© The Author 2007. Published by Oxford University Press.
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Randomized Controlled Trial of Resection Versus Radiotherapy After Induction Chemotherapy in Stage IIIA-N2 Non–Small-Cell Lung Cancer
On behalf of the European Organisation for Research and Treatment of Cancer-Lung Cancer Group
Affiliations of authors: Department of Respiratory Medicine, University Hospital Ghent, Gent, Belgium (JPVM); Department of Radiation Therapy, Arnhem Radiotherapeutic Institute, Arnhem, The Netherlands (GWPMK); Departments of Respiratory Medicine and Thoracic Surgery, University Hospital Antwerp, Antwerp, Belgium (JPVM, PEYVS); European Organisation for Research and Treatment of Cancer Data Center, Brussels, Belgium (CL, CD); Departments of Pulmonology and Medical Oncology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands (EFS, GG); Department of Pulmonology, Sint Antonius Ziekenhuis, Nieuwegein, The Netherlands (FS); Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands (VCTH); Department of Pulmonology, Jeroen Bosch Ziekenhuis, ’s-Hertogenbosch, The Netherlands (BB); Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands (NvZ); Departments of Pulmonology and Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands (JPVM, TAWS)
Correspondence to: Jan P. van Meerbeeck, MD, PhD, Department of Respiratory Medicine, 7K12IE, University Hospital Ghent, De Pintelaan 185, 9000 Gent, Belgium (e-mail: jan.vanmeerbeeck{at}ugent.be).
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.
| CONTEXT AND CAVEATS Prior knowledge Compared with surgery alone, induction chemotherapy before surgery improves survival of patients with stage IIIA NSCLC. Study design A randomized controlled trial of surgery versus thoracic radiotherapy in patients with stage IIIA-N2 NSCLC who responded to induction chemotherapy. Contributions Median survival time and 5-year overall survival rates for patients who underwent surgery were 16.4 months and 15.7%; those for patients who underwent radiotherapy were 17.5 months and 14%. Implications In patients with stage IIIA-N2 NSCLC who respond to induction chemotherapy, subsequent surgery did not improve overall or progression-free survival compared with radiation therapy. Radiotherapy may be the preferred treatment for these patients, given its low morbidity and mortality. Limitations Patient selection may have been affected by changing standards for tumor staging during trial accrual. Outcome may have been affected by changing treatment standards during the trial.
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Gijs W. P. M. Kramer is deceased.
Manuscript received July 31, 2006; revised January 8, 2007; accepted January 29, 2007.
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J Natl Cancer Inst 2007 99: 1210.
J Natl Cancer Inst 2007 99: 415-418.
J Natl Cancer Inst 2007 99: 413.
J Natl Cancer Inst 2007 99: 413.
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