What are the most promising supportive treatments to add to standard cytoreductive surgery (with or without hyperthermic intraperitoneal chemotherapy) for an adult with peritoneal carcinomatosis?

Most Promising Supportive Treatments for Peritoneal Carcinomatosis

For carefully selected patients with limited peritoneal carcinomatosis (PCI ≤10) and potential for complete cytoreduction, hyperthermic intraperitoneal chemotherapy (HIPEC) added to cytoreductive surgery represents the most promising supportive treatment, improving median survival from 6.5 to 11 months without increasing mortality. 1

Patient Selection Criteria for HIPEC

The success of HIPEC depends critically on strict patient selection:

• Low peritoneal cancer index (PCI ≤10) is essential, as patients with PCI >10 should receive systemic therapy or best supportive care instead 1, 2
• Potential for complete cytoreduction must be established, as incomplete cytoreduction negates survival advantages 1, 2, 3
• No extraperitoneal metastases should be present 1, 4
• Good performance status (ECOG PS <3 or KPS ≥60%) is required 1
• Minimum 3 months of systemic therapy with improved or stable disease on re-staging 1

Evidence Supporting HIPEC

The most compelling recent evidence comes from multiple sources:

• CYTO-CHIP study (277 patients): HIPEC added to cytoreductive surgery improved overall survival and recurrence-free survival without increasing morbidity or mortality in gastric cancer patients 1, 2, 3
• Phase III trial (68 patients): Median survival improved from 6.5 months (surgery alone) to 11 months (surgery plus HIPEC), with similar serious adverse event rates (11.7% vs 14.7%) 1
• GASTRIPEC-I trial: While overall survival showed no significant difference (HR 0.72, P=0.1647), progression-free survival improved significantly (7.1 vs 3.5 months, P=0.0472) 1, 3

Important caveat: The GASTRIPEC-I trial was underpowered due to early closure from poor recruitment, and nearly half of patients had PCI ≥7, highlighting the critical importance of patient selection 1

Safety Profile

HIPEC has an acceptable safety profile when performed at experienced centers:

• Perioperative mortality: 0% in recent high-quality studies, though ranges 0-7% across all trials 2, 3
• Major complications: 9-40% within 30 days, varying by center experience 2, 3
• No increase in serious adverse events compared to cytoreductive surgery alone (14.7% vs 11.7%) 1
• Procedure duration: 300-600 minutes, requiring experienced centers 2

Alternative Intraperitoneal Approaches

For patients who cannot undergo HIPEC, catheter-based intraperitoneal chemotherapy presents a less invasive option:

• Peritoneal port implantation allows repeated IP administration of chemotherapy (commonly taxane-based) with high peritoneal concentrations 1
• Early postoperative intraperitoneal chemotherapy (EPIC) showed reduced PM recurrence rates but significantly higher postoperative complications including intra-abdominal bleeding and sepsis 1
• INPACT trial: Adjuvant IP paclitaxel after gastrectomy did not confer survival or PM-recurrence benefit over IV paclitaxel 1

These catheter-based approaches currently lack strong evidence and should be considered only in clinical trial settings. 1

Molecular Testing and Targeted Therapy

Before initiating any treatment, comprehensive molecular profiling is essential:

• HER2, PD-L1, CLDN18.2, and MSI/MMR testing should be performed 1
• CLDN18.2-positive tumors (≥75% of viable tumor cells with 2+ or 3+ staining) may benefit from zolbetuximab 1
• High tumor mutational burden (TMB-H ≥10 mut/Mb) or MSI-H/dMMR may predict response to checkpoint inhibitors 4
• Next-generation sequencing (NGS) should be considered via validated assay 1

Treatment Algorithm

For patients with peritoneal carcinomatosis as only disease:

1. Initial systemic therapy for minimum 3 months 1
2. Re-staging to assess response 1
3. If PCI ≤10, stable/improved disease, no extraperitoneal disease:
   • Multidisciplinary discussion for cytoreduction candidacy 1
   • If complete cytoreduction predicted: gastrectomy with cytoreductive surgery + HIPEC 1, 3
   • If incomplete cytoreduction predicted: continue systemic therapy or clinical trial 1
4. If PCI >10, disease progression, or extraperitoneal disease:
   • Systemic therapy, clinical trial, or best supportive care 1

Critical Pitfalls to Avoid

• Do not offer HIPEC to patients with high PCI (>10), as outcomes do not justify the procedural burden 1, 2
• Do not proceed if complete cytoreduction is not achievable, as incomplete cytoreduction eliminates survival benefit while maintaining full surgical risk 1, 2, 3
• Do not perform HIPEC at low-volume centers, as institutional experience directly correlates with outcomes and complication rates 2, 3
• Do not use prophylactic HIPEC outside clinical trials, as evidence for prevention of metachronous PM remains unclear 1

Palliative and Supportive Care Integration

For patients not candidates for cytoreductive surgery with HIPEC:

• Symptom-directed best supportive care should be incorporated into all management strategies 1
• Performance status determines treatment intensity: patients with KPS <60% or ECOG PS ≥3 should receive palliative/best supportive care only 1
• Systemic chemotherapy remains the standard for unresectable disease, with modern regimens improving outcomes even in palliative settings 5