Definitive Chemoradiotherapy Versus Trimodality Therapy for Resectable Oesophageal Carcinoma: Meta-analyses and Systematic Review of Literature

Background: Standard therapy for loco-regionally advanced, resectable oesophageal carcinoma is trimodality therapy (TMT) consisting of neoadjuvant chemoradiotherapy and oesophagectomy. Evidence of survival advantage of TMT over organ-preserving definitive chemoradiotherapy (dCRT) is inconclusive. The aim of this study is to compare survival between TMT and dCRT. Methods: A systematic review and meta-analyses were conducted. Randomised controlled trials and observational studies on resectable, curatively treated, oesophageal carcinoma patients above 18 years were included. Three online databases were searched for studies comparing TMT with dCRT. Primary outcomes were 1-, 2-, 3- and 5-year overall survival rates. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs and cohort studies. Quality of evidence was evaluated according to Grading of Recommendation Assessment, Development and Evaluation. Results: Thirty-two studies described in 35 articles were included in this systematic review, and 33 were included in the meta-analyses. Two-, three- and five-year overall survival was significantly lower in dCRT compared to TMT, with relative risks (RRs) of 0.69 (95% CI 0.57–0.83), 0.76 (95% CI 0.63–0.92) and 0.57 (95% CI 0.47–0.71), respectively. When only analysing studies with equal patient groups at baseline, no significant differences for 2-, 3- and 5-year overall survival were found with RRs of 0.83 (95% CI 0.62–1.10), 0.81 (95% CI 0.57–1.14) and 0.63 (95% CI 0.36–1.12). Conclusion: These meta-analyses do not show clear survival advantage for TMT over dCRT. Only a non-significant trend towards better survival was seen, assuming comparable patient groups at baseline. Non-operative management of oesophageal carcinoma patients might be part of a personalised and tailored treatment approach in future. However, to date hard evidence proving its non-inferiority compared to operative management is lacking.