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Laparoscopic vs Open Distal Gastrectomy for Locally Advanced Gastric CancerFive-Year Outcomes From the CLASS-01 Randomized Clinical Trial

Educational Objective To identify whether laparoscopic distal gastrectomy (LDG) yields similar 5-year overall survival to open distal gastrectomy (ODG) for patients with locally advanced gastric cancer.
1 Credit CME
JAMA Surgery
Published Online: October 20, 2021
Original Investigation
Changming Huang, MD1;
Hao Liu, MD2;
Yanfeng Hu, MD2;
Yihong Sun, MD3;
Xiangqian Su, MD4;
Hui Cao, MD5;
Jiankun Hu, MD6;
Kuan Wang, MD7;
Jian Suo, MD8;
Kaixiong Tao, MD9;
Xianli He, MD10;
Hongbo Wei, MD11;
Mingang Ying, MD12;
Weiguo Hu, MD13;
Xiaohui Du, MD14;
Jiang Yu, MD2;
Chaohui Zheng, MD1;
Fenglin Liu, MD3;
Ziyu Li, MD15;
Gang Zhao, MD5;
Jiachen Zhang, MPH16;
Pingyan Chen, PhD17;
Guoxin Li, MD, PhD2;
for the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group
Author Affiliations
  • 1Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
  • 2Department of General Surgery, Guangdong Provincial Key Laboratory of Precision and Minimally Invasive Medicine for GI Cancers, Nanfang Hospital, Southern Medical University, Guangzhou, China
  • 3Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
  • 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Cancer Center Unit 4, Peking University Cancer Hospital, Beijing, China
  • 5Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 6Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
  • 7Department of Gastrointestinal Surgery, the Cancer Hospital of Harbin Medical University, Harbin, China
  • 8Department of Gastrointestinal Surgery, the First Hospital, Jilin University, Changchun, China
  • 9Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 10Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
  • 11Department of Gastrointestinal Surgery, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
  • 12Department of Gastrointestinal Oncological Surgery, Fujian Provincial Cancer Hospital, Fujian Medical University Teaching Hospital, Fuzhou, China
  • 13Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 14Department of General Surgery, General Hospital of PLA, Beijing, China
  • 15Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Ward I of the Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
  • 16Clinical Research Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
  • 17Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China
  • Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Groupfor the
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Key Points

Question  Does laparoscopic distal gastrectomy yield similar 5-year overall survival to open distal gastrectomy for patients with locally advanced gastric cancer?

Findings  In this randomized clinical trial of 1056 patients with clinically staged, locally advanced gastric cancer, laparoscopic distal gastrectomy resulted in a 5-year overall survival rate of 73% vs 76% for open distal gastrectomy, with no statistically significant difference between the 2 groups.

Meaning  The finding provides further evidence for the safety and efficacy of laparoscopic gastrectomy for patients assessed preoperatively as having locally advanced cancer.

Abstract

Importance  It is not clear whether laparoscopic and open distal gastrectomy produce similar outcomes among patients with locally advanced gastric cancer. Data from a multicenter, randomized clinical trial (Chinese Laparoscopic Gastrointestinal Surgical Study [CLASS]–01) showed that laparoscopic distal gastrectomy did not result in inferior disease-free survival at 3 years compared with open distal gastrectomy.

Objective  To report 5-year overall survival data from the CLASS-01 trial of laparoscopic vs open distal gastrectomy among patients with locally advanced gastric cancer.

Design, Setting, and Patients  This was a noninferiority, open-label, randomized clinical trial conducted 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 12, 2012, to December 3, 2014. Final follow-up was on December 31, 2019.

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

Main Outcomes and Measures  The 5-year overall survival rates were updated to compare laparoscopic distal gastrectomy with open distal gastrectomy. All analyses were performed on an intention-to-treat basis. In addition, per-protocol and as-treated analyses were performed for overall survival.

Results  Data from 1039 patients (726 men [69.9%]; mean [SD] age, 56.2 [10.7] years) who received curative therapy were analyzed. At 5 years, the overall survival rates were 72.6% in the laparoscopic distal gastrectomy group and 76.3% in the open distal gastrectomy group (log-rank P = .19; hazard ratio, 1.17; 95% CI, 0.93-1.48; P = .19). After comparison for competing risk events, gastric cancer–related deaths (hazard ratio, 1.14; 95% CI, 0.87-1.49; P = .34) and deaths from other causes (hazard ratio, 1.23; 95% CI, 0.74-2.05; P = .42) did not differ significantly between groups. Overall rates of survival did not differ significantly between groups with each tumor stage.

Conclusions and Relevance  This study found that laparoscopic distal gastrectomy with D2 lymphadenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar 5-year overall survival compared with open distal gastrectomy among patients with locally advanced gastric cancer.

