Combined modality therapy of early stage nonsmall cell lung cancer

Therapy for locally advanced NSCLC has evolved into a multidisciplinary effort. Patients who are considered for this approach should undergo rigorous testing to accurately stage their disease. Patients with pleural effusions (with rare exception) are not candidates for intensive combined modality therapy. Appropriate patients for combined modality therapy should have a good performance status (generally Zubrod 0 or 1), adequate pulmonary function, absence of significant heart, lung, or other medical diseases, and be appropriate candidates for combination chemotherapy and thoracic surgery or thoracic radiotherapy. Several lessons can be learned from looking broadly at the phase II and phase III combined modality experience. The available data do not support the routine use of postoperative therapy in patients with completely resected disease. Treatment with chemotherapy before surgery or radiation has demonstrated survival benefit in patients with stage III disease. The French phase III trial of induction chemotherapy in patients with early stage disease found an 11-month improvement in overall survival (P = 0.15) and a significant increase in the risk of death for patients with stage I and II disease. The ongoing U.S. intergroup trial (SWOG 9900) and European trials will help to further define the role of chemotherapy in patients with clinical stage IB, II and IIIA NSCLC. Clinical trials should be conducted to compare preoperative chemoradiotherapy with preoperative chemotherapy. The recently completed intergroup 0139 trial (chemoradiation followed by surgery or not) should help to define whether surgery and radiation are required in the management of stage IIIA NSCLC. Finally, further improvement in survival with the use of "newer" cytotoxic agents seems unlikely as phase III trials in metastatic NSCLC have not demonstrated marked superiority over cispiatin-based regimens. Ongoing trials are assessing the incorporation of newer, biologic-based "targeted" therapies. Despite the dismal findings of trials of postoperative therapy, many patients continue to have surgery as their initial treatment followed by postoperative therapy. In contrast, trials with induction treatment seem to offer improved survival. It is time for a true multidisciplinary approach to the treatment of locally advanced NSCLC. Pulmonary physicians, thoracic surgeons, medical oncologists, and radiation oncologists should meet before the initiation of treatment to plan the most appropriate therapy for the individual patient.