Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Patients with Esophageal Carcinoma: A Systematic Review and Meta-Analysis

Background The optimal approach between perioperative chemotherapy (CT) versus preoperative chemoradiotherapy (CRT) for esophageal carcinoma remains debated. This meta-analysis compares the safety and efficacy of CT versus CRT in resectable esophageal and gastroesophageal junction carcinoma. Methods Electronic databases were systematically searched for eligible randomized controlled trials (RCTs) that enrolled adult patients (aged ≥ 18 years) with histologically confirmed, resectable esophageal or gastroesophageal junction carcinoma, directly compared perioperative CT with preoperative CRT, and reported at least one outcome of interest. Meta-analysis was conducted using RevMan 5.4 with a random-effects model. Hazard Ratios (HRs) were pooled for time-to-event outcomes, and risk ratios (RR) for dichotomous endpoints. Results Eight RCTs were included. Compared with CRT, CT had significantly reduced R0 resection rates (RR 0.94, 95% CI 0.89, 0.99) and a lower pathologic complete response (RR 0.27, 95% CI 0.13, 0.58). No statistically significant differences were observed in overall survival, progression-free survival, postoperative mortality, or severe adverse events. There was a trend toward greater benefit of CRT in squamous cell carcinoma; however, the test for subgroup differences did not attain statistical significance. Conclusion This meta-analysis suggests that CRT improves local tumor control by increasing R0 resection rates and complete response rates, but without a clear survival advantage over CT. This meta-analysis further highlights the need for an updated multidisciplinary framework and highlights the importance of biomarker-driven strategies in future research.