Trial Registration  ClinicalTrials.gov Identifier: NCT01609309

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

See More About

Gastroenterology Gastrointestinal Cancer Gastrointestinal Surgery Minimally Invasive Surgery Oncology Gastric Cancer Surgery Surgical Oncology Gastroenterology and Hepatology
Article Information

Accepted for Publication: August 1, 2021.

Published Online: October 20, 2021. doi:10.1001/jamasurg.2021.5104

Corresponding Author: Guoxin Li, MD, PhD, Department of General Surgery, Guangdong Provincial Key Laboratory of Precision and Minimally Invasive Medicine for GI Cancers, Nanfang Hospital, Southern Medical University, 1838 N Guangzhou Ave, Guangzhou 510-515, China (gzliguoxin@163.com).

Author Contributions: Dr G. Li had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Huang, H. Liu, Y. Hu, Sun, Su, Cao, and J. Hu contributed equally to this work and should be considered co–first authors.

Concept and design: Huang, H. Liu, Y. Hu, Sun, Su, Cao, J. Hu, Suo, Tao, He, Wei, Ying, W. Hu, Du, F. Liu, Z. Li, Zhao, Chen, G. Li.

Acquisition, analysis, or interpretation of data: Huang, H. Liu, Sun, Su, Cao, J. Hu, Wang, Yu, Zheng, Zhao, Zhang, Chen, G. Li.

Drafting of the manuscript: Huang, H. Liu, Wei, W. Hu, Du, Yu, F. Liu, Z. Li, Zhao, G. Li.

Critical revision of the manuscript for important intellectual content: Huang, Y. Hu, Sun, Su, Cao, J. Hu, Wang, Suo, Tao, He, Ying, Zheng, Zhao, Zhang, Chen, G. Li.

Statistical analysis: Huang, H. Liu, J. Hu, Wang, Wei, Yu, Zhang, Chen.

Obtained funding: G. Li.

Administrative, technical, or material support: H. Liu, Y. Hu, Sun, Su, Cao, J. Hu, Wang, Suo, Tao, He, Wei, Ying, W. Hu, Du, Zheng, F. Liu, Z. Li, G. Li.

Supervision: Huang, Y. Hu, Sun, Su, Cao, Wang, G. Li.

Conflict of Interest Disclosures: None reported.

Funding/Support: Funding was provided by Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer (grant 2020B121201004), Guangdong Provincial Major Talents Project (grant 2019JC05Y361), National Natural Science Foundation of China (grant 81872013), the National Project of Improvement of Complex Diseases Diagnosis and Treatment from National Development and Reform Commission, 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 (grant IIS2012-100236).

Role of the Funder/Sponsor: The funding sources 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 collaborators are listed in Supplement 3.

Data Sharing Statement: See Supplement 4.

