Combined modality treatment of non-small-cell lung cancer

Among all nonmetastatic non-small-cell lung cancer (NSCLC) patients, the best survival rates are observed in patients who undergo surgery. Nevertheless, 5-year survival rates vary between 20% and 60% depending on the stage of the disease. Several combined modality treatments have been investigated to improve outcome in localized NSCLC. These include local treatment, systemic before local treatment, concomitant systemic and local treatments, and systemic after local treatment. Preoperative irradiation was shown to be of no benefit on local recurrence rates or overall survival. Even doses of radiation >/=40 grays (Gy) were associated with lower survival rates. Postoperative irradiation did not influence survival in stage III disease and seemed to be deleterious in stages I and II disease. Modern radiotherapy techniques might be of interest in this setting but have been insufficiently tested. The early phase III studies of preoperative chemotherapy versus primary surgery in stage III NSCLC showed a tremendous difference in favor of chemotherapy. A larger study did not confirm these results but suggested that preoperative chemotherapy might have a greater effect in stages I and II of the disease. In locally advanced disease, chemotherapy followed by radiotherapy was shown to increase survival when compared with radiotherapy alone. Studies comparing concurrent chemoradiation with radiotherapy only were in favor of the concomitant schedule, which improved local control. Promising results have been reported with chemoradiation followed by surgery in stage IIIa and even stage IIIb disease. Randomized studies of postoperative chemotherapy demonstrated a 5% improvement in 5-year survival over adjuvant-free treatment. Postoperative chemoradiation showed no advantage over postoperative radiotherapy. Several trials that are ongoing or whose accrual was recently completed should further define the role of perioperative chemotherapy in resectable NSCLC and of trimodality treatments in advanced disease. Targeted agents are being developed in the postoperative setting. New schedules of chemoradiation with higher therapeutic indexes are also being investigated in nonresectable stage III NSCLC.