PIPAC for Peritoneal Mesothelioma: A Promising Treatment Under Investigation

Malignant peritoneal mesothelioma is a rare cancer that develops in the lining of the abdomen, known as the peritoneum. Although it accounts for only a small percentage of all mesothelioma cases, it can be difficult to diagnose and treat because symptoms often appear only after the disease has advanced.

For some patients, surgery combined with heated chemotherapy delivered directly into the abdomen, a procedure called CRS-HIPEC, offers the best chance for long-term survival. However, many patients are not candidates for this aggressive treatment because their cancer has spread too extensively or because their overall health does not allow them to undergo major surgery.

Researchers are now studying a newer approach called Pressurized Intraperitoneal Aerosol Chemotherapy, or PIPAC, which may help certain patients whose disease cannot be removed surgically.

What Is PIPAC?

PIPAC is a minimally invasive procedure that delivers chemotherapy directly into the abdominal cavity as a pressurized aerosol, or fine mist.

During the procedure, surgeons make small incisions in the abdomen and insert a laparoscope, a thin tube with a camera. Chemotherapy drugs are then sprayed into the abdominal cavity under pressure. The pressure helps the medication spread more evenly and penetrate deeper into tumor tissue than traditional liquid chemotherapy.

Unlike standard intravenous chemotherapy, which circulates throughout the entire body, PIPAC focuses treatment directly where the cancer is located. This approach may allow doctors to use lower doses of chemotherapy while reducing some systemic side effects.

PIPAC can also be repeated multiple times, allowing physicians to monitor how tumors respond between treatments.

Why is PIPAC a Promising Treatment for Peritoneal Mesothelioma?

One of the biggest challenges in treating peritoneal mesothelioma is getting enough chemotherapy into tumors growing throughout the abdominal cavity.

Traditional intraperitoneal chemotherapy sometimes struggles to reach all cancer deposits because tumors can create high internal pressure that blocks drug penetration. Researchers believe PIPAC may overcome some of these limitations by using pressure to help chemotherapy reach more cancer cells.

The recent review examined results from 13 clinical studies conducted between 2017 and 2024. Together, these studies evaluated PIPAC in patients with peritoneal mesothelioma and other cancers that had spread within the abdomen.

Although many of the studies were small, researchers found encouraging signs that PIPAC may help control disease in selected patients.

What Did the Studies Show?

The review found that PIPAC was generally safe and well tolerated.

The most commonly reported side effects included abdominal pain, nausea, and vomiting. Serious complications were relatively uncommon, occurring in approximately 8% of patients across the studies analyzed.

Importantly, researchers reported low rates of treatment-related mortality and found that most patients were able to undergo multiple PIPAC procedures.

Several studies also observed improvements in symptoms and quality of life, an important consideration for patients with advanced disease.

Researchers found evidence that tumors often responded to treatment. In some studies, biopsies showed signs that cancer cells were regressing after repeated PIPAC treatments. Imaging scans and surgical evaluations also demonstrated reductions in tumor burden in certain patients.

While these findings are encouraging, the authors emphasized that response measurements varied between studies, making it difficult to compare results directly.

Could PIPAC Help Patients Become Eligible for Surgery?

One of the most intriguing findings involved patients who initially were not considered candidates for CRS-HIPEC surgery.

Several studies reported that after undergoing PIPAC, some patients experienced enough disease control to later undergo potentially curative surgery.

In one study, more than half of patients with unresectable peritoneal mesothelioma eventually became eligible for CRS-HIPEC following treatment with PIPAC and systemic chemotherapy.

Researchers caution that these findings come from small studies and should be interpreted carefully. However, they suggest that PIPAC could potentially serve as a “bridge” therapy that helps certain patients reach surgery who otherwise would not have qualified.

Survival Data after PIPAC

Because many of the available studies were small and included different types of abdominal cancers, it is difficult to determine exactly how much PIPAC improves survival for patients with peritoneal mesothelioma.

However, several studies reported median overall survival times ranging from approximately 15 months to more than 26 months after treatment. Data from a large international PIPAC registry reported a median survival of 33.5 months among patients receiving PIPAC-directed therapy.

While these numbers appear promising compared with the historically poor prognosis associated with advanced peritoneal mesothelioma, researchers stress that more rigorous studies are needed before firm conclusions can be drawn.

What Comes Next?

The review’s authors conclude that PIPAC shows significant promise but remains an evolving treatment.

Most of the available evidence comes from retrospective studies and relatively small patient populations. Larger, well-designed clinical trials are needed to determine which patients benefit most, how PIPAC should be combined with other treatments, and whether it truly improves survival.

One study mentioned in the manuscript as potentially able to provide some answers was unfortunately suspended. The MESOTIP trial compared standard systemic chemotherapy alone with chemotherapy combined with PIPAC. Although the study did not conclude due to unexpected serious adverse effects in the group undergoing the combination of systemic chemotherapy and PIPAC, we may still be able to gain some insight from the work they were able to achieve.

The Bottom Line

PIPAC represents an innovative approach to delivering chemotherapy directly to tumors in the abdomen. Early research suggests it is generally safe, may help control tumor growth, and could potentially allow some patients with previously unresectable disease to become candidates for surgery.

While many questions remain unanswered, PIPAC offers hope for patients with peritoneal mesothelioma who have limited treatment options. As ongoing clinical trials report results, doctors will gain a clearer understanding of where this emerging therapy fits within the broader treatment landscape for this rare cancer.