Segmentectomy Versus Lobectomy in Small-Sized Peripheral Non-Small Cell Lung Cancer (JCOG0802/WJOG4607L): A Multicentre, Randomised, Controlled, Phase 3 Trial

Abstract

Background: Lobectomy is the standard of care for early-stage non-small cell lung cancer (NSCLC). The survival and clinical benefits of segmentectomy have not been investigated in a randomized trial setting. We conducted a randomized controlled noninferiority trial comparing segmentectomy and lobectomy for small-sized peripheral NSCLC. Methods: Patients with clinical stage IA NSCLC (tumor diameter ≤2 cm; consolidation/tumor ratio > 0·5) were randomly assigned to undergo either lobectomy or segmentectomy. The primary endpoint was overall survival (OS). The secondary endpoints included postoperative respiratory function, relapse-free survival (RFS), proportion of local relapse, and adverse events. Findings: Between August 10, 2009 and October 21, 2014, 1106 patients (lobectomy, n = 554; segmentectomy, n = 552) were enrolled. Patient baseline clinicopathological factors were well balanced. At a median follow-up of 7·3 years, the 5-year OS was 94·3% for segmentectomy and 91·1% for lobectomy. Superiority as well as noninferiority in OS were confirmed using a stratified Cox regression model (hazard ratio [HR], 0·663; 95% confidence interval [CI], 0·474–0·927; one-sided P < 0·0001 for noninferiority; P = 0·0082 for superiority). Improved OS was observed consistently across all predefined subgroups in the segmentectomy arm. The significant differences at 1 year in the reduction of median forced expiratory volume in 1 second at 1 year between the two arms was 3·5% ( P < 0·0001), which did not reach the predefined threshold of 10%. The 5-year RFS was 88·0% for segmentectomy and 87·9% for lobectomy (HR, 0·998; 95% CI, 0·753–1·323). The proportions of local relapse were 10·5% and 5·4% for segmentectomy and lobectomy, respectively ( P = 0·0018). Fifty-two (63%) of 83 patients and 27 (47%) of 58 patients died of other diseases after lobectomy and segmentectomy, respectively. Interpretation: This was the first phase 3 trial to demonstrate the benefits of segmentectomy in OS. Segmentectomy should be the standard surgical procedure for patients with small-sized peripheral NSCLC. Trial Registration: University Hospital Medical Information Network–Clinical Trial Registry Number: UMI02317. Funding: Ministry of Health, Labor and Welfare of Japan and the Japan Agency for Medical Research and Development Declaration of Interest: All authors declare no competing interests for this study. Ethical Approval: The study protocol was approved by the JCOG and WJOG Protocol Review Committees and the institutional review boards of all participating hospitals.