Neoadjuvant immunochemotherapy for locally advanced esophageal squamous cell carcinoma in real-world practice: an analysis of the clinical outcomes and long-term survival, and the feasibility of using major pathological response as a surrogate endpoint

BACKGROUND: Neoadjuvant immunochemotherapy is expected to become the standard treatment mode for locally advanced esophageal squamous cell carcinoma (ESCC). This study aims to analyze the clinical outcomes and long-term survival of neoadjuvant immunochemotherapy for locally advanced ESCC, and explore the feasibility of using major pathological response (MPR) as a surrogate endpoint. METHODS: This real-world retrospective study consecutively included eligible patients with stage II-IVA locally advanced ESCC who received neoadjuvant immunochemotherapy and surgery between 2019 and 2022 at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine. RESULTS: This study collected a total of 166 patients, and ultimately included 126 patients after screening. The objective response rate (ORR) was 69.8% (88/126). The incidence of grade 3-4 adverse events (AEs) was 13.5% (17/126). MPR was observed in 49 (38.9%) patients, and 24 (19.0%) patients achieved a complete pathological response (pCR). The median progression-free survival (PFS) was 31.7 months and the 3-year PFS rate was 56.3%. The median overall survival (OS) was not reached and the 3-year OS rate was 70.6%. The median PFS of the non-MPR group was 25.0 months, with the MPR group not achieved (hazard ratio [HR], 2.503; 95% CI 1.359-4.610; P = 0.0022). The median OS in the non-MPR group was 31.7 months and not reached in the MPR group (HR, 3.607; 95% CI 1.576-8.254; P = 0.0012). MPR is an independent prognostic factor affecting OS (HR, 2.522; 95% CI 1.018-6.401; P = 0.046). CONCLUSIONS: Neoadjuvant immunochemotherapy is safe and effective for locally advanced ESCC, and can result in certain survival benefits. MPR can serve as a surrogate endpoint for predicting long-term OS.