Early-stage non-small-cell lung cancer: current perspectives in combined-modality therapy.

The most effective treatment for patients with early-stage non-small-cell lung cancer (NSCLC) remains complete surgical resection, providing the disease is medically operable and adequately staged. The effectiveness of surgical resection, however, is limited by high rates of distant recurrence caused by the presence of metastatic disease that is not apparent at the time of surgery. Thus, induction, adjuvant chemotherapy, and radiation therapy, as well as a combination of both, have been studied for their ability to reduce local and distant recurrence rates and to improve survival. Adjuvant chest radiation therapy following resection decreases local relapse rates but also decreases overall patient survival, with an increase in the hazard ratio of death. A previous metaanalysis of cisplatin-based adjuvant chemotherapy showed a 13% reduction in the hazard ratio of death and a 5% improvement in 5-year survival, but the differences in the small sample failed to reach statistical significance. Newer 2-drug combinations were shown to reduce the hazard ratio of death by 14%, with a 4.3% improvement in 5-year survival in the largest trial recently reported. These newer 2-drug combinations also have the benefits of reduced toxicity and improved delivery. Induction chemotherapy offers several potential advantages compared with adjuvant chemotherapy, such as improved delivery, early control of micrometastatic disease, and reduction of the primary tumor size prior to surgery, thus allowing for more conservative and possibly complete resection of the tumor. A number of clinical trials have shown that induction chemotherapy is safe and feasible, with no significant increase in surgical complications, and results in favorable survival rates in patients with resectable NSCLC. A number of phase III randomized trials are currently under way to confirm the benefits of induction chemotherapy in patients with stage IB-IIIA NSCLC and to compare induction chemotherapy versus adjuvant chemotherapy following surgery versus surgery alone. In addition, biologically targeted agents are currently under study for patients with advanced NSCLC.