Exploring PIPAC for Peritoneal Mesothelioma: Can Aerosolized Chemotherapy Expand Treatment Options?

Peritoneal mesothelioma is an uncommon form of mesothelioma that develops in the thin membrane that lines the abdominal cavity. Although it represents a minority of mesothelioma diagnoses, the disease can be particularly challenging to manage because it often remains undetected until it has spread throughout the abdomen.

For patients whose cancer is confined enough to be removed, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) remains the standard treatment with the greatest potential for long-term disease control. Unfortunately, not everyone qualifies for this intensive approach. Extensive tumor spread, underlying medical conditions, or reduced physical fitness may make major surgery too risky or technically impossible.

As a result, researchers continue to investigate alternative therapies for patients with more advanced disease. One approach attracting growing interest is Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC), a technique designed to deliver chemotherapy directly to cancer deposits inside the abdomen.

A Different Way to Deliver Chemotherapy

Unlike traditional intravenous chemotherapy, which travels throughout the bloodstream before reaching tumors, PIPAC administers chemotherapy directly into the abdominal cavity.

The procedure is performed laparoscopically through small incisions. After inserting a camera and specialized instruments, physicians aerosolize chemotherapy drugs into a fine mist and release them into the abdomen under controlled pressure. The pressurized environment is intended to improve drug distribution and encourage deeper penetration into tumor tissue.

Researchers believe this method may address one of the major limitations of conventional chemotherapy. Tumors growing on the peritoneal surfaces can be difficult to reach effectively, even when chemotherapy is delivered into the abdomen as a liquid. By dispersing chemotherapy as an aerosol under pressure, PIPAC may expose a larger surface area of tumor tissue to treatment.

Another potential advantage is that lower doses of chemotherapy can often be used because the medication is concentrated where the cancer is located rather than distributed throughout the entire body. In addition, the procedure can be repeated over time, allowing physicians to evaluate tumor response and adjust treatment plans as needed.

Why Researchers Are Interested in PIPAC

Peritoneal mesothelioma tends to spread across the surfaces of the abdominal cavity rather than forming a single easily removable mass. This growth pattern creates unique treatment challenges.

Many tumors develop increased internal pressure that can limit the ability of chemotherapy drugs to penetrate deeply into cancerous tissue. Researchers theorize that the pressurized delivery used in PIPAC may help overcome some of these barriers and improve drug uptake.

To better understand the therapy’s potential, investigators recently reviewed 13 studies published between 2017 and 2024 involving patients with peritoneal mesothelioma and other cancers affecting the abdominal lining. While the studies varied considerably in design and patient populations, the overall findings suggested that PIPAC may offer meaningful benefits for selected patients.

Safety and Tolerability

One of the most encouraging observations was the procedure’s overall safety profile.

Across the reviewed studies, most patients tolerated treatment reasonably well. The side effects reported most frequently were abdominal discomfort, nausea, and vomiting. Serious complications occurred relatively infrequently, affecting roughly 8% of patients.

Treatment-related deaths were rare, and many patients successfully completed multiple rounds of PIPAC therapy. This is particularly important because repeated treatments may be necessary to achieve meaningful disease control.

Several investigators also reported improvements in symptom management and overall quality of life. For patients living with advanced cancer, maintaining comfort and daily functioning can be just as important as slowing tumor growth.

Evidence of Tumor Response

Although the available research remains preliminary, several studies reported signals that tumors were responding to treatment.

In some cases, tissue samples collected during repeat procedures showed evidence of cancer regression. Other studies reported reductions in tumor burden based on imaging scans or direct surgical assessment.

Because researchers used different methods to evaluate treatment response, comparing results across studies remains difficult. Nevertheless, the overall trend suggested that PIPAC may have meaningful anti-cancer activity in at least a subset of patients.

Could PIPAC Open the Door to Surgery?

Perhaps the most intriguing possibility is PIPAC’s potential role in helping patients eventually qualify for surgery.

Patients with extensive disease are often considered ineligible for CRS-HIPEC because complete tumor removal is unlikely. However, several studies described patients whose disease became sufficiently controlled after PIPAC-based treatment that surgery later became feasible.

One report found that more than half of patients initially considered unresectable ultimately underwent CRS-HIPEC after receiving PIPAC combined with systemic chemotherapy.

Although these results were observed in relatively small patient groups, they raise the possibility that PIPAC could serve as a “conversion” or “bridging” therapy, reducing disease burden enough to make potentially curative surgery an option for some individuals.

What Do We Know About Survival?

Determining the survival impact of PIPAC remains challenging because most studies have involved small numbers of patients and frequently included several different cancer types.

Even so, reported outcomes have been encouraging. Across various studies, median overall survival ranged from approximately 15 months to more than 26 months. Data from an international PIPAC registry showed a median survival of 33.5 months among patients receiving PIPAC-directed treatment.

These figures compare favorably with historical outcomes for advanced peritoneal mesothelioma. However, researchers emphasize that definitive conclusions cannot yet be drawn because randomized clinical trials are still lacking.

The Need for Better Evidence

Despite growing enthusiasm, PIPAC remains an investigational treatment in many settings.

Most published studies have been retrospective analyses or small prospective trials. Larger studies are needed to determine which patients are most likely to benefit, how often treatments should be administered, and how PIPAC should be integrated with surgery, systemic chemotherapy, immunotherapy, and other emerging treatments.

One study that aimed to answer some of these questions was the MESOTIP trial, which compared standard chemotherapy alone with chemotherapy plus PIPAC. Unfortunately, the trial was halted after unexpected serious adverse events occurred in the combination-treatment group. Although the study did not reach completion, researchers may still be able to learn valuable lessons from the data collected before enrollment stopped.

Looking Ahead

PIPAC represents a novel strategy for treating cancers that spread throughout the abdominal cavity, including peritoneal mesothelioma. Early evidence suggests the procedure is generally well tolerated, may reduce tumor burden, and could potentially help some patients become candidates for surgery when they otherwise would not have been.

Many questions remain unanswered, and further research is essential before PIPAC can be considered a standard treatment. Nevertheless, the results seen so far provide reason for cautious optimism. As ongoing studies continue to evaluate this approach, physicians and patients may gain an important new option for managing a disease that has historically been difficult to treat.