Combined modality treatment for locally advanced non-small cell lung cancer--which control arm?

Up to one-third of newly diagnosed patients with non-small cell lung cancer (NSCLC) present with locally advanced, unresectable disease. Traditionally, these patients have been treated with thoracic radiotherapy alone. Unfortunately, the vast majority eventually die as a result of the development of distant, extrathoracic metastases. While chemotherapy is not particularly effective against clinically obvious metastatic disease, there are good theoretical reasons why the use of this modality in earlier stage disease may be beneficial. Several recently completed pilot studies of combined modality therapy have yielded promising results suggesting improved survival. Indeed, the combination of chemotherapy and thoracic radiotherapy has been shown to be marginally superior to radiotherapy alone in a few recently completed randomized trials. However, this has not been a uniform observation. Thus, further study is needed to firmly establish the role of combined modality treatment in Stage III, unresectable non-small cell lung cancer. In these future trials, the best control arm is a matter of some controversy.