Survival Impact of Adjuvant Nivolumab Therapy for Locally Advanced Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Chemotherapy with Docetaxel Plus 5-Fluorouracil and Cisplatin.

Abstract

The efficacy of adjuvant nivolumab following neoadjuvant chemotherapy in managing locally advanced esophageal cancer remains unclear. This study evaluated the survival benefits of adjuvant nivolumab after neoadjuvant chemotherapy with a docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen in patients with locally advanced esophageal squamous cell carcinoma (ESCC). This single-center, retrospective study included 439 consecutive patients with locally advanced ESCC who underwent radical esophagectomy following neoadjuvant DCF chemotherapy. The approval of adjuvant nivolumab has led to patients with pathological lymph node metastasis following preoperative treatment becoming eligible for treatment. Among the 439 patients included, 379 and 60 received neoadjuvant DCF (neoDCF group) and adjuvant nivolumab after neoadjuvant DCF (neoDCF+AdNivo group), respectively. Disease-free survival (DFS) remained comparable despite differences in pathological lymph node metastasis (53% vs. 100%). After propensity score matching, adjuvant nivolumab yielded a significant improvement in DFS and overall survival (OS) (2-year DFS: 60.2% vs. 44.9%, hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.28-0.83, p = 0.009; 2-year OS: 94.1% vs. 64.0%, HR 0.17, 95% CI 0.06-0.50, p = 0.001). The 1-year postoperative recurrence rate in the neoDCF+AdNivo group was lower (23% vs. 47%, p = 0.007). Subgroup analysis revealed a marked improvement in DFS in patients with ypT3 or ypN2 disease, particularly in those with ypStage III disease. Adjuvant nivolumab and ypN stage were identified as independent prognostic factors for DFS. Adjuvant nivolumab therapy following neoadjuvant DCF chemotherapy may improve survival outcomes in patients with locally advanced ESCC, with particularly strong benefits being observed in ypStage III.