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

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.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Flow of Patient Enrollment and Randomization

aData for number screened for eligibility and reasons for exclusion were not available. bIncludes 26 patients who were lost to follow-up and 2 patients who died within 30 days after the surgery (1 due to respiratory failure as a result of pneumonia and the other due to a cerebrovascular accident). cIncludes 14 patients who were lost to follow-up. dIndicates cases with more than 1 missing lymph node station according to the guidelines of The Japanese Research Society for Gastric Cancer (JRSGC) lymph node grouping.

Figure 2.. Kaplan-Meier Curves of Cumulative Probability of Recurrence or Death for Laparoscopic Distal Gastrectomy vs Open Distal Gastrectomy Within 3 Years After Surgery

For both curves the median follow-up was 38 months (interquartile range, 36-42 months).

Figure 3.. Kaplan-Meier Curves of Cumulative Probability of Recurrence or Death for Laparoscopic Distal Gastrectomy vs Open Distal Gastrectomy Within 3 Years After Surgery by Pathologic Stage

The median follow-up for patients with stage III in the laparoscopic group was 37 months (interquartile range [IQR], 31-41 months) and in the open group, 38 months (IQR, 34-41 months; with stage II in the laparoscopic group, 38 months (IQR, 36-44 months) and in the open group, 39 months (IQR, 37-45 months); and with stage I in the laparoscopic, 39 months (IQR, 37-45 months) and in the open group, 39 months (IQR, 37-45 months).