What is the current standard of care for pseudomyxoma peritonei based on the latest clinical trials?

Current Standard of Care for Pseudomyxoma Peritonei

Complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the established standard of care for pseudomyxoma peritonei, with optimal cytoreduction (residual tumor nodules ≤2.5 mm) being the single most critical determinant of long-term survival. 1, 2, 3

Treatment Algorithm

Initial Assessment and Patient Selection

• Confirm histopathological diagnosis and classify into prognostic categories: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), or intermediate/discordant group 2
• Evaluate extent of disease using peritoneal cancer index (PCI) scoring and cross-sectional imaging to determine resectability 3
• Assess performance status and medical fitness for major cytoreductive surgery, as operative mortality ranges from 1-2.4% with morbidity rates of 19-29% 1, 4, 5
• Refer immediately to specialized centers with substantial CRS+HIPEC experience, as outcomes are operator-dependent and most patients cannot be radically treated at non-specialized institutions 5

Definitive Treatment: CRS + HIPEC

The goal is complete macroscopic cytoreduction (CC-0 or CC-1) followed by HIPEC during the same operative session. 1, 2, 3

Surgical Cytoreduction Technique

• Remove all visible tumor deposits from peritoneal surfaces, omentum, and involved organs 1, 2
• Achieve optimal cytoreduction defined as residual tumor nodules ≤2.5 mm (CC-0: no visible disease; CC-1: nodules <2.5 mm) 1, 2, 3
• Complete cytoreduction is achievable in approximately 85-96% of cases at experienced centers 1, 3, 4

HIPEC Administration

• Closed abdomen technique is the preferred approach based on the largest reported series 1, 2
• Chemotherapy regimen: Mitomycin C combined with cisplatin is the most extensively studied combination 1, 2, 3, 5
• Alternative approach: Early postoperative intraperitoneal chemotherapy (EPIC) using mitomycin C and 5-fluoruracil achieves equivalent long-term outcomes to HIPEC 3

Expected Outcomes and Prognostic Factors

Survival Data

• 5-year overall survival: 68-78% in patients achieving complete cytoreduction 1, 3, 4
• 10-year overall survival: 69% with median overall survival not reached in optimally treated patients 3
• 5-year progression-free survival: 31% with recurrence rates of 32.5% 1, 4

Independent Prognostic Factors (in order of importance)

1. Completeness of cytoreduction (CC-0/CC-1 vs. suboptimal) - most critical factor affecting both overall and progression-free survival 1, 2, 3, 4
2. Histological grade - DPAM has significantly better prognosis than PMCA 1, 2, 3
3. No previous systemic chemotherapy - prior systemic treatment predicts worse outcomes 1, 2
4. Female gender - associated with improved overall survival 3
5. Extent of previous surgery - multiple prior debulking procedures worsen prognosis 4

Critical Pitfalls to Avoid

• Do not administer systemic chemotherapy before definitive CRS+HIPEC, as this independently predicts worse overall and progression-free survival 1, 2
• Do not attempt CRS+HIPEC at non-specialized centers, as the disease is rarely radically treated outside expert institutions and patients should be referred immediately upon diagnosis 5
• Do not proceed with HIPEC if complete cytoreduction cannot be achieved, as suboptimal cytoreduction negates the benefit of intraperitoneal chemotherapy 1, 2, 3
• Do not perform multiple palliative debulking procedures prior to definitive treatment, as extent of previous surgery worsens prognosis 4

Nuances in Treatment Selection

The choice between HIPEC and EPIC is institution-dependent, as both techniques achieve equivalent 10-year overall survival (69%) and disease-free survival (47%) when combined with complete cytoreduction 3. HIPEC is administered intraoperatively during the same anesthetic, while EPIC involves postoperative catheter-based delivery over 5 days 3.

Even patients with aggressive histology (PMCA) and extensive disease (PCI ≥21) achieve acceptable survival when complete cytoreduction is accomplished, though outcomes are inferior to low-grade DPAM 3. This supports aggressive surgical treatment in all histological subtypes when complete cytoreduction is technically feasible 3.