Long-term outcome of a randomized phase III trial exploring the significance of extensive intraoperative peritoneal lavage in addition to standard treatment for ≥ T3 resectable gastric cancer: CCOG 1102.

Abstract

1 Background: Extensive intraoperative peritoneal lavage (EIPL) for gastric cancer reportedly improved survival by physically removing and reducing intraperitoneal-free cancer cells in a small-scale randomized trial (Ann Surg 2009). To confirm this, we conducted a multicenter randomized Phase III trial. Methods: Eligibility criteria: (i) histologically confirmed primary gastric adenocarcinoma, (ii) clinically T3(SS), T4a(SE) or T4b(SI), (iii) clinically M0, and (iv) scheduled for total or distal gastrectomy. Patients were intraoperatively randomized to either the EIPL group or the non-EIPL group after confirming the ≥T3 status and resectability. In the EIPL group, peritoneal lavage was conducted at least 10 times using 1L of saline before the closure of the abdomen. In the non-EIPL group, the lavage was conducted with ≤3L of saline. The primary end-point was disease-free survival (DFS). To detect the difference of 15% in 3-year DFS with a both-sided alpha of 5% and 80% power, the planned sample size was 300 cases. This study was registered as UMIN000005907. Results: Between July 2011 and January 2014, 314 patients were registered from 15 institutions. After excluding the R1/R2 resection cases, 295 patients (145 in the EIPL group and 150 in the non-EIPL group) were analyzed. There were no significant differences between the groups in clinicopathologic characteristics. The median volume of saline for the peritoneal lavage was 10.0 L (10 - 12) for the EIPL group and 3.0 L (1 - 4) for the non-EIPL group. No difference was observed in the incidence of postoperative complications. The 3-year DFS was 63.9% in the EIPL group and 59.7% in the non-EIPL group (p = 0.25, Hazard ratio 0.81 [95% CI 0.57-1.16]). The overall survival rate of the EIPL group and non-EIPL group were 75.0%, 73.7% (3 years), and 62.5%, 57.1% (5 years), respectively (p = 0.65). In the subset analysis, no subgroup with significant difference in survival was identified. Conclusions: Although EIPL for advanced gastric cancer was safe and suggested some efficacy, the primary endpoint designed based on the previous small-scale trial was not met. Clinical trial information: 000005907.