Efficacy among neoadjuvant therapy for resectable esophageal cancer: A systematic review and network meta-analysis of randomized controlled trials

For resectable esophageal cancer (EC), neoadjuvant therapy followed by radical surgery remains the standard pipeline, but optimal regimens remain debated among established standards include neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (nCT), and emerging neoadjuvant immunochemotherapy (nICT). PubMed, Embase, Cochrane, and conferences were searched for randomized controlled trials (RCTs) published until June 2025. Bayesian network meta-analyses and pairwise comparisons were performed to compare pathological complete response (pCR) rate, overall survival (OS) and progression-free survival (PFS) by reporting odds ratio (OR) or hazard ratio (HR) and 95% credible intervals (CrIs).Thirty-six RCTs with 7459 patients were included. Versus nCT, nCRT showed superior pCR (OR = 7.03, 95% CrI: 4.17-15.05), OS (HR = 0.78, 95% CrI: 0.69-0.88) and PFS (HR = 0.83, 95% CrI: 0.72-0.95). nICT outperformed nCT in pCR (OR: 4.96, 95% CrI: 2.44-10.50), with no significant pCR difference between nCRT and nICT (OR = 1.43, 95% CrI: 0.65-3.72). Subgroup analyses confirmed consistency in esophageal squamous cell carcinoma, but esophageal adenocarcinoma benefited only in pCR with nCRT. In conclusion, nCRT demonstrates advantages over nCT across endpoints, while nICT shows non-inferior pCR versus nCRT, supporting its role as a first-line alternative.