Neoadjuvant chemoradiotherapy vs. direct surgery for locally advanced esophageal cancer: a meta-analysis

Objective This meta-analysis systematically compares neoadjuvant chemoradiotherapy (nCRT) plus surgery vs. surgery alone for locally advanced esophageal cancer. Methods Randomized controlled trials (RCTs) were searched in PubMed, Embase, and Cochrane Library from inception to March 2025. Study selection, data extraction, and risk of bias assessment (using ROB 2.0) were performed independently. Pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS), and odds ratios (ORs) or relative risks (RRs) for R0 resection, pathological complete response (pCR), postoperative complications, and mortality were calculated using Stata 18.0. Heterogeneity was assessed with the I 2 statistic. Results Seven RCTs involving 1,168 patients were included. nCRT plus surgery significantly improved OS (HR = 0.68, 95% CI 0.59–0.77, P < 0.001) and DFS (HR = 0.59, 95% CI 0.50–0.67, P < 0.001) compared to surgery alone. The R0 resection rate showed a non-significant increase (OR=1.40, 95% CI 0.72–2.08, P = 0.32), while the pCR rate was significantly higher with nCRT (OR=8.42, 95% CI 4.88–14.52, P < 0.001). Postoperative complications were significantly higher in the nCRT plus surgery group (RR = 1.18, 95% CI 1.05–1.33, P = 0.006), while treatment-related mortality showed no significant difference (RR = 1.32, 95% CI 0.98–1.78, P = 0.065). Heterogeneity was low for OS and DFS (I 2 = 0%) and moderate for R0 resection (I 2 = 58.42%). Potential publication bias was detected for R0 resection. Conclusion nCRT followed by surgery significantly enhances survival outcomes and pCR rate, but does not significantly improve the R0 resection rate compared with surgery alone, without increasing mortality risk. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42025125423 , PROSPERO CRD420251251423.