PERISCOPE II

Background

Phase 3, European multicentre (8 tertiary hospitals), randomised, controlled trial in 102 patients (51 per group) with resectable cT3/cT4a gastric adenocarcinoma and limited peritoneal metastases (Peritoneal Cancer Index <7) or positive peritoneal cytology, without progression after ≥3 cycles of systemic therapy. Closed early after an unplanned interim futility analysis.

Results

Interventions and follow up: Arm A: Gastrectomy + cytoreductive surgery + HIPEC (oxaliplatin 460 mg/m² at 41°C + docetaxel 50 mg/m² at 37°C)
Arm B: Continuation of systemic therapy alone
Primary endpoint: Overall survival (intention-to-treat)
mFollow up: 67 months
Results: OS: 15.7 months (95% CI 11.4-25.5, experimental) vs 16.6 months (14.1-21.9, standard); HR 1.10 (0.69-1.74); P=.70

Adverse events

Grade ≥3: 42% (experimental) vs 20% (standard)
Serious AEs: 44% vs 6%
Treatment-related deaths: 3, all experimental (ARDS, anastomotic leak, bleeding)

Conclusions

Gastrectomy with cytoreductive surgery and HIPEC provided no overall survival benefit over systemic therapy alone (HR 1.10; P=.70) in gastric cancer with limited peritoneal metastases, while causing substantially more morbidity and treatment-related deaths.

Key Limitations

Stopped early for futility, leaving the trial underpowered (N=102); open-label; a single experimental HIPEC regimen was tested; substantial surgical morbidity and three treatment-related deaths in the experimental arm; heterogeneous systemic therapy backbones.

Clinical Context

This is the first phase 3 comparison of CRS + HIPEC versus systemic therapy in gastric cancer with limited peritoneal disease, and it was negative. It reinforces NCCN and ESMO positioning that CRS/HIPEC for gastric peritoneal metastases remains investigational and should not be offered outside clinical trials; systemic therapy remains the standard of care.

References