Treatment Strategy: CRS, HIPEC, and Immunotherapy

The treatment landscape for Malignant Peritoneal Mesothelioma (MPM) has evolved significantly. Decisions are no longer “one-size-fits-all” but are instead guided by your specific tumor “flavor” (histology) and the amount of cancer present (PCI score). The following strategies are based on the Chicago Consensus guidelines, the current international standard for MPM care ^[1].

Note: This information is for educational purposes and does not constitute medical advice.

The Gold Standard: CRS and HIPEC

For eligible patients, the most effective treatment is a two-step procedure designed to remove all visible cancer and then treat invisible cells with heated chemotherapy ^[1].

1. Cytoreductive Surgery (CRS): The surgeon removes all visible tumor nodules from the abdominal lining and organs. The goal is a Completeness of Cytoreduction (CC) score of 0 (no visible disease remaining) or 1 (remaining nodules are less than 2.5 mm) ^[1].
2. Hyperthermic Intraperitoneal Chemotherapy (HIPEC): While you are still in the operating room, a heated chemotherapy solution is circulated throughout your abdomen for 60 to 90 minutes ^[1].

Why must nodules be less than 2.5 mm (CC-1)? The heated chemotherapy wash used in HIPEC can only penetrate tissue up to a depth of about 2 to 3 millimeters. If the remaining tumor nodules are larger than this, the chemotherapy will not reach the cancer cells inside, making the treatment much less effective ^[1].

Who is a candidate?

• Histology: Typically patients with the epithelioid subtype or favorable biphasic cases ^[1].
• Disease Volume: Generally, a PCI score less than 20–25 is preferred to ensure the surgeon can safely remove all the cancer ^[1].

The Rise of Immunotherapy

For many years, traditional chemotherapy (like Cisplatin and Pemetrexed) was the only alternative to surgery. However, immunotherapy has now emerged as a powerful tool, particularly for aggressive cases [NCT05001880].

• Ipilimumab and Nivolumab: These “checkpoint inhibitors” train your immune system to recognize and attack mesothelioma cells. They are now frequently used as the first-line treatment for:
  • Sarcomatoid or high-grade biphasic subtypes, which often respond poorly to surgery ^[1].
  • Unresectable disease, where the cancer has spread too widely (high PCI) for safe surgical removal ^[1].

Understanding the Risks and Side Effects

While these treatments can be life-saving, they are highly aggressive and come with significant risks that must be carefully considered.

• Surgical Morbidity (CRS + HIPEC): This is a major operation that typically requires a stay in the Intensive Care Unit (ICU). Risks include anastomotic leaks (where reconnected parts of the bowel fail to heal and leak fluid into the abdomen), severe infections, internal bleeding, and toxicity from the heated chemotherapy ^[1]. Digestion issues can last for months.
• Immunotherapy Toxicity: Drugs like Ipilimumab and Nivolumab can cause immune-related adverse events (irAEs). Because they ramp up the immune system, the body can mistakenly attack its own healthy organs, leading to inflammation in the lungs (pneumonitis), colon (colitis), liver (hepatitis), or hormone glands [NCT05001880]. These require prompt medical management.

Treatment Decision Pathway

Your team will likely use a pathway similar to this to guide your care: