Peritoneal Mesothelioma

Peritoneal mesothelioma is the second most common type of mesothelioma, accounting for 15–20% of all cases. It develops in the peritoneum — the serous membrane that lines the abdominal cavity and covers the abdominal organs, including the liver, intestines, and stomach.¹

The peritoneum, like the pleura, consists of two layers: the parietal peritoneum (lining the abdominal wall) and the visceral peritoneum (covering the organs). Approximately 500 new cases of peritoneal mesothelioma are diagnosed annually in the United States. Unlike pleural mesothelioma, peritoneal mesothelioma has a somewhat more balanced sex distribution, with women comprising up to 30–40% of cases.²

Asbestos exposure remains the primary cause, though the mechanism differs from pleural mesothelioma. Asbestos fibers are believed to reach the peritoneum through ingestion (swallowed fibers penetrate the intestinal wall) or through lymphatic translocation from the lungs. The latency period is comparable at 20–50 years.³

The prognosis for peritoneal mesothelioma has improved significantly with the development of cytoreductive surgery combined with heated intraperitoneal chemotherapy (HIPEC). At experienced centers, 5-year survival rates for patients who undergo complete cytoreduction with HIPEC now exceed 50%, making peritoneal mesothelioma the type with the best treatment outcomes.⁴

Peritoneal mesothelioma symptoms are nonspecific and develop gradually, which contributes to frequent misdiagnosis as irritable bowel syndrome, ovarian cancer, appendicitis, or other abdominal conditions. Symptoms often do not appear until the tumor has spread extensively across the peritoneal surfaces.¹

Common symptoms include:

• Abdominal pain — Diffuse, persistent pain that may be dull and aching or sharp and cramping. Pain worsens as the tumor grows and invades the abdominal wall or surrounding organs.²
• Abdominal distension and swelling — The abdomen visibly enlarges due to ascites (fluid accumulation in the peritoneal cavity) and/or tumor bulk. Patients may notice clothes fitting tighter around the waist.²
• Ascites — Fluid accumulation in the peritoneal cavity, present in the majority of patients at diagnosis. Ascites causes a sensation of fullness, pressure, and shortness of breath when severe enough to push against the diaphragm.¹
• Changes in bowel habits — Constipation, diarrhea, or alternating patterns may occur as tumor nodules compress or obstruct the intestines.²
• Nausea and vomiting — Result from tumor involvement of the gastrointestinal tract or partial bowel obstruction.
• Loss of appetite (anorexia) and early satiety — Feeling full after eating small amounts due to ascites and tumor mass compressing the stomach.
• Unexplained weight loss — Despite abdominal distension, patients often lose significant body weight due to cachexia and decreased caloric intake.²
• Fatigue — Profound, persistent exhaustion unrelieved by rest.

Less common symptoms:

• Palpable abdominal mass or nodules
• New-onset hernia (umbilical or inguinal) from increased intra-abdominal pressure
• Fever of unknown origin
• Night sweats
• Bowel obstruction (in advanced cases)
• Thrombocytosis (elevated platelet count) as a paraneoplastic finding

In women, peritoneal mesothelioma is frequently misdiagnosed as ovarian cancer because the symptoms and imaging findings overlap significantly. A history of asbestos exposure — including secondary exposure through a family member's occupation — should prompt specific consideration of mesothelioma.²

Asbestos exposure is the established cause of peritoneal mesothelioma, though the proportion of cases with a documented exposure history is somewhat lower (approximately 50–70%) compared to pleural mesothelioma (~80%).³

Asbestos fibers are believed to reach the peritoneum through two primary pathways:

• Ingestion — Asbestos fibers trapped in the mucus of the upper airways are swallowed and pass through the digestive tract. Fibers can penetrate the intestinal wall and become embedded in the peritoneal tissue.³
• Lymphatic translocation — Inhaled fibers that reach the lungs and pleura can migrate to the peritoneum through the lymphatic system, particularly through diaphragmatic lymphatic channels that connect the pleural and peritoneal cavities.³

