Efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in locally advanced esophageal cancer: An updated meta-analysis

Background: Currently, the optimal treatment for neoadjuvant therapy for locally advanced esophageal cancer is not clear, and there is no evidence that neoadjuvant chemoradiotherapy (nCRT) is superior to neoadjuvant chemotherapy (nCT). Due to the publication of new clinical trials and defects in previous meta-analyses, we conducted an updated meta-analysis to evaluate the efficacy and safety of nCRT and nCT. Methods: The following databases were searched for studies: PubMed, EMBASE, and Cochrane library (updated to April 22, 2023). All randomized trials comparing nCRT with nCT in locally advanced esophageal cancer met the inclusion criteria. Data were analyzed using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes assessed from the trials included overall survival (OS), progression-free survival (PFS), pathological complete response (pCR), R0 resection rate, postoperative complications, postoperative mortality, and grade 3 or higher adverse events (3 + AEs). Results: This systematic review and meta-analysis included 7 randomized controlled studies involving 1372 patients (686 receiving nCRT and 686 receiving nCT). Compared with nCT, nCRT significantly improved OS (HR = 0.80; 95% CI: 0.68-0.94), PFS (HR = 0.78; 95% CI: 0.66-0.93), pCR (OR = 13.00; 95% CI: 7.82-21.61) and R0 resection (OR = 1.84; 95% CI: 1.32-2.57), but was associated with higher postoperative mortality (OR = 2.31; 95% CI: 1.26-4.25) and grade 3 + AEs (OR = 2.21; 95% CI: 1.36-3.58). There was no significant difference in postoperative complications between nCRT and nCT (OR = 1.15; 95% CI: 0.82-1.61). Subgroup analysis showed significant survival benefit in squamous cell carcinoma (HR = 0.80; 95% CI: 0.68-0.98), but not in adenocarcinoma (HR = 0.80; 95% CI: 0.63-1.08). Conclusions: Our meta-analysis found superior efficacy associated with nCRT compared with nCT in both tumor regression and prolonged survival, but increased the risk of postoperative mortality and grade 3 + AEs. Esophageal squamous cell carcinoma was more likely to benefit from nCRT than esophageal adenocarcinoma in the term of OS.