Systemic therapy, gastrectomy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy versus systemic therapy alone for gastric cancer with limited peritoneal metastases (PERISCOPE II): final results of a multicentre, randomised, controlled, phase 3 trial after an unplanned commissioned interim analysis.

backgroundCytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is widely used for patients with gastric cancer and peritoneal metastases. However, the efficacy of this treatment has never been compared with that of systemic therapy. We aimed to investigate the efficacy of gastrectomy with cytoreductive surgery and HIPEC for patients with gastric cancer and limited peritoneal metastases, compared with systemic therapy alone.

methodsIn this European, multicentre, randomised, controlled, phase 3 trial (PERISCOPE II) in eight European tertiary referral hospitals, we recruited adults (aged ≥18 years) with resectable cT3 or cT4a gastric adenocarcinoma who had limited peritoneal metastases (Peritoneal Cancer Index <7) or tumour-positive peritoneal cytology, or both, in the absence of disease progression after three or more cycles of systemic therapy. Participants were randomly allocated (1:1) to the standard group (continuation of systemic therapy) or the experimental group (gastrectomy plus cytoreductive surgery and HIPEC with oxaliplatin [460 mg/m

findingsBetween Nov 6, 2017 and Aug 21, 2024, 102 participants were recruited (51 per group). Median age was 60 years (IQR 51-69); 58 (57%) participants were men, 43 (43%) were women, and 86 (85%) were White. Median follow-up was 67 months (IQR 47-73). Median overall survival in the standard group was 16·6 months (95% CI 14·1-21·9), compared with 15·7 months (11·4-25·5) in the experimental group (hazard ratio 1·10 [95% CI 0·69-1·74]; p=0·70). Ten (20%) of 51 patients in the standard group and 21 (42%) of 50 patients in the experimental group had grade 3 or worse adverse events. The most common grade 3 or worse adverse events were anaemia (four [8%] patients) and elevated liver enzymes (four [8%]) in the experimental group, and nausea (two [4%]), elevated liver enzymes (two [4%]), and electrolyte disturbances (two [4%]) in the standard group. Three (6%) of 51 patients in the standard group and 22 (44%) of 50 patients in the experimental group had serious adverse events. At 100 days after randomisation, three treatment-related deaths had occurred, all in the experimental group and attributed to acute respiratory distress syndrome (one patient), anastomotic leakage (one patient), and bleeding (one patient).

interpretationGastrectomy with cytoreductive surgery and HIPEC provided no survival benefit in patients with gastric cancer and limited peritoneal metastases compared with systemic therapy alone.

fundingThe Dutch Cancer Society, the Netherlands Organisation for Health Research and Development, the Dutch Ministry of Health, Henk Boot, the Bengt Ihre Research Foundation, and the Swedish Cancer Society.