The Role of Induction Therapy for Resectable Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer death among men and women in the US. Surgical resection is potentially curative; however, even after complete resection many patients experience systemic recurrence and subsequently die of their disease. As a means of reducing the chances of recurrence there has been significant interest in combining chemotherapy with surgical resection. Recently, several large phase III clinical trials have demonstrated a significant survival benefit with adjuvant or postoperative cisplatin-based chemotherapy. Use of preoperative or induction chemotherapy has also been an area of active investigation; however, the trials that have demonstrated a survival benefit were small in size, and there has not been widespread acceptance of this treatment approach. The trials of induction chemoradiotherapy have generally been performed in patients with locally advanced disease, frequently in patients with involvement of the level 2 mediastinal lymph nodes (N2). The results of the recent US Intergroup trial, 0139, which compared induction chemoradiotherapy followed by surgical resection versus nonsurgical therapy with chemoradiotherapy in patients with resectable stage IIIA-N2 disease, revealed equivalent overall survival between the two treatment approaches. The results of an unplanned subset analysis of patients who were treated with lobectomy in the surgical arm have generated significant interest and debate. When the strategy of induction therapy is used, pathological clearance of the mediastinal lymph nodes is a significant prognostic factor for overall survival. Current investigations are attempting to determine the optimal method of assessing this critical prognostic factor. The toxicity, efficacy and proper selection of patients for induction therapy, particularly induction chemoradiotherapy, will be assessed in ongoing and future clinical trials.