References
1.
Bray  F , Ferlay  J , Soerjomataram  I , Siegel  RL , Torre  LA , Jemal  A .  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.   CA Cancer J Clin. 2018;68(6):394-424. doi:10.3322/caac.21492PubMedGoogle ScholarCrossref
2.
Kitano  S , Iso  Y , Moriyama  M , Sugimachi  K .  Laparoscopy-assisted Billroth I gastrectomy.   Surg Laparosc Endosc. 1994;4(2):146-148.PubMedGoogle Scholar
3.
Honda  M , Hiki  N , Kinoshita  T ,  et al.  Long-term outcomes of laparoscopic versus open surgery for clinical stage I gastric cancer: the LOC-1 Study.   Ann Surg. 2016;264(2):214-222. doi:10.1097/SLA.0000000000001654 PubMedGoogle ScholarCrossref
4.
Kim  W , Kim  HH , Han  SU ,  et al; Korean Laparo-endoscopic Gastrointestinal Surgery Study (KLASS) Group.  Decreased morbidity of laparoscopic distal gastrectomy compared with open distal gastrectomy for stage I gastric cancer: short-term outcomes from a multicenter randomized controlled trial (KLASS-01).   Ann Surg. 2016;263(1):28-35. doi:10.1097/SLA.0000000000001346 PubMedGoogle ScholarCrossref
5.
Hur  H , Lee  HY , Lee  HJ ,  et al.  Efficacy of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer: the protocol of the KLASS-02 multicenter randomized controlled clinical trial.   BMC Cancer. 2015;15:355. doi:10.1186/s12885-015-1365-z PubMedGoogle ScholarCrossref
6.
Japanese Gastric Cancer Association.  Japanese gastric cancer treatment guidelines 2014 (ver. 4).   Gastric Cancer. 2017;20(1):1-19. doi:10.1007/s10120-016-0622-4 PubMedGoogle ScholarCrossref
7.
Katai  H , Sasako  M , Fukuda  H ,  et al; JCOG Gastric Cancer Surgical Study Group.  Safety and feasibility of laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer: a multicenter phase II trial (JCOG 0703).   Gastric Cancer. 2010;13(4):238-244. doi:10.1007/s10120-010-0565-0PubMedGoogle ScholarCrossref
8.
Katai  H , Mizusawa  J , Katayama  H ,  et al.  Survival outcomes after laparoscopy-assisted distal gastrectomy versus open distal gastrectomy with nodal dissection for clinical stage IA or IB gastric cancer (JCOG0912): a multicentre, non-inferiority, phase 3 randomised controlled trial.   Lancet Gastroenterol Hepatol. 2020;5(2):142-151. doi:10.1016/S2468-1253(19)30332-2 PubMedGoogle ScholarCrossref
9.
Kim  HH , Han  SU , Kim  MC ,  et al; Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS) Group.  Effect of laparoscopic distal gastrectomy vs open distal gastrectomy on long-term survival among patients with stage I gastric cancer: the KLASS-01 randomized clinical trial.   JAMA Oncol. 2019;5(4):506-513. doi:10.1001/jamaoncol.2018.6727 PubMedGoogle ScholarCrossref
10.
Li  G , Hu  Y , Liu  H .  Current status of randomized controlled trials for laparoscopic gastric surgery for gastric cancer in China.   Asian J Endosc Surg. 2015;8(3):263-267. doi:10.1111/ases.12198 PubMedGoogle ScholarCrossref
11.
Yu  J , Huang  C , Sun  Y ,  et al; Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group.  Effect of laparoscopic vs open distal gastrectomy on 3-year disease-free survival in patients with locally advanced gastric cancer: the CLASS-01 randomized clinical trial.   JAMA. 2019;321(20):1983-1992. doi:10.1001/jama.2019.5359 PubMedGoogle ScholarCrossref
12.
Hyung  WJ , Yang  HK , Park  YK ,  et al; Korean Laparoendoscopic Gastrointestinal Surgery Study Group.  Long-term outcomes of laparoscopic distal gastrectomy for locally advanced gastric cancer: the KLASS-02-RCT randomized clinical trial.   J Clin Oncol. 2020;38(28):3304-3313. doi:10.1200/JCO.20.01210 PubMedGoogle ScholarCrossref
13.
Hu  Y , Huang  C , Sun  Y ,  et al.  Morbidity and mortality of laparoscopic versus open D2 distal gastrectomy for advanced gastric cancer: a randomized controlled trial.   J Clin Oncol. 2016;34(12):1350-1357. doi:10.1200/JCO.2015.63.7215 PubMedGoogle ScholarCrossref
14.
Hu  Y , Ying  M , Huang  C ,  et al; Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group.  Oncologic outcomes of laparoscopy-assisted gastrectomy for advanced gastric cancer: a large-scale multicenter retrospective cohort study from China.   Surg Endosc. 2014;28(7):2048-2056. doi:10.1007/s00464-014-3426-9 PubMedGoogle ScholarCrossref
15.
Yu  J , Hu  J , Huang  C ,  et al; Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group.  The impact of age and comorbidity on postoperative complications in patients with advanced gastric cancer after laparoscopic D2 gastrectomy: results from the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) group.   Eur J Surg Oncol. 2013;39(10):1144-1149. doi:10.1016/j.ejso.2013.06.021 PubMedGoogle ScholarCrossref
16.
Beyer  K , Baukloh  AK , Kamphues  C ,  et al.  Laparoscopic versus open gastrectomy for locally advanced gastric cancer: a systematic review and meta-analysis of randomized controlled studies.   World J Surg Oncol. 2019;17(1):68. doi:10.1186/s12957-019-1600-1 PubMedGoogle ScholarCrossref
