Induction Therapies Plus Surgery Versus Exclusive Radiochemotherapy in Stage IIIA/N2 Non–Small Cell Lung Cancer (NSCLC)

In spite of the growing body of data from prospective randomized clinical trials (PRCTs) and meta-analyses, the optimal treatment approach in patients with stage IIIA non–small cell lung cancer remains unknown. This review focuses on the available data directly confronting induction chemotherapy or induction radiochemotherapy (RT-CHT) when followed by surgery with exclusive RT-CHT. Seven PRCTs and 4 meta-analyses investigated this issue. In addition, numerous retrospective studies attempted to identify potential predictors and/or prognosticators that may have influenced the decision to offer surgery in a particular patient subgroup. Several retrospective studies also evaluated exclusive RT-CHT in this setting. There is not a single piece of the highest level of evidence (PRCT or MA) showing any advantage of induction therapies followed by surgery over exclusive RT-CHT with the former treatment option leading to significantly more morbidity and mortality. Although several studies attempted to identify patient subgroups favoring induction therapies followed by surgery, they have invariably been retrospective in nature, and their results have never been reproduced even in other retrospective setting. Furthermore, no PRCT investigated potential pretreatment patient and/or tumor-related predictors of surgical multimodality success. Exclusive RT-CHT achieves similar results to induction therapies followed by surgery but with less morbidity and mortality. This is accompanied with the finding that no pretreatment predictor exists to enable identification of even a subgroup of stage IIIA/pN2 patients benefiting from any surgical approach.