the associations with clinicopathological features were analyzed using univariate and multivariate logistic regression. Results The pathological complete response (pCR) rate was 22.2%, and the major pathological response (MPR) rate was 39.4%. Female patients were associated with higher pCR (34.3% vs. 19.9%, p = 0.015). Tumor location significantly influenced MPR, with proximal tumors achieving the highest rate (47.9%) and distal tumors the lowest (30.2%) ( p = 0.013). The constrictive gross type showed markedly lower pCR (3.5% vs. 23.7%, p = 0.022) and MPR (20.7% vs. 40.8%, p = 0.053) compared with other types. Carboplatin was associated with significantly higher MPR (44.7%) compared to cisplatin (21.2%) or nedaplatin (25.7%) ( p < 0.001). Multivariate analysis identified constrictive type and carboplatin as independent predictors of both pCR (OR = 0.101, p = 0.027; OR = 5.514, p = 0.024, respectively) and MPR (OR = 0.349, p = 0.032; OR = 2.971, p = 0.018, respectively). Distal tumor location independently predicted lower MPR (OR = 0.474, p = 0.019). Conclusions Tumor location, tumor gross type (particularly constrictive type), and platinum agents selection might independently influence the pathological response to neoadjuvant chemoimmunotherapy in locally advanced ESCC. These findings may inform patient stratification and treatment optimization in clinical practice.