Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis

Background Resectable oesophageal cancer is often treated with surgery alone or with preoperative (neoadjuvant) chemoradiotherapy or chemotherapy. We aimed to clarify the benefits of neoadjuvant chemoradiotherapy or chemotherapy versus surgery alone by a meta-analysis of randomised trial data. Methods Eligible trials were identified first from earlier published meta-analyses and systematic reviews. We also used MEDLINE, Cancerlit, and EMBASE databases to identify additional studies and published abstracts from major scientific meetings since 1980. Only randomised studies with an analysis by an intention-to-treat principle were included, and searches were restricted to those databases citing articles in English. We used published hazard ratios if available or estimates from other survival data or survival curves. Treatment effects by type of tumour and treatment sequencing were also investigated. Findings Ten randomised comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1209) and eight of neoadjuvant chemotherapy versus surgery alone (n=1724) in patients with local operable oesophageal carcinoma were identified. The hazard ratio for all-cause mortality with neoadjuvant chemoradiotherapy versus surgery alone was 0.81 (95% CI 0.70-0.93; p=0.002), corresponding to a 13% absolute difference in survival at 2 years, with similar results for different histological tumour types: 0.84 (0.71-0.99; p=0.04) for squamous-cell carcinoma (SCC), and 0.75 (0.59-0.95; p=0.02) for adenocarcinoma. The hazard ratio for neoadjuvant chemotherapy was 0.90 (0.81-1.00; p=0.05), which indicates a 2-year absolute survival benefit of 7%. There was no significant effect on all-cause mortality of chemotherapy for patients with SCC (hazard ratio 0.88 [0.75-1.03]; p=0.12), although there was a significant benefit for those with adenocarcinoma (0.78 [0.64-0.95]; p=0.014). Interpretation A significant survival benefit was evident for preoperative chemoradiotherapy and, to a lesser extent, for chemotherapy in patients with adenocarcinoma of the oesophagus. The findings provide an evidence-based framework for the use of neoadjuvant treatment in management decisions.