A Prospective Multicenter Comparative Cohort Study of Neoadjuvant Sintilimab Plus Chemotherapy and Chemoradiotherapy in Resectable Clinical Node-Positive Esophageal Squamous Cell Carcinoma.

Abstract

Neoadjuvant chemoradiotherapy (CRT) remains the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC), although distant recurrence continues to limit long-term survival. Neoadjuvant chemoimmunotherapy (CIT) has emerged as a potential systemic-focused alternative. This prospective multicenter study explored the comparative outcomes of neoadjuvant sintilimab plus chemotherapy versus CRT in resectable, clinical node-positive ESCC. Consecutive adults with resectable, clinical node-positive (cN+) ESCC were enrolled across four academic centers. The patients received neoadjuvant sintilimab plus platinum-based chemotherapy (CIT) or standard CRT according to predefined institutional pathways in a nonrandomized design (2:1 enrollment). The primary endpoint was pathologic complete response (pCR). The secondary endpoints included nodal downstaging, perioperative outcomes, disease-free survival (DFS), overall survival (OS), and exploratory analyses of pretreatment inflammatory biomarkers. The 63 patients in this study completed neoadjuvant therapy followed by esophagectomy (CIT [n = 42] or CRT [n = 21]). The pCR rate was numerically higher with CRT than with CIT (52.4 % vs 31.0 %; p = 0.110). Nodal clearance was comparable (ypN0: 85.7 % vs 78.6 %; p = 0.735) with high R0 resection rates in both groups. During a median follow-up period of approximately 22 months, DFS did not differ significantly, whereas OS showed separation on unadjusted Kaplan-Meier analysis (p = 0.04, log-rank). Exploratory analyses showed no significant associations between pretreatment inflammatory biomarkers (neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], platelet-to-lymphocyte ratio [PLR], systemic immune-inflammation index [SII]) and pathologic response. Higher baseline SII was associated with OS in unadjusted comparisons. In this prospective nonrandomized cohort of clinical node-positive ESCC, CIT achieved nodal downstaging and R0 resection comparable with CRT but lower pCR. The observed survival difference should be interpreted cautiously and warrants validation in randomized trials.