Is the evidence in favour of neoadjuvant chemotherapy in stage IIIA (N2) non-small cell lung cancer solid enough?

In stage IIIA (N2) non-small cell lung cancer, single modality therapy with either surgery or radiation is curative in very few cases. The rationale behind neoadjuvant chemotherapy lies in the eradication of micrometastatic disease, which is often present when ipsilateral mediastinal or subcarinal lymph nodes (N2) are involved. Several studies have addressed the feasibility and efficacy of preoperative chemotherapy followed by surgery. All of these induction chemotherapy trials have reported a high radiographic response rate, high resectability rate and improved survival in completely resected patients. The findings reported in three published randomized trials indicate that the survival rate of stage IIIA patients is better with induction chemotherapy plus surgical resection than with resection alone. Phase II trials using preoperative concurrent chemoradiotherapy have been tested with encouraging results. Combined modality treatment in locally advanced non-small cell lung cancer continues to evolve and is the subject of ongoing research. New chemotherapeutic agents should be integrated into the neoadjuvant setting to improve results. A better understanding of the biology of tumours could well help in the optimization of these new agents. No doubt, in the future, molecular classification of non-small cell lung cancer will provide a useful tool for making therapy-related decisions.