Risk factors for recurrence in patients with resected N1 non-small cell lung cancer - a systematic review and meta-analysis.

PURPOSE To evaluate the rates of locoregional failure (LRF) vs distant metastasis (DM), and find risk factors for recurrence in patients with completely resected N1 non-small cell lung cancer (NSCLC). METHODS By searching Pubmed, Embase and the Cochrane Controlled Trials Register from 1995 through 2014, eligible randomized clinical trials (RCTs) were identified. In addition, the reference lists of articles and conference abstracts were searched. The logarithm of the risk ratio (RR) and its standard error (SE) were calculated, and a fixed-effect model was used to combine the estimates. RESULTS 3 RCTs and 9 retrospective studies, which included 889 patients, were identified and selected. All studies dealt with resected N1 NSCLC, LRF vs DM, and risk factors such as visceral pleural invasion (VPI) and lymphovascular invasion (LVI). There was statistically significant benefit on 5-year overall survival (OS) for LRF (RR=0.68,95% CI=0.60-0.78, p<0.00001). Further analysis for patients with LRF also showed that VPI (RR=1.25, 95% confidence interval/CI=1.09-1.42, p=0.0009), LVI (RR=1.16, 95% CI=1.04-1.30, p=0.009), were the main risk factors for recurrence. CONCLUSIONS The present study indicates that in patients with resected N1 NSCLC, the incidence of LRF is lower than DM. Advanced T stage classification, VPI, and LVI were predictors of poor survival. These patients represent a subgroup with N1 disease who might benefit from additional therapy, including adjuvant radiotherapy (RT). However, large, well-designed prospective studies should be conducted to confirm this conclusion.