17.
Lee  HJ , Hyung  WJ , Yang  HK ,  et al; Korean Laparo-endoscopic Gastrointestinal Surgery Study (KLASS) Group.  Short-term outcomes of a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy with D2 lymphadenectomy to open distal gastrectomy for locally advanced gastric cancer (KLASS-02-RCT).   Ann Surg. 2019;270(6):983-991. doi:10.1097/SLA.0000000000003217 PubMedGoogle ScholarCrossref
18.
Inaki  N , Etoh  T , Ohyama  T ,  et al.  A multi-institutional, prospective, phase II feasibility study of laparoscopy-assisted distal gastrectomy with D2 lymph node dissection for locally advanced gastric cancer (JLSSG0901).   World J Surg. 2015;39(11):2734-2741. doi:10.1007/s00268-015-3160-z PubMedGoogle ScholarCrossref
19.
Oba  K , Paoletti  X , Alberts  S ,  et al; GASTRIC group.  Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: a meta-analysis.   J Natl Cancer Inst. 2013;105(21):1600-1607. doi:10.1093/jnci/djt270 PubMedGoogle ScholarCrossref
20.
Shinohara  T , Satoh  S , Kanaya  S ,  et al.  Laparoscopic versus open D2 gastrectomy for advanced gastric cancer: a retrospective cohort study.   Surg Endosc. 2013;27(1):286-294. doi:10.1007/s00464-012-2442-x PubMedGoogle ScholarCrossref
21.
Park  DJ , Han  SU , Hyung  WJ ,  et al; Korean Laparoscopic Gastrointestinal Surgery Study (KLASS) Group.  Long-term outcomes after laparoscopy-assisted gastrectomy for advanced gastric cancer: a large-scale multicenter retrospective study.   Surg Endosc. 2012;26(6):1548-1553. doi:10.1007/s00464-011-2065-7 PubMedGoogle ScholarCrossref
22.
Kim  HH , Han  SU , Kim  MC ,  et al.  Long-term results of laparoscopic gastrectomy for gastric cancer: a large-scale case-control and case-matched Korean multicenter study.   J Clin Oncol. 2014;32(7):627-633. doi:10.1200/JCO.2013.48.8551 PubMedGoogle ScholarCrossref
23.
Kinoshita  T , Uyama  I , Terashima  M ,  et al; LOC-A Study Group.  Long-term outcomes of laparoscopic versus open surgery for clinical stage II/III gastric cancer: a multicenter cohort study in Japan (LOC-A study).   Ann Surg. 2019;269(5):887-894. doi:10.1097/SLA.0000000000002768 PubMedGoogle ScholarCrossref
24.
Hendriksen  BS , Brooks  AJ , Hollenbeak  CS , Taylor  MD , Reed  MF , Soybel  DI .  The impact of minimally invasive gastrectomy on survival in the USA.   J Gastrointest Surg. 2020;24(5):1000-1009. doi:10.1007/s11605-019-04263-4 PubMedGoogle ScholarCrossref
25.
Huang  B , Kuan  PF .  Comparison of the restricted mean survival time with the hazard ratio in superiority trials with a time-to-event end point.   Pharm Stat. 2018;17(3):202-213. doi:10.1002/pst.1846 PubMedGoogle ScholarCrossref
26.
Royston  P , Parmar  MK .  Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event outcome.   BMC Med Res Methodol. 2013;13:152. doi:10.1186/1471-2288-13-152 PubMedGoogle ScholarCrossref
27.
Pak  K , Uno  H , Kim  DH ,  et al.  Interpretability of cancer clinical trial results using restricted mean survival time as an alternative to the hazard ratio.   JAMA Oncol. 2017;3(12):1692-1696. doi:10.1001/jamaoncol.2017.2797 PubMedGoogle ScholarCrossref
28.
Weir  IR , Marshall  GD , Schneider  JI ,  et al.  Interpretation of time-to-event outcomes in randomized trials: an online randomized experiment.   Ann Oncol. 2019;30(1):96-102. doi:10.1093/annonc/mdy462 PubMedGoogle ScholarCrossref
29.
Greenleaf  EK , Sun  SX , Hollenbeak  CS , Wong  J .  Minimally invasive surgery for gastric cancer: the American experience.   Gastric Cancer. 2017;20(2):368-378. doi:10.1007/s10120-016-0605-5 PubMedGoogle ScholarCrossref
30.
Haverkamp  L , Brenkman  HJ , Seesing  MF ,  et al; LOGICA study group.  Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial).   BMC Cancer. 2015;15:556. doi:10.1186/s12885-015-1551-z PubMedGoogle ScholarCrossref
31.
Strong  VE , Song  KY , Park  CH ,  et al.  Comparison of gastric cancer survival following R0 resection in the United States and Korea using an internationally validated nomogram.   Ann Surg. 2010;251(4):640-646. doi:10.1097/SLA.0b013e3181d3d29b PubMedGoogle ScholarCrossref
32.
Strong  VE , Song  KY , Park  CH ,  et al.  Comparison of disease-specific survival in the United States and Korea after resection for early-stage node-negative gastric carcinoma.   J Surg Oncol. 2013;107(6):634-640. doi:10.1002/jso.23288 PubMedGoogle ScholarCrossref
33.
Liu  F , Huang  C , Xu  Z ,  et al; Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group.  Morbidity and mortality of laparoscopic vs open total gastrectomy for clinical stage I gastric cancer: the CLASS02 multicenter randomized clinical trial.   JAMA Oncol. 2020;6(10):1590-1597. doi:10.1001/jamaoncol.2020.3152 PubMedGoogle ScholarCrossref
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