Neoadjuvant Chemoimmunotherapy Versus Standard Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND: The long-term survival outcomes of neoadjuvant chemoimmunotherapy (NCIT) compared with neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) remain unclear. METHODS: Patients with LA-ESCC who underwent curative esophagectomy after receiving either NCRT or NCIT between June 2007 and December 2022 were retrospectively analyzed. The patients in the NCRT group received a uniform regimen of vinorelbine and cisplatin with concurrent radiotherapy, whereas those in the NCIT group received a PD-1 inhibitor combined with chemotherapy. Pathologic outcomes, overall survival (OS), and disease-free survival (DFS) were compared between the groups before and after application of inverse probability of treatment-weighting (IPTW). RESULTS: Overall, 462 patients were included (232 with NCIT; 230 with NCRT). The median follow-up period was 51.5 months (interquartile range, 33.0-87.0 months). The IPTW-adjusted analyses showed higher 3-year OS with NCIT versus NCRT (79.7 vs 68.2%; hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.28-0.91; P = 0.023). Multiple sensitivity analyses yielded consistent results. The 3-year DFS did not differ significantly between the two groups (73.9 vs 62.7%; HR, 0.65; 95% CI 0.40-1.05; P = 0.076). Pathologic complete response rates were comparable (NCIT, 33.6% vs NCRT, 41.0%; P = 0.229). Within 2 years postoperatively, NCIT had lower rates of overall recurrence (15.8 vs 28.8; P = 0.033) and distant metastases (6.6 vs 17.0%, P = 0.006) than NCRT, whereas the locoregional recurrence rate was similar (8.7 vs 11.8%; P = 0.592). CONCLUSIONS: In this retrospective cohort of selected patients with LA-ESCC who completed neoadjuvant therapy and underwent curative resection, NCIT was associated with better OS than NCRT.