Neoadjuvant Immunochemoradiation Therapy Versus Chemoradiation Therapy in Esophageal Cancer: A Systematic Review and Meta-Analysis of Reconstructed Individual Patient Data.

Abstract

Neoadjuvant immunochemoradiation therapy (nICRT) is emerging as a promising treatment for resectable esophageal cancer, but comprehensive analyses comparing it with standard neoadjuvant chemoradiation therapy (nCRT) are limited. This meta-analysis aimed to evaluate the efficacy, safety, and survival outcomes of nICRT versus nCRT. A systematic search of PubMed, Embase, the Cochrane Library, and major conference proceedings up to October 30, 2024, identified studies involving resectable esophageal cancer treated with nICRT or nCRT. Data on pathologic complete response, major pathologic response, treatment-related adverse events, overall survival (OS), and progression-free survival were extracted. A one-stage meta-analysis using reconstructed individual patient data was performed, calculating hazard ratios with 95% CIs. Thirty-seven studies were included, comprising 811 patients treated with nICRT and 1796 with nCRT. nICRT demonstrated significantly longer OS than nCRT (hazard ratio, 0.714; 95% CI, 0.550-0.926; P = .011). The 1-, 2-, and 3-year OS rates were 89.9%, 76.0% and 66.4%, respectively, for nICRT, compared with 85.0%, 66.5%, and 57.3% for nCRT. The pathologic complete response rate was significantly higher in nICRT (50% vs 38%; P = .040) for squamous cell carcinoma. Safety profiles were comparable, with no significant differences in grades 3 and 4 treatment-related adverse events or postoperative complications between the groups. nICRT showed potential for superior survival compared with standard nCRT in resectable esophageal cancer and showed enhanced pathologic response in squamous cell carcinoma, with a possibly acceptable safety profile. These findings support future trials integrating immunotherapy into neoadjuvant treatment regimens for esophageal cancer.