Multimodality Treatment of Stage IIIA/N2 NSCLC: Why Always NO to Surgery?

The highest level of evidence from prospective randomized clinical trials (PRCTs) and meta-analyses (MAs) which have asked the question about optimal treatment approach in patients with Stage IIIA/pN2 non-small cell lung cancer (NSCLC) accumulated slowly in the past 25 years. They have mostly focused on the question of induction chemotherapy (CHT) or induction radiochemotherapy (RT-CHT) both followed by surgery and frequently compared it with exclusive RT-CHT. Seven PRCTs and five MAs which currently exist have investigated this issue. None of them showed any benefit for surgical multimodality approach over exclusive RT-CHT, except an unplanned, post-hoc analysis coming from a single PRCT, which concerned lobectomy-suitable candidates. While there are many retrospective studies which tried to identify patient subgroups favoring induction therapies followed by surgery, their results have never been reproduced even in retrospective setting. Importantly, no PRCT ever investigated potential pretreatment patient and/or tumor-related predictors favoring surgical multimodality and it remained unknown which, if any, patients may actually benefit from surgical multimodality approach. Exclusive RT-CHT achieves similar results to induction therapies followed by surgery but with less morbidity and mortality. Together with the lack of identified pretreatment predictors pointing towards surgery, they suggest that surgical bi- or trimodality approach should not be practiced outside well planned clinical trial.