Peritoneal Mesothelioma

A distinct mesothelial malignancy of the abdominal cavity — CRS + HIPEC eligibility, Peritoneal Cancer Index, and systemic therapy for non-surgical patients

Key Points

• Malignant peritoneal mesothelioma (MPeM) is a distinct entity from pleural mesothelioma — it arises from the peritoneal mesothelium and has a different natural history, staging system, and curative surgical pathway.
• CRS + HIPEC (cytoreductive surgery + hyperthermic intraperitoneal chemotherapy) achieves 5-year OS of 40–50% in selected epithelioid patients at high-volume centers — comparable to curative-intent surgery in many solid tumors.
• Patient selection for CRS + HIPEC is driven by Peritoneal Cancer Index (PCI ≤20 is the common threshold), epithelioid histology, ECOG PS 0–1, and absence of distant metastases.
• Completeness of cytoreduction (CC score) is the single strongest predictor of survival after CRS + HIPEC — CC-0 (no visible residual) or CC-1 (<2.5 mm residual) are the only outcomes associated with long-term survival.
• HIPEC is most commonly performed with cisplatin (50 mg/m²) ± doxorubicin at 42°C for 60–90 minutes; some centers use mitomycin C as an alternative.
• Patients not eligible for CRS + HIPEC should receive systemic therapy; pemetrexed + platinum remains the chemotherapy backbone, while nivolumab + ipilimumab is active and may be preferred for non-epithelioid histology.
• Bevacizumab has shown activity in peritoneal mesothelioma and is used in some centers in combination with pemetrexed + cisplatin.

Epidemiology & Distinction from Pleural Mesothelioma

Malignant peritoneal mesothelioma (MPeM) accounts for approximately 15–20% of all mesothelioma cases — roughly 500–700 new diagnoses annually in the United States. Despite arising from the same mesothelial cell lineage as pleural mesothelioma (MPM), MPeM is a clinically, pathologically, and therapeutically distinct entity that should not be managed identically to its pleural counterpart. Key distinctions from pleural mesothelioma: • Disease distribution: MPeM spreads along peritoneal surfaces rather than pleural surfaces; it is usually confined to the abdominal cavity for a prolonged period…

Clinical Presentation & Diagnosis

Peritoneal mesothelioma typically has an indolent early course and is often diagnosed at an advanced stage after months of nonspecific symptoms. Common presenting features: • Abdominal distension and ascites: The most frequent presenting complaint; ascites in MPeM is often loculated and recurs rapidly after drainage. • Diffuse abdominal pain: Vague, crampy, or pressure-like; caused by peritoneal tumor implants and mesenteric involvement. • Early satiety and nausea: Reflecting omental and small bowel mesenteric involvement reducing gastric accommodation. • Abdominal mass: Palpable omental…

CRS + HIPEC — Mechanism and Patient Selection

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the only treatment modality with curative potential in peritoneal mesothelioma. The rationale for CRS + HIPEC integrates two principles: 1. Cytoreductive surgery: Maximally removes all macroscopic peritoneal tumor deposits through a combination of peritoneal stripping (parietal and visceral peritonectomy), visceral resections (bowel, spleen, gallbladder, portions of stomach or rectum as needed), omentectomy, and bilateral pelvic peritonectomy. The goal is to leave no visible residual disease (CC-0)…

CRS + HIPEC vs. Systemic Therapy — Outcomes

The survival advantage of CRS + HIPEC over systemic therapy for selected peritoneal mesothelioma patients is compelling, though derived primarily from retrospective and registry data rather than randomized trials (no RCT has been completed comparing the two strategies). CRS + HIPEC outcomes (high-volume centers, epithelioid, CC-0/CC-1): • Median OS: 40–60 months in most large series • 5-year OS: 40–50% (Sugarbaker Washington Cancer Institute registry; Deraco/Milan; French RENAPE network) • 10-year OS: 25–30% in the most favorable patients • Perioperative mortality: <5% at high-volume…

Perioperative & Post-CRS + HIPEC Management

Management around the time of CRS + HIPEC requires a dedicated multidisciplinary team experienced in major abdominal surgery and intraperitoneal chemotherapy delivery. Pre-operative preparation: • Nutritional optimization: Patients with significant ascites and weight loss often have protein-calorie malnutrition. Pre-operative immunonutrition or enteral feeding for 7–14 days improves postoperative outcomes. Albumin >3 g/dL is a commonly used threshold; lower levels are associated with increased morbidity. • Bowel preparation: Full mechanical and antibiotic bowel prep is standard prior to…

Non-Surgical & Systemic Therapy Management

Approximately 50–60% of MPeM patients are not candidates for CRS + HIPEC at presentation — due to high PCI, sarcomatoid histology, poor performance status, extraperitoneal disease, or absence of a high-volume surgical center. These patients are managed with systemic therapy. First-line systemic therapy options: • Nivolumab + ipilimumab: CheckMate 743 enrolled a small MPeM cohort alongside the larger MPM cohort; pooled data suggest activity in peritoneal disease. Many oncologists now extend this IO doublet to MPeM patients, particularly those with non-epithelioid histology. The FDA approval…