Challenges of preoperative chemotherapy in non-small cell lung cancer

Surgical extirpation of a non-small cell lung cancer (NSCLC) represents an individual's best opportunity for cure. Unfortunately, only a small percentage of patients present with surgically resectable disease. Many patients are diagnosed with tumor confined to the thorax but which is technically unresectable. In the setting of locally advanced disease, combination chemotherapy is capable of effecting tumor shrinkage in a majority of cases. When this occurs, it is tempting to subject the patient to thoracotomy in an attempt to resect the previously unresectable lesion. Use of chemotherapy in this manner is generally referred to as neoadjuvant or preoperative chemotherapy. Recently, several groups have demonstrated that such an approach is feasible but the impact on patient survival remains ill defined. Further studies designed to ascertain the feasibility of neoadjuvant chemotherapy are no longer warranted. It is time for a prospective, randomized trial designed to determine the true potential of neoadjuvant chemotherapy. The optimal design of such a trial is a matter of debate but several options are reasonable. This article will review the available data on preoperative chemotherapy in locally advanced non-small cell lung cancer and will review areas of controversy.