Randomized Controlled Trial of Resection Versus Radiotherapy After Induction Chemotherapy in Stage IIIA-N2 Non–Small-Cell Lung Cancer

• Published in: JNCI : Journal of the National Cancer Institute 2007-03, Vol.99 (6), p.442-450
• Main Authors: van Meerbeeck, Jan P., Kramer, Gijs W. P. M., Van Schil, Paul E. Y., Legrand, Catherine, Smit, Egbert F., Schramel, Franz, Tjan-Heijnen, Vivianne C., Biesma, Bonne, Debruyne, Channa, van Zandwijk, Nico, Splinter, Ted A. W., Giaccone, Giuseppe
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - radiotherapy; Carcinoma, Non-Small-Cell Lung - surgery; Chemotherapy; Chemotherapy, Adjuvant; Clinical outcomes; Clinical trials; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - radiotherapy; Lung Neoplasms - surgery; Male; Medical sciences; Medical treatment; Middle Aged; Neoplasm Staging; Organoplatinum Compounds - administration & dosage; Pneumology; Pneumonectomy; Prospective Studies; Radiation therapy; Radiotherapy, Adjuvant; Remission Induction - methods; Thoracic surgery; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djk093

Background Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non–small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy. Methods Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan–Meier analyses from time of randomization. Results Induction chemotherapy resulted in a response rate of 61% (95% confidence interval [CI] = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups. Conclusion In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients.