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Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric CancerThe CLASS-01 Randomized Clinical Trial

Educational Objective
To understand the benefits of laparoscopic distal gastrectomy for locally advanced gastric cancer.
1 Credit CME
Key Points

Question  Does laparoscopic distal gastrectomy yield inferior oncological outcomes to open distal gastrectomy for patients with locally advanced gastric cancer?

Findings  In this randomized clinical trial that included 1056 patients with clinically staged locally advanced gastric cancer, laparoscopic vs open distal gastrectomy resulted in a 3-year disease-free survival rate of 76.5% vs 77.8%, respectively, a difference that did not exceed the noninferiority margin of −10%.

Meaning  These findings support the use of laparoscopic gastrectomy for patients assessed as having locally advanced cancer preoperatively.

Abstract

Importance  Laparoscopic distal gastrectomy is accepted as a more effective approach to conventional open distal gastrectomy for early-stage gastric cancer. However, efficacy for locally advanced gastric cancer remains uncertain.

Objective  To compare 3-year disease-free survival for patients with locally advanced gastric cancer after laparoscopic distal gastrectomy or open distal gastrectomy.

Design, Setting, and Patients  The study was a noninferiority, open-label, randomized clinical trial at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 2012 to December 2014. Final follow-up was on December 31, 2017.

Interventions  Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histology to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy.

Main Outcomes and Measures  The primary end point was 3-year disease-free survival with a noninferiority margin of −10% to compare laparoscopic distal gastrectomy with open distal gastrectomy. Secondary end points of 3-year overall survival and recurrence patterns were tested for superiority.

Results  Among 1056 patients, 1039 (98.4%; mean age, 56.2 years; 313 [30.1%] women) had surgery (laparoscopic distal gastrectomy [n=519] vs open distal gastrectomy [n=520]), and 999 (94.6%) completed the study. Three-year disease-free survival rate was 76.5% in the laparoscopic distal gastrectomy group and 77.8% in the open distal gastrectomy group, absolute difference of −1.3% and a 1-sided 97.5% CI of −6.5% to ∞, not crossing the prespecified noninferiority margin. Three-year overall survival rate (laparoscopic distal gastrectomy vs open distal gastrectomy: 83.1% vs 85.2%; adjusted hazard ratio, 1.19; 95% CI, 0.87 to 1.64; P = .28) and cumulative incidence of recurrence over the 3-year period (laparoscopic distal gastrectomy vs open distal gastrectomy: 18.8% vs 16.5%; subhazard ratio, 1.15; 95% CI, 0.86 to 1.54; P = .35) did not significantly differ between laparoscopic distal gastrectomy and open distal gastrectomy groups.

Conclusions and Relevance  Among patients with a preoperative clinical stage indicating locally advanced gastric cancer, laparoscopic distal gastrectomy, compared with open distal gastrectomy, did not result in inferior disease-free survival at 3 years.

Trial Registration  ClinicalTrials.gov Identifier: NCT01609309

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Article Information

Corresponding Authors: Guoxin Li, MD, PhD, FRCS, Department of General Surgery, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou 510-515, China (gzliguoxin@163.com); Jiafu Ji, MD, Key laboratory of Carcinogenesis and Translational Research, Ministry of Education Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China (jijiafu@hsc.pku.edu.cn).

Accepted for Publication: April 24, 2019.

Author Contributions: Drs Li and Ji had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Yu and Huang contributed equally to this work.

Concept and design: Yu, Cao, He, Y. Hu, H. Liu, F. Liu, Z. Li, Chen, Ji, G. Li.

Acquisition, analysis, or interpretation of data: Yu, Huang, Sun, Su, Cao, J-K. Hu, Wang, Suo, Tao, Wei, Ying, W. Hu, Du, Y. Hu, H. Liu, Zheng, P. Li, Xie, Z. Li, Zhao, Yang, C. Liu, H. Li, Chen, Ji, G. Li.

Drafting of the manuscript: Yu, Ying, Y. Hu, H. Liu, F. Liu, Yang, G. Li.

Critical revision of the manuscript for important intellectual content: Yu, Huang, Sun, Su, Cao, J-K. Hu, Wang, Suo, Tao, He, Wei, W. Hu, Du, H. Liu, Zheng, P. Li, Xie, Z. Li, Zhao, C. Liu, H. Li, Chen, Ji, G. Li.

Statistical analysis: Y. Hu, H. Liu, Chen.

Obtained funding: Z. Li, G. Li.

Administrative, technical, or material support: Yu, Huang, Sun, Su, Cao, Wang, Suo, Tao, He, Wei, W. Hu, Y. Hu, Zheng, P. Li, Xie, F. Liu, Z. Li, Zhao, C. Liu, H. Li, Ji.

Supervision: Sun, Cao, Tao, Wei, F. Liu, H. Li, Ji, G. Li.

Conflict of Interest Disclosures: None reported.

Funding/Support: Funding was provided by the Guangdong Provincial Science and Technology Key Project (2012A030400012), the National High Technology R&D Program from the Ministry of Science and Technology of China (201300000087), the National Key Technology R&D Program (2017YFC0108300), the Major Program of Science and Technology Program of Guangzhou (201300000087), National Project of Improvement of Complex Diseases Diagnosis and Treatment from National Development and Reform Commission, the Public Welfare in Health Industry Programfrom the National Health and Family Planning Commission of China (201402015), the Key Clinical Specialty Discipline Construction Program from the National Health and Family Planning Commission of China, and the Program of Global Medical Affairs Department of Johnson & Johnson Medical Ltd (IIS2012-100236).

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group: Guoxin Li. Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China; Changming Huang, Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Yihong Sun, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Jiafu Ji, Xiangqian Su, and Ziyu Li, Key laboratory of Carcinogenesis and Translational Research, Ministry of Education, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China; Hui Cao, Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Jiankun Hu, Department of Gastrointestinal Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Kuan Wang, Department of Gastrointestinal Surgery, the Cancer Hospital of Harbin Medical University, Harbin, China; Jian Suo, Department of Gastrointestinal Surgery, the First Hospital, Jilin University, Changchun, China; Kaixiong Tao, Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Xianli He, Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, China; Hongbo Wei, Department of Gastrointestinal Surgery, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; Mingang Ying, Department of Gastrointestinal Oncological Surgery, Fujian Provincial Cancer Hospital, Fuzhou, China; Weiguo Hu, Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Xiaohui Du. Department of General Surgery, General Hospital of PLA, Beijing, China; Yong Li, Department of General Surgery, Guangdong General Hospital, Guangzhou, China; Xuedong Fang. Department of General Surgery, the Second Hospital, Jilin University, Changchun, China; Zhiwei Jiang, Department of General Surgery, Nanjing General Hospital of Nanjing Military Command, Nanjing, China (now at the Department of General Surgery, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China); Xiang Peng, Department of Gastrointestinal Surgery, the First People’s Hospital of Foshan, Foshan, China; Zhongchen Liu, Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen, China; Jian Xu, Department of General Surgery, Jiaozhou Central Hospital of Qingdao, Qingdao, China; Baolin Wang, Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We thank the Chinese Gastric Cancer Association, the Chinese Society of Laparo-Endoscopic Surgery, and the Chinese Society of Gastrointestinal Surgery for scientific support; the Korean Laparoscopic Gastrointestinal Surgery Study Group, the Japanese Laparoscopic Surgery Study Group, and the Japanese Clinical Oncology Group for their generous help. We thank Yanghee Woo, MD, (City of Hope National Medical Center, Duarte, California) and Wen G. Jiang, PhD (Cardiff University-Peking University Joint Cancer Institute, Cardiff University, Heath Park, UK) for their critical revision of the manuscript without compensation. We thank the American Journal Experts (Durham, North Carolina) and the Bioscience Writers, LLC, Houston, Texas) for editing the manuscript for English language and grammar for which they received compensation.

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