Neoadjuvant Treatment for Resectable, Stage IIIA Non-Small Cell Lung Cancer

The optimal treatment of patients with stage IIIA non-small cell lung cancer (NSCLC) remains highly controversial. In resectable stage IIIA NSCLC, there is still a considerable debate regarding the best strategy. Treatment choice is often a function of institutional and/or physician preference. Treatment consists of neo-adjuvant chemotherapy or chemoradiotherapy (CHRT) followed by surgery with or without postoperative radiotherapy (RT), definitive CHRT, or neoadjuvant immunotherapy followed by surgery and several other options. Neo-adjuvant therapy for operable NSCLC has been the subject of a large number of studies in the literature. We summarized existing data and also highlight ongoing trials, focusing on neoadjuvant immunotherapy. Neoadjuvant CHRT seems to be safe and efficient and is associated with an improved pathological outcome, but it has failed to demonstrate any advantage in terms of progression-free survival or overall survival compared to neoadjuvant chemotherapy. Contrary to previous fears, radiotherapy does not add a higher toxicity, nor does it increase post-operative mortality compared to chemotherapy alone. Studies with chemoimmunotherapy provide a higher rate of pathologic responses and downstaging compared to chemotherapy. On the other hand, it remains to be confirmed whether pCR is a sufficient surrogate for OS. Results of ongoing neoadjuvant immunotherapy trials are awaiting and we believe, the next decades will bring much needed improvements for patients. Still the controversy is not being solved and further trials considering a better patients’ selection, innovative radiotherapy and more efficient systemic treatments need to be undertaken.