Outcome of surgery versus radiotherapy after induction treatment in patients with N2 disease: systematic review and meta-analysis of randomised trials

Objective Chemoradiotherapy is often considered the 'standard of care' for patients with N2 disease. The aim was to evaluate survival outcomes of patients with N2 disease in multimodality trials of chemotherapy, radiotherapy and surgery. Methods Systematic review and meta-analyses (random and fixed effects) were performed. Searches of Medline and Embase (1980-2013) were conducted. Abstracts from thoracic scientific meetings were searched. Reference lists of all relevant studies were reviewed. All studies of patients with N2 disease who received induction chemotherapy or chemoradiotherapy and randomised to surgery or radiotherapy were included. No language restrictions were imposed. The main outcome was overall survival. Results 805 publications were identified. 519 and 281 were excluded because they were not primary results from randomised trials (or did not include N2 disease) or did not compare surgery with radiotherapy, respectively. The final six trials consisted of 868 patients. In four trials, patients received induction chemotherapy and in two trials patients received induction chemoradiotherapy. The HR comparing patients randomised to surgery after chemotherapy was 1.01 (95% CI 0.82 to 1.23; p=0.954) whereas for patients randomised to surgery after chemoradiotherapy was 0.87 (0.75 to 1.01; p=0.068). The overall HR of all pooled trials was 0.92 (0.81 to 1.03; p=0.157). Conclusions Surgery should be considered as part of multimodality treatment for patients with resectable lung cancer and ipsilateral mediastinal nodal disease. In trials where patients received surgery as part of trimodality treatment, overall survival was better than chemoradiotherapy alone.