Once embedded in the peritoneum, asbestos fibers trigger the same cascade of chronic inflammation, oxidative stress, and genetic damage that causes pleural mesothelioma. Key genetic alterations include loss of BAP1, NF2, and CDKN2A tumor suppressor gene function.⁵

The higher proportion of cases without a clear asbestos exposure history, combined with the more balanced sex distribution, has led researchers to investigate additional risk factors for peritoneal mesothelioma, including germline BAP1 mutations (associated with a hereditary cancer syndrome), prior abdominal radiation, and chronic peritoneal inflammation. However, asbestos exposure remains the dominant and best-characterized cause.⁵

Risk factors for peritoneal mesothelioma include:¹

• Asbestos exposure — Both occupational and environmental exposure. Heavy, prolonged exposure correlates with higher risk, but even brief exposures have been linked to the disease.³
• Secondary (take-home) exposure — A significant proportion of peritoneal mesothelioma cases, particularly in women, result from secondary exposure to fibers carried home on a family member's work clothing.³
• Germline BAP1 mutation — Hereditary mutations in the BAP1 tumor suppressor gene are more frequently identified in peritoneal mesothelioma patients than in pleural mesothelioma patients. BAP1-mutant peritoneal mesothelioma may have a distinct clinical profile with younger age at onset and longer survival.⁵
• Female sex (relative to pleural) — Women comprise a larger proportion of peritoneal mesothelioma cases (30–40%) compared to pleural mesothelioma (20%), possibly reflecting differences in exposure pathways or hormonal factors.²
• Prior abdominal radiation — Radiation therapy to the abdomen has been linked to a small number of peritoneal mesothelioma cases.²

Diagnosing peritoneal mesothelioma is challenging because its symptoms and imaging findings overlap with many common abdominal conditions. The diagnostic pathway includes:²

Imaging

• CT scan of the abdomen and pelvis — The primary imaging modality. CT findings suggestive of peritoneal mesothelioma include peritoneal thickening and nodularity, omental caking (thickening of the omental fat pad), ascites, and soft-tissue masses arising from the peritoneal surfaces. CT is also used to calculate the Peritoneal Cancer Index (PCI) for surgical planning.²
• PET-CT — Identifies metabolically active tumor deposits and helps stage the disease. PET-CT is particularly useful for detecting extraperitoneal spread.²
• MRI — Provides additional detail on the extent of peritoneal disease and mesenteric involvement when surgical resection is planned.²

Biopsy and pathology

• Diagnostic laparoscopy — The preferred biopsy method. Laparoscopy allows direct visualization of the peritoneal surfaces, collection of tissue samples for histological analysis, and assessment of disease extent (PCI scoring). It provides larger and more representative tissue samples than needle biopsy.²
• CT-guided core needle biopsy — A less invasive alternative when accessible tumor deposits are identified on imaging.²
• Paracentesis (ascitic fluid analysis) — While cytological examination of ascitic fluid can suggest mesothelioma, fluid cytology alone is insufficient for definitive diagnosis. Tissue biopsy is required.²

Pathological confirmation uses the same immunohistochemistry panel as pleural mesothelioma (calretinin, WT1, CK5/6 positive; CEA, MOC-31, BerEP4 negative). In women, it is particularly important to differentiate peritoneal mesothelioma from serous ovarian carcinoma, which has a similar clinical presentation. Markers such as PAX8 (positive in ovarian cancer, negative in mesothelioma) and ER/PR (positive in ovarian cancer, typically negative in mesothelioma) help make this distinction.⁵

Peritoneal Cancer Index (PCI)

The PCI scoring system divides the abdomen and pelvis into 13 regions and assigns a lesion size score (0–3) to each region, producing a total score of 0–39. The PCI is the most important predictor of whether complete cytoreduction (removal of all visible tumor) can be achieved with surgery, and it correlates strongly with survival outcomes.⁴

Unlike pleural mesothelioma, there is no formal AJCC TNM staging system for peritoneal mesothelioma. Instead, disease extent is assessed using the Peritoneal Cancer Index (PCI), which is the primary tool for surgical planning and prognostication.⁴

