Definitive radiochemotherapy versus surgery within multimodality treatment in stage III non-small cell lung cancer (NSCLC) - a cumulative meta-analysis of the randomized evidence

Randomized trials were analyzed comparing surgery with definitive radiotherapy as local curative treatment options within the framework of different multimodality treatments for patients with locally advanced non-small cell lung cancer (NSCLC). Endpoints for comparison of treatment results were overall survival, progression-free survival, and toxicity. Hazard ratios (HR) were taken to measure treatment effects and pooled using a random effects model. Overall survival was not significantly different between surgical and definitive radiotherapy arms (HR=0.92 [95%CI 0.82-1.04], p=0.19, χ(2)-test). There was heterogeneity with respect to survival at 2 years (p<0.0001, Cochran Mantel Haenszel (CMH)-test). Latter trials using concurrent radiochemotherapy (ccRT/CT) showed better survival at 2 years (risk ratio of death=0.80 [95%CI 0.73-0.88], p<0.0001, CMH-test). In the ccRT/CT trials, survival in the surgical arms tended to have an excess early mortality before 6 months of follow-up and a lesser hazard rate in comparison to definitive ccRT/CT thereafter (HR=0.78 [95%CI 0.63-0.98]). Over all trials, treatment associated mortality was higher in the surgical arms (risk ratio=3.56 [95% CI: 1.65-7.72], p=0.0005, CMH test). With respect to progression-free survival, no significant differences were found (HR=0.91 [95%CI: 0.73 - 1.13]), although the largest conducted trial found an advantage for the surgical arm (HR=0.77 [95%CI: 0.62-0.96]). Induction therapy followed by resection or definitive radiochemotherapy represent valuable curative treatment options for patients with stage III NSCLC, the individual treatment choice deserves careful interdisciplinary evaluation and counseling. Based on the broad heterogeneity of patient groups in these stages further research on predictive factors supporting individual therapy selection is necessary.