What are the management options for gastric cancer with peritoneal carcinomatosis?

Management of Gastric Cancer with Peritoneal Carcinomatosis

For gastric cancer with peritoneal carcinomatosis, palliative systemic chemotherapy remains the standard approach, but cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) should be offered to highly selected patients with limited disease burden (PCI <6-7) at experienced centers, as this provides significant survival benefit over chemotherapy alone. 1

Patient Stratification and Treatment Algorithm

Performance Status Assessment

• Patients with ECOG PS ≥3 or Karnofsky Performance Status <60%: Offer palliative/best supportive care only 1
• Patients with better performance status: Consider systemic therapy with or without peritoneal-directed treatments based on disease burden 1

Disease Burden Evaluation

• Peritoneal Carcinomatosis Index (PCI) <6-7: Consider CRS + HIPEC after response to systemic chemotherapy 1, 2
• PCI ≥7: Systemic chemotherapy alone or in combination with PIPAC for palliative disease control 2
• Oligometastatic disease with good response to chemotherapy: Conversion gastrectomy may be considered 1

Curative-Intent Approaches (Highly Selected Patients)

Cytoreductive Surgery + HIPEC

This represents the most aggressive curative-intent option and should only be performed at specialized centers with appropriate expertise. 1

Patient Selection Criteria:

• Limited peritoneal disease (PCI <6-7) 1, 2
• Good performance status 3
• Metachronous peritoneal carcinomatosis (better outcomes than synchronous) 1
• No extra-peritoneal unresectable metastases 1
• Ability to achieve complete cytoreduction (R0 resection) 4

Survival Outcomes:

• Median overall survival: 11-24 months (compared to 5-6.5 months with surgery alone) 1, 2
• The CYTO-CHIP phase III trial demonstrated median survival of 11 months with CRS + HIPEC versus 6.5 months with CRS alone (p=0.046) 1
• Recent single-center data shows median survival of 24 months in highly selected patients 2

Risk Profile:

• Major complication rate: 25% (grade 3-4) 2
• Perioperative mortality: 0-7% in recent trials, with experienced centers reporting 0% 4
• PCI >7 is an independent predictor of worse disease-free survival 2

Important Caveat: The GASTRIPEC-I phase III trial showed no significant overall survival benefit with HIPEC addition (HR 0.72, p=0.1647), though progression-free survival improved (7.1 vs 3.5 months, p=0.0472). However, nearly half of patients had PCI ≥7, highlighting the critical importance of patient selection. 1

Conversion Surgery Strategy

For patients achieving excellent response to systemic chemotherapy with near-complete or complete resolution of peritoneal disease, conversion gastrectomy should be considered. 1

Regional Practice Variations:

• Asian guidelines (Korea, China): Recommend conversion gastrectomy after complete resolution of peritoneal metastases with systemic chemotherapy 1
• Western guidelines (US, Europe): Do not require complete resolution; accept limited CRS if complete cytoreduction achievable 1

Palliative Systemic and Intraperitoneal Approaches

Systemic Chemotherapy Alone

This remains the standard for most patients with peritoneal carcinomatosis. 1

• Median overall survival: 5-6 months with chemotherapy alone 2
• Should include molecular testing: HER2, PD-L1, CLDN18.2, MSI/MMR status 1
• Consider next-generation sequencing via validated assay 1

Systemic + Intraperitoneal Chemotherapy (SIPC)

This experimental approach shows promise for conversion to resectable disease in selected patients. 1

Evidence Base:

• Phase II trials demonstrate 71-86% conversion to negative peritoneal cytology 1
• 1-year survival rates >70% 1
• Median overall survival: 21.6-34.6 months after successful conversion gastrectomy 1

PHOENIX-GC Trial Results:

• Primary analysis: No statistical advantage (median OS 18 vs 15 months, p=0.080) 1
• Exploratory analysis adjusting for ascites imbalance: Adjusted HR 0.59, suggesting possible efficacy 1

Current Status: Catheter-based intraperitoneal chemotherapy remains experimental and is primarily used in academic centers in Japan, Singapore, and Korea 1

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

PIPAC represents a novel palliative approach for patients not candidates for CRS + HIPEC. 1

Mechanism: Aerosolized chemotherapy (cisplatin, doxorubicin, or oxaliplatin) delivered laparoscopically directly to peritoneum 1

Evidence:

• Safe and feasible in combination with systemic chemotherapy 1
• Median overall survival: 15 months (better than chemotherapy alone at 5 months, but inferior to CRS + HIPEC at 24 months) 2
• Should only be performed within clinical trials 1

Emerging Combinations: The PIANO study is evaluating PIPAC-delivered oxaliplatin with systemic nivolumab, based on the hypothesis that immunogenic cell death may render immune-cold tumors responsive to checkpoint inhibition 1

Symptom-Directed Palliative Interventions

Gastric Outlet Obstruction

• Palliative gastrojejunostomy: Beneficial for unresectable distal gastric cancer causing obstruction 1
• Endoscopic stenting: Effective alternative, especially for poor performance status patients 1

Reduction Surgery (Palliative Gastrectomy)

This approach remains controversial and is generally NOT recommended based on high-quality evidence. 1

• The REGATTA trial (Asian patients) showed NO survival benefit: 2-year survival 25.1% with gastrectomy + chemotherapy versus 31.7% with chemotherapy alone 1
• May be considered only in highly selected patients with isolated resectable disease and excellent performance status 1

Bleeding and Other Symptoms

• Endoscopic therapies for bleeding control 1
• Angiographic interventions when appropriate 1
• Comprehensive analgesic care 1

Critical Pitfalls to Avoid

1. Overestimating disease burden with CT imaging: CT sensitivity for peritoneal metastases is only 28-51%, despite 97-99% specificity. Diagnostic laparoscopy with peritoneal washings should be strongly considered before initiating treatment. 5

2. Offering CRS + HIPEC to unselected patients: This procedure should be restricted to patients with PCI <6-7, good performance status, and no extra-peritoneal disease at experienced centers only. 1, 2

3. Pursuing reduction surgery based on outdated evidence: The REGATTA trial definitively showed no benefit, and this approach should be abandoned outside of highly exceptional circumstances. 1

4. Performing PIPAC or experimental intraperitoneal chemotherapy outside clinical trials: These approaches lack definitive evidence and should be restricted to research settings. 1

5. Failing to assess molecular markers: HER2, PD-L1, CLDN18.2, and MSI/MMR testing are essential for guiding systemic therapy selection. 1

Geographic Variations in Practice

Asian Practice Patterns:

• More aggressive use of conversion gastrectomy after complete response to chemotherapy 1
• Continued use of catheter-based intraperitoneal chemotherapy in academic centers 1
• Requirement for complete resolution of peritoneal disease before conversion surgery 1

Western Practice Patterns:

• Accept limited residual disease if complete cytoreduction achievable 1
• More restrictive use of intraperitoneal chemotherapy outside HIPEC 1
• Greater emphasis on laparoscopic HIPEC as intermediate step before definitive CRS 1