Combined modality therapy for stage III non-small cell lung cancer

Lung cancer remains the leading cause of cancer death in the U.S. among both men and women. Approximately 45% of patients present with stage III disease. A proportion of these patients is amenable to surgical resection; however, the majority are "unresectable." For patients with unresectable stage IIIA/B disease, thoracic radiation therapy (TRT) was considered the standard of care until the late 1980s despite a very poor 5-year survival rate. Several clinical trials demonstrated that the combination of chemotherapy and TRT was superior to TRT alone. Based on these data, combined modality therapy became the standard of care for patients with good performance status. Recent trials have shown that concurrent chemoradiotherapy offers a significant survival advantage over sequential chemoradiotherapy. Despite a substantial number of clinical trials, important questions on the optimal treatment paradigm remain. The most effective chemotherapy combination, the use of induction or consolidation chemotherapy in addition to the concurrent portion of therapy, and the optimal dose of chemotherapy with concurrent TRT have yet to be determined. The optimal total dose, fractionation, acceleration, treatment volume, and tumor targeting remain questions related to the TRT portion of therapy. Although significant progress has been made, the majority of patients experience locoregional or distant progression of their disease and die within 5 years of diagnosis. Thus, continued development and participation in clinical trials is crucial to further improvements in the treatment of patients with stage III disease.