Perioperative chemotherapy or preoperative chemoradiotherapy in patients with esophageal carcinoma: A systematic review and meta-analysis.

Abstract

e16105 Background: Despite advances in treatment options, esophageal carcinoma remains a disease with poor prognosis with a low 5-year survival rate and a high recurrence rate even after curative resection. RCTs have established that both perioperative chemotherapy (CT) and preoperative chemoradiotherapy (CRT) are superior to surgery alone; however, the optimal approach between CT versus CRT for esophageal carcinoma remains debated. Furthermore, data from recently published high quality trials have not been incorporated in prior quantitative syntheses. This meta-analysis compares the safety and efficacy of CT versus CRT in resectable esophageal and gastroesophageal junction carcinoma including subgroup analyses integrating recently available evidence. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. 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. Risk of bias was assessed using the Cochrane Risk of Bias Version 2.0 (RoB 2.0) tool across five domains. 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. Statistical heterogeneity was assessed using the Chi-square test and quantified with the I 2 statistic. Results: Eight RCTs comprising 2,277 patients 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, surgical complications 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. Conclusions: By incorporating data from the most recent RCTs, our 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 and molecular profiling to identify more effective patient subgroups that may benefit most from either approach in future research.