Management of Gastric Adenocarcinoma with Peritoneal Carcinomatosis
For gastric cancer with peritoneal carcinomatosis, systemic chemotherapy remains the primary treatment, with cytoreductive surgery plus HIPEC reserved only for highly selected patients with limited peritoneal disease (PCI <7), good performance status (ECOG 0-1), and demonstrated response to neoadjuvant chemotherapy. 1
Initial Assessment and Molecular Testing
Before initiating treatment, obtain the following molecular markers to guide systemic therapy selection:
- HER2 status (IHC/FISH)
- PD-L1 expression (CPS scoring)
- MSI/MMR status (IHC or PCR)
- CLDN18.2 expression (≥75% of tumor cells with 2+ or 3+ membranous staining for zolbetuximab eligibility)
- Consider NGS panel via validated assay 1, 2
Assess performance status using ECOG or Karnofsky scales, as this determines treatment eligibility.
Treatment Algorithm Based on Disease Extent and Patient Factors
For Patients with ECOG ≥3 or KPS <60%
Offer palliative/best supportive care only without systemic therapy 1
For Patients with Good Performance Status (ECOG 0-2, KPS ≥60%)
Primary Approach: Systemic Chemotherapy
Systemic chemotherapy is the standard of care for peritoneal carcinomatosis. Incorporate molecular-targeted agents based on biomarker results:
- HER2-positive: Add trastuzumab to chemotherapy backbone
- PD-L1 CPS ≥1 or MSI-H/dMMR: Consider pembrolizumab
- CLDN18.2-positive: Consider zolbetuximab 1
Selective Surgical Approach: CRS + HIPEC
Patient Selection Criteria (ALL must be met):
- Limited peritoneal disease: PCI <7 1, 3, 4
- Good performance status: ECOG 0-1 4
- Demonstrated response or stable disease after neoadjuvant systemic chemotherapy 1, 2
- No distant metastases (liver, lung, distant nodes) 4
- Medically fit for major surgery
- Complete cytoreduction deemed achievable 1
Critical Evidence Nuances:
The most recent phase III trial (GASTRIPEC-I) showed no significant overall survival benefit when adding HIPEC to cytoreductive surgery (HR 0.72, P=0.1647), though PFS improved modestly (7.1 vs 3.5 months, P=0.0472) 1. This contrasts with earlier smaller phase III data showing survival benefit (11 vs 6.5 months, P=0.046) 1.
The conflicting data reflects that:
- Nearly half of GASTRIPEC-I patients had PCI ≥7 (too extensive)
- Many patients progressed during neoadjuvant therapy and were excluded
- Patient selection is paramount—benefits only seen in those with truly limited disease
The CYTO-CHIP study (277 patients) demonstrated improved OS and recurrence-free survival with HIPEC without increased morbidity, but median PCI remained higher in the HIPEC group, suggesting selection bias 1.
Morbidity Considerations: Phase II data shows 70% 90-day morbidity (though 0% mortality) with median OS of 16.1 months 1. Serious adverse events occur in approximately 15% of patients 1.
For Positive Cytology or Very Low-Volume Disease
Consider conversion strategy with:
- Neoadjuvant systemic chemotherapy followed by reassessment
- Neoadjuvant laparoscopic HIPEC (NLHIPEC) after systemic therapy
- Neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) in bidirectional manner 2, 5
If conversion to negative cytology or resolution of peritoneal metastases occurs, gastrectomy may be considered 2.
What NOT to Do
Avoid palliative gastrectomy without metastasectomy: The REGATTA trial definitively showed that gastrectomy plus chemotherapy for oligometastatic disease does not improve survival compared to chemotherapy alone 6. Surgery should only be performed if complete cytoreduction of all disease is achievable.
Do not use PIPAC outside clinical trials: Pressurized intraperitoneal aerosolized chemotherapy remains investigational 1.
Ongoing Uncertainty
Two phase III trials (RENAISSANCE NCT02578368 and SURGIGAST NCT03042169) are evaluating surgery in oligometastatic disease 6. The Dutch PERISCOPE II trial is specifically examining gastrectomy followed by CRS + HIPEC versus systemic treatment in resectable cT3-T4 gastric cancer with limited peritoneal carcinoma (PCI <7) 1.
Practical Clinical Approach
Most patients with peritoneal carcinomatosis should receive systemic chemotherapy with best supportive care. Only refer highly selected patients (PCI <7, ECOG 0-1, chemotherapy-responsive disease, no distant metastases) to high-volume centers with CRS/HIPEC expertise for multidisciplinary evaluation. The evidence for CRS + HIPEC remains mixed, with the most recent and largest phase III trial (GASTRIPEC-I) failing to show OS benefit, making patient selection absolutely critical 1.