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.

Summary

In PERISCOPE II, 102 patients with limited peritoneal metastases from gastric cancer were randomized to continued systemic therapy versus gastrectomy plus cytoreductive surgery and HIPEC. Overall survival was similar between groups (HR 1.10; p=0.70), while grade ≥3 and serious adverse events, including three treatment-related deaths (one due to acute respiratory distress syndrome), were higher with surgery+HIPEC.

Key Findings

• Overall survival was similar: 16.6 months (standard) vs 15.7 months (CRS+HIPEC); HR 1.10 (95% CI 0.69-1.74); p=0.70.
• Grade ≥3 adverse events: 20% (standard) vs 42% (CRS+HIPEC); serious adverse events: 6% vs 44%.
• Three treatment-related deaths occurred only in the CRS+HIPEC group (acute respiratory distress syndrome, anastomotic leakage, bleeding).

Clinical Implications

For gastric cancer with limited peritoneal metastases or positive cytology after induction systemic therapy, continuation of systemic therapy should remain standard. Routine CRS+HIPEC should be avoided outside clinical trials; careful patient selection and optimization of systemic regimens are prioritized.

Limitations

• Modest sample size (n=102) for a phase 3 trial may limit subgroup analyses
• Specific HIPEC regimen (oxaliplatin-based) may limit generalizability to other protocols

Future Directions

Refine candidate selection using biological and imaging markers, compare alternative intraperitoneal strategies, and optimize perioperative systemic therapy sequencing within trial frameworks.