Long-Term Survival Associated With Complete Resection After Induction Chemotherapy in Stage IIIA (N2) and IIIB (T4N0-1) Non–Small-Cell Lung Cancer Patients: The Spanish Lung Cancer Group Trial 9901 Pilar Garrido, José Luis Gonza ´lez-Larriba, Amelia Insa, Mariano Provencio, Antonio Torres, Dolores Isla, José Miguel Sanchez, Felipe Cardenal, Manuel Domine, Jose Ramon Barcelo, Vicente Tarrazona, Andres Varela, Rafael Aguilo, Julio Astudillo, Ignacio Muguruza, Angel Artal, Florentino Hernando-Trancho, Bartomeu Massuti, Maria Sanchez-Ronco, and Rafael Rosell A B S T R A C T Purpose To assess the activity of induction chemotherapy followed by surgery in stage IIIA and selected stage IIIB non–small-cell lung cancer patients. Patients and Methods Mediastinoscopy proof of either positive N2 (IIIA) or T4N0-1 (IIIB) disease was required. Induction therapy was three cycles of cisplatin/gemcitabine/docetaxel, followed by surgery. Results From December 1999 to March 2003, 136 patients were entered onto the study; the clinical response rate in 129 assessable patients was 56%. The overall complete resection rate was 68.9% of patients eligible for surgery (72% of stage IIIA patients and 66% of stage IIIB patients) and 48% of all assessable patients. Eight (12.9%) of 62 completely resected patients had a pathologic complete response. Seven patients (7.8%) died during the postoperative period. The median overall survival time was 15.9 months, 3-year survival rate was 36.8%, and 5-year survival rate was 21.1%, with no significant differences in survival between stage IIIA and stage IIIB patients. Median survival time was 48.5 months for 62 completely resected patients, 12.9 months for 13 incompletely resected patients, and 16.8 months for 15 nonresected patients (P = .005). Three- and 5-year survival rates were 60.1% and 41.4% for completely resected patients, 23.1% and 11.5% for incompletely resected patients, and 31.1% and 0% for nonresected patients, respectively. In the multivariate analysis, complete resection (hazard ratio [HR] = 0.35; P  .0001), clinical response (HR = 0.32; P  .0001), and age younger than 60 years (HR = 0.64; P = .027) were the most powerful prognostic factors. Conclusion Induction chemotherapy followed by surgery is effective in stage IIIA and in selected stage IIIB patients attaining complete resection. J Clin Oncol 25:4736-4742. © 2007 by American Society of Clinical Oncology INTRODUCTION Complete resection plays a central role as a cura- tive treatment for locally advanced (stage IIIA N2) non–small-cell lung cancer (NSCLC) after induc- tion chemotherapy with or without preoperative radiotherapy. 1-4 It is also crucial in selected sub- groups of stage IIIB NSCLC patients, 5-7 where the judgment and skill of the surgeon is of the utmost importance. 8 A landmark study of induc- tion chemotherapy in stage IIIA N2 NSCLC re- ported a 65% complete resection rate among 136 patients, with a median survival time of 27 months and 3- and 5-year survival rates of 41% and 26%, respectively, whereas for incompletely resected or nonresectable patients, median sur- vival time was 12 months, and 3- and 5-year sur- vival rates were 5% (P  .001). 9 In a more recent study by the Leuven Lung Cancer Group of 131 stage IIIA N2 patients, the response rate was 54%, the median survival time was 24 months, and 5-year survival rate was 21%. 10 The Cancer and Leukemia Group B 8935 study in stage IIIA N2 patients attained complete resection in 23 pa- tients (36.5% of those undergoing thoracotomy); median survival time in these patients was 20.9 From the Hospital Ramon y Cajal; Hospital San Carlos; Clinica Puerta de Hierro; Fundacion Jimenez Diaz; Auto- nomous University of Madrid, Madrid; Hospital Clinico, Valencia; Hospital Clinico; Hospital Miguel Servet, Zara- goza; Hospital Germans Trias i Pujol, Catalan Institute of Oncology, Badalona; Hospital Duran i Reynals, Catalan Insti- tute of Oncology, Bellvitge; Hospital Cruces, Bilbao; and Hospital General, Alicante, Spain. Submitted April 2, 2007; accepted June 28, 2007. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Address reprint requests to Rafael Rosell, MD, Chief, Medical Oncology Service, Scientific Director of Oncology Research, Catalan Institute of Oncol- ogy, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Badalona (Barcelona), Spain; e-mail: rrosell@ico.scs.es. © 2007 by American Society of Clinical Oncology 0732-183X/07/2530-4736/$20.00 DOI: 10.1200/JCO.2007.12.0014 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 25  NUMBER 30  OCTOBER 20 2007 4736 Downloaded from ascopubs.org by 3.80.95.204 on June 21, 2022 from 003.080.095.204 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.