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

For resectable esophageal cancer (EC), neoadjuvant therapy followed by radical surgery remains the standard pipeline. Controversy persists regarding optimal neoadjuvant regimens, especially among established standards including neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT), and emerging neoadjuvant immunochemotherapy (nICT). To address this, PubMed, Embase, Cochrane, and conferences were systematically searched for randomized controlled trials (RCTs) published until June 2025. Bayesian network meta-analyses and pairwise comparisons were performed to compare the pathological complete response (pCR) rate, overall survival (OS), and progression-free survival (PFS) by reporting the odds ratios (ORs) or hazard ratios (HRs) and 95% credible intervals (CrIs). As a result, 36 RCTs with 7,459 patients met the inclusion criteria. Compared with nCT, nCRT exhibited significant superiority in terms of pCR rates (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 also showed predominant advantages over nCT in achieving pCR (OR: 4.96, 95% CrI: 2.44-10.50). No significant difference in pCR was observed between nCRT and nICT (OR = 1.43, 95% CrI: 0.65-3.72). Subgroup analyses confirmed these robust benefits primarily in esophageal squamous cell carcinoma (ESCC) patients. However, due to sparse nICT data in esophageal adenocarcinoma (EAC), this subgroup derived benefit exclusively from nCRT versus nCT in terms of pCR (OR = 5.72, 95% CI: 2.17-15.09), without significant OS or PFS improvements. In conclusion, this study demonstrates the panoramic advantages of nCRT over nCT in EC across critical endpoints. Furthermore, nICT exhibits pCR rates comparable to those of nCRT, which establishes it as a potential alternative for ESCC, pending mature survival data.