Management of unresectable stage III non-small cell lung cancer: the role of combined chemoradiation.

Until the late 1980s, thoracic radiation therapy (TRT) was considered the standard of care for patients with stage III disease despite extremely poor 5-year survival rates. Several studies evaluating TRT combined with chemotherapy showed a survival advantage. Based on these data, combined modality therapy became accepted as the standard of care in this group of patients with good performance status and made the treatment of locally advanced non-small cell lung cancer (NSCLC) a multidisciplinary endeavor. Recent studies have shown that concurrent chemoradiotherapy offers a significantly greater survival advantage than sequential chemoradiotherapy and should be considered standard of care in stage III inoperable NSCLC. Although numerous Phase III trials have clearly demonstrated a survival benefit in those patients who receive combined modality therapy, many questions remain. The most effective combination of drugs, their optimal mode of administration, the use of either induction or consolidation therapy in addition to a backbone of concurrent therapy, and the details of TRT, including total dose, fractionation, acceleration, treatment volumes, and tumor targeting remain important issues to define. Although progress has been made in treatment for locally advanced NSCLC, the majority of patients still die within 5 years either from locoregional or distant progression of disease. This article will review the current data regarding treatment of this heterogeneous group of patients. In addition, a brief summary of new molecular therapies and chemotherapeutics will be presented.