The PCI divides the abdomen into 13 regions (9 abdominal regions and 4 small bowel regions). Each region receives a lesion size score:

• LS 0 — No visible tumor
• LS 1 — Tumor nodules ≤0.5 cm
• LS 2 — Tumor nodules 0.5–5.0 cm
• LS 3 — Tumor nodules >5 cm or confluent disease

Total PCI score ranges from 0 to 39. A lower PCI score indicates less extensive disease and predicts a higher likelihood of achieving complete cytoreduction (CC-0 or CC-1 score) during surgery.⁴

PCI and prognosis:

• PCI ≤10 — Generally favorable prognosis; complete cytoreduction achievable in most patients. 5-year survival rates of 70–80% with CRS/HIPEC at experienced centers.⁴
• PCI 11–20 — Intermediate prognosis; complete cytoreduction may be achievable depending on disease distribution. 5-year survival rates of 40–60%.⁴
• PCI 21–39 — Extensive disease; complete cytoreduction is difficult to achieve. 5-year survival rates below 30%. Systemic chemotherapy may be used to reduce disease burden before attempting surgery (neoadjuvant approach).⁴

The completeness of cytoreduction (CC) score after surgery is the single most important prognostic factor:

• CC-0 — No visible residual disease (best prognosis)
• CC-1 — Residual nodules ≤2.5 mm (comparable to CC-0 with HIPEC)
• CC-2 — Residual nodules 2.5 mm–2.5 cm (significantly reduced survival)
• CC-3 — Residual nodules >2.5 cm (poorest surgical outcome)⁴

The standard of care for peritoneal mesothelioma at experienced centers is cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC). This approach has transformed the prognosis of peritoneal mesothelioma from a uniformly fatal disease to one with meaningful long-term survival.⁴

Cytoreductive surgery (CRS) with HIPEC

This combined procedure involves two phases performed during a single operation:

• Cytoreduction — The surgeon removes all visible tumor from the peritoneal surfaces through a combination of peritonectomy (stripping of the peritoneum), organ resection (removal of involved organs or portions of organs), and omentectomy. The goal is complete cytoreduction (CC-0 or CC-1), as the completeness of tumor removal is the strongest predictor of survival.⁴
• HIPEC — Immediately after cytoreduction, heated chemotherapy (typically cisplatin or mitomycin C at 41–43°C) is circulated through the abdominal cavity for 60–90 minutes. The heat enhances chemotherapy penetration into residual microscopic tumor and increases cytotoxicity. The peritoneal-plasma barrier limits systemic absorption, reducing systemic side effects compared to intravenous chemotherapy.⁴

CRS/HIPEC is a major operation with a perioperative complication rate of 30–50% and mortality of 1–4% at experienced centers. Complications include anastomotic leaks, fistulas, infections, bleeding, and prolonged ileus. Recovery typically requires 2–4 weeks of hospitalization.⁴

Systemic chemotherapy

For patients who are not candidates for CRS/HIPEC, or as neoadjuvant therapy before surgery, systemic chemotherapy with pemetrexed plus cisplatin or carboplatin is the standard regimen, mirroring pleural mesothelioma treatment. Response rates are 25–40%, and chemotherapy can reduce disease burden enough to enable subsequent surgery in selected patients.¹

Immunotherapy

While the CheckMate 743 trial leading to FDA approval of nivolumab plus ipilimumab included primarily pleural mesothelioma patients, retrospective data and ongoing trials suggest immunotherapy has activity in peritoneal mesothelioma as well, particularly in patients with non-epithelioid histology or those who have progressed on chemotherapy.⁶

Emerging approaches

• NIPEC (normothermic intraperitoneal chemotherapy) — Post-operative intraperitoneal chemotherapy delivered at normal body temperature through an abdominal port over multiple treatment cycles.
• PIPAC (pressurized intraperitoneal aerosol chemotherapy) — Chemotherapy delivered as an aerosolized spray during laparoscopy, allowing more uniform drug distribution across the peritoneal surface.⁴

