Comparative Analysis of Clinical Outcomes Between Neoadjuvant Chemoimmunotherapy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Multicenter, Retrospective Study

Background Patients with locally advanced esophageal squamous-cell carcinoma (LA-ESCC) generally experience poor prognosis after surgery. Neoadjuvant therapy has shown potential to improve survival outcomes. This study aimed to compare the long-term efficacy and safety of neoadjuvant chemoimmunotherapy (nCIT) versus neoadjuvant chemoradiotherapy (nCRT) in patients with LA-ESCC. Methods This multicenter study included patients with LA-ESCC treated at three hospitals in China between November 2015 and January 2024. Patients underwent either nCIT or nCRT followed by surgical resection. The primary endpoint was the 3-year overall survival (OS) rate. Secondary outcomes included objective response rate (ORR), pathologic complete response (pCR) rate, major pathologic response, disease-free survival (DFS), OS, and treatment-related adverse events. Propensity score matching was employed to adjust for baseline differences. Results A total of 225 LA-ESCC patients were included in this study, with 87 patients receiving nCRT and 138 patients receiving nCIT. After propensity score matching adjustment, each group have 87 patients included. The nCRT group demonstrated significantly superior outcomes to nCIT group in terms of ORR (85.06% vs. 45.98%, p < 0.001), T stage down rate (78.16% vs. 58.62%, p = 0.006), N stage down rate (85.06% vs. 45.98%, p < 0.001) and pCR rate (37.90% vs 14.90%, p < 0.001). The median follow-up duration was 44.5 months for the nCIT group and 35.1 months for the nCRT group. The nCIT group exhibited better 3-year OS (75.90% vs 55.60%, P < 0.05) andDFS (66.40% vs. 47.30%, P = 0.009) compared to the nCRT group. Subgroup analysis indicated that LA-ESCC patient with N + or non cT4 stage who received neoadjuvant chemoradiotherapy followed by esophagectomy had better OS and DFS. Univariate and multivariate Cox regression analyses identified clinical N stage as an independent prognostic factor for both OS and disease-free survival across both cohorts. Conclusion Neoadjuvant chemoimmunotherapy followed by esophagectomy is a promising treatment strategy for locally advanced resectable esophageal squamous cell carcinoma. nCRT may provide greater benefits in patients with N + or non-cT4 stage disease.