Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis

Background In a previous meta-analysis, we identified a survival benefit from neoadjuvant chemotherapy or chemoradiotherapy before surgery in patients with resectable oesophageal carcinoma. We updated this meta-analysis with results from new or updated randomised trials presented in the past 3 years. We also compared the benefits of preoperative neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy. Methods To identify additional studies and published abstracts from major scientifi c meetings, we searched Medline, Embase, and Central (Cochrane clinical trials database) for studies published since January, 2006, and also manually searched for abstracts from major conferences from the same period. Only randomised studies analysed by intention to treat were included, and searches were restricted to those databases citing articles in English. We used published hazard ratios (HRs) if available or estimates from other survival data. We also investigated treatment effects by tumour histology and relations between risk (survival after surgery alone) and effect size. Findings We included all 17 trials from the previous meta-analysis and seven further studies. 12 were randomised comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1854), nine were randomised comparisons of neoadjuvant chemotherapy versus surgery alone (n=1981), and two compared neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy (n=194) in patients with resectable oesophageal carcinoma; one factorial trial included two comparisons and was included in analyses of both neoadjuvant chemoradiotherapy (n=78) and neoadjuvant chemotherapy (n=81). The updated analysis contained 4188 patients whereas the previous publication included 2933 patients. This updated meta-analysis contains about 3500 events compared with about 2230 in the previous meta-analysis (estimated 57% increase). The HR for all-cause mortality for neoadjuvant chemoradiotherapy was 0.78 (95% CI 0.70-0.88; p<0.0001); the HR for squamous-cell carcinoma only was 0.80 (0.68-0.93; p=0.004) and for adenocarcinoma only was 0.75 (0.59-0.95; p=0.02). The HR for all-cause mortality for neoadjuvant chemotherapy was 0.87 (0.79-0.96; p=0.005); the HR for squamous-cell carcinoma only was 0.92 (0.81-1.04; p=0.18) and for adenocarcinoma only was 0.83 (0.71-0.95; p=0.01). The HR for the overall indirect comparison of all-cause mortality for neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy was 0.88 (0.76-1.01; p=0.07). Interpretation This updated meta-analysis provides strong evidence for a survival benefit of neoadjuvant chemoradiotherapy or chemotherapy over surgery alone in patients with oesophageal carcinoma. A clear advantage of neoadjuvant chemoradiotherapy over neoadjuvant chemotherapy has not been established. These results should help inform decisions about patient management and design of future trials.