Long-term outcomes of laparoscopic distal gastrectomy for locally advanced gastric cancer: An individual patient data meta-analysis of KLASS-02 and CLASS-01 randomized controlled trials

Objective: Laparoscopic distal gastrectomy (LDG) has potential as a surgical treatment option for locally advanced gastric cancer (LAGC). However, there is uncertainty regarding the generalizability of LDG efficacy across diverse patient populations and treatment settings. This study aimed to assess the outcomes of LDG vs. open distal gastrectomy (ODG) in patients with LAGC despite differences in clinical trial populations and treatment environments. Methods: The KLASS-02 and CLASS-01 trials are multicenter, non-inferiority, open-label, randomized controlled trials for patients with LAGC eligible for distal subtotal gastrectomy in Korea and China, respectively. Some 1,050 patients were enrolled in KLASS-02, and 1,056 patients were enrolled in CLASS-01. Individual patient data (IPD) from KLASS-02 and CLASS-01 were pooled and analyzed. Results: There were 900 patients in the LDG group and 920 in the ODG group. Baseline characteristics were well balanced between groups. The LDG group had better short-term and recovery outcomes than the ODG group, although anastomotic leakage was more frequent. For patients who underwent LDG vs. ODG, 5-year overall survival (OS) was 82.7% [95% confidence interval (95% CI), 80.2%−85.2%] vs. 83.3% (95% CI, 80.9%−85.8%) (P=0.706) and 5-year recurrence-free survival (RFS) was 76.9% (95% CI, 74.1%−79.7%) vs. 77.9% (95% CI, 75.2%−80.6%) (P=0.666), respectively, with a median follow-up of 70 months. In the multivariable prognostic IPD meta-analysis, the operative approach was not independently associated with OS [hazard ratio (HR)=1.045, 95% CI, 0.833−1.311; P=0.706] or RFS (HR=1.044, 95% CI, 0.859−1.269; P=0.667) for LDG vs. ODG. In the subgroup analysis, LDG demonstrated a significant association with poorer RFS in the pT4 subgroup (HR=1.377, 95% CI, 1.022−1.760; P=0.034). Conclusions: Despite differences in patient populations, surgical practices, and postoperative treatments between trials, LDG is oncologically safe with the benefit of being minimally invasive for patients with LAGC, except for the pT4 patients. Therefore, LDG could be a good treatment alternative for patients with LAGC; however, caution should be warranted in its application for patients classified as T4.