Laparoscopic versus open distal gastrectomy for clinical T4a gastric cancer: Short-term outcomes and interim survival analysis of the UMC-UPPERGI-01 randomized clinical trial.

Abstract

e16142 Background: Laparoscopic distal gastrectomy (LDG) is widely accepted for early and advanced stages gastric cancer (GC), but its oncological efficacy for T4a tumors remains controversial. We previously demonstrated the surgical safety of LDG with comparable short-term outcomes to open surgery in cT4a GC (JAMA Surgery, 2025). This interim analysis aims to evaluate the oncological outcomes of LDG versus open distal gastrectomy (ODG) in this high-risk population. Methods: In this phase III, single-center, non-inferiority RCT (NCT04384757), patients with cT4aN0-3M0 GC were randomized 1:1 to LDG or ODG with D2 lymphadenectomy. The primary endpoint is 3-year disease-free survival (DFS) with a non-inferiority margin of 1.45 for the Hazard Ratio (HR). Survival rates were estimated using the Kaplan-Meier method, and HRs were calculated using Cox proportional hazards models. All procedures were performed exclusively by qualified surgeons. Results: After exclusion, a total of 208 patients (LDG: 104; ODG: 104) were analyzed. Baseline, pathological characteristics and adjuvant chemotherapy rates were well-balanced . Regarding short-term outcomes, although LDG had longer operative time (220.0 vs 153.7 min; P < 0.001) and higher median blood loss (80 vs 50 mL; p = 0.003), there were no significant differences in 30-day morbidity (22.1% LDG vs 21.2% ODG; p = 0.87) or severe complications (2.9% vs 3.8%; p > 0.99). Recovery parameters including time to first flatus, oral tolerance, and length of hospital stay were also comparable. Moreover, the time from surgery to initiation of adjuvant chemotherapy did not differ between groups. At the interim survival analysis, the 3-year DFS rate was 67% (95% CI, 57%–79%) in the LDG group and 70% (95% CI, 62%–80%) in the ODG group. The estimated HR for DFS was 1.35 (95% CI, 0.78–2.32; p = 0.26). Although the HR point estimate was within the margin, non-inferiority could not be formally established at this stage as the upper limit of the 95% CI (2.32) exceeded the margin (Delta_0 = 1.45). The 3-year overall survival (OS) rate was 76% (95% CI, 66%–86%) in the LDG group and 74% (95% CI, 64%–86%) in the ODG group (HR 1.16; 95% CI, 0.64; 2.11; p = 0.63). Recurrence patterns did not differ significantly between groups. Subgroup analyses (age, tumor size, macroscopic type) showed no significant differences in DFS between the two approaches. Conclusions: This interim analysis of the UMC-UPPERGI-01 trial suggests that LDG provides comparable 3-year survival outcomes to ODG for cT4a gastric cancer. While the statistical non-inferiority is not yet established due to the current interval of follow-up and event accrual, the oncological trends and equivalent recurrence patterns support LDG as a viable surgical alternative in experienced surgeons. Final analysis will provide definitive evidence. Clinical trial information: NCT04384757 .