The prognosis for peritoneal mesothelioma has improved dramatically with the adoption of CRS/HIPEC. When complete cytoreduction is achieved at experienced centers, 5-year survival rates of 50–65% are attainable — significantly better than pleural mesothelioma outcomes.⁴

Prognostic factors:

• Completeness of cytoreduction — The most important prognostic factor. CC-0/CC-1 resections are associated with median survival of 50–60+ months, while CC-2/CC-3 resections have median survival of 12–24 months.⁴
• PCI score — Lower PCI scores (≤10) correlate with better outcomes. Patients with PCI >20 have significantly worse prognosis.⁴
• Cell type — Epithelioid histology carries a better prognosis than biphasic or sarcomatoid (though sarcomatoid peritoneal mesothelioma is rare). Well-differentiated papillary mesothelioma of the peritoneum is a distinct subtype with an indolent course and excellent long-term survival.⁵
• Lymph node status — Lymph node involvement is less common in peritoneal mesothelioma than in pleural, but when present it carries a worse prognosis.⁴
• Mitotic rate and Ki-67 index — Higher proliferative activity correlates with more aggressive disease and shorter survival.⁵

For patients who are not candidates for CRS/HIPEC and receive systemic chemotherapy alone, median survival is 12–18 months. Best supportive care without active treatment has a median survival of 6–12 months.¹

Prevention of peritoneal mesothelioma follows the same principles as prevention of all asbestos-related diseases: avoiding asbestos exposure.³

• Occupational safety — Compliance with OSHA asbestos standards, including exposure monitoring, respiratory protection, proper work practices, and decontamination procedures.³
• Prevent secondary exposure — Workers should shower and change at the worksite. Work clothing should never be brought home. This is particularly important for peritoneal mesothelioma prevention, as secondary exposure is a documented risk factor, especially in women.³
• Asbestos abatement — Professional inspection and removal of asbestos-containing materials before building renovation or demolition.³
• Environmental awareness — Avoid disturbing naturally occurring asbestos deposits. Residents near historical asbestos contamination sites should be aware of local exposure risks.

No screening protocol has been validated for early detection of peritoneal mesothelioma in asbestos-exposed populations. Research into serum biomarkers (mesothelin, CA-125, fibulin-3) continues, but none are currently recommended for routine screening.²

Living with peritoneal mesothelioma presents unique challenges related to abdominal symptoms, nutritional status, and the demands of CRS/HIPEC recovery.

• Post-CRS/HIPEC recovery — Recovery from cytoreductive surgery with HIPEC is a major undertaking, typically requiring 2–4 weeks of hospitalization and several months of gradual recovery at home. Patients may experience prolonged ileus (slow return of bowel function), temporary stoma placement, and nutritional challenges. Following the surgical team's postoperative instructions carefully is essential for recovery.
• Nutritional support — Abdominal symptoms (ascites, nausea, early satiety, bowel changes) and the effects of surgery and chemotherapy can severely impair nutritional intake. An oncology-specialized dietitian can develop individualized nutrition plans. Parenteral nutrition (IV feeding) may be necessary temporarily after extensive abdominal surgery.
• Ascites management — Recurrent ascites may require periodic paracentesis (fluid drainage) or placement of a peritoneal catheter for ongoing drainage at home.
• Pain management — Abdominal pain from tumor growth or post-surgical adhesions may require a multimodal approach including medications, nerve blocks, and complementary therapies.
• Psychological support — A rare cancer diagnosis can feel isolating. Online support communities and organizations like the Mesothelioma Applied Research Foundation connect patients with others facing similar diagnoses.
• Seek specialized care — CRS/HIPEC outcomes are strongly volume-dependent; patients should seek treatment at centers that perform at least 10–20 peritoneal mesothelioma procedures annually. Consider a second opinion at a specialized center before making treatment decisions.
• Legal and financial rights — As with all asbestos-related diseases, patients may be eligible for compensation. Filing deadlines apply, so early consultation with a mesothelioma attorney is advisable.