Pleural mesothelioma is a rare and aggressive cancer that forms in the lining surrounding the lungs. Though there is currently no cure, advances in treatment options—including surgery, chemotherapy, radiation, and immunotherapy—can help extend life and improve quality of life for those diagnosed. Understanding the available therapies and emerging research is essential for patients and their families navigating this challenging disease.

How Treatment Approaches Are Shaping the Fight Against Pleural Mesothelioma

The treatment of pleural mesothelioma aims primarily at controlling symptoms, slowing disease progression, and improving the overall quality of life for patients. Because this cancer typically develops decades after exposure to asbestos—often 25 to 50 years later—it is frequently diagnosed at advanced stages, when tumors have already spread beyond their original site. This makes complete removal of the cancer very difficult. However, medical professionals have developed several approaches to manage the disease, ranging from well-established standard treatments to innovative therapies currently being tested in clinical trials.

Every patient’s treatment plan is unique and depends on multiple factors. These include the stage of the cancer at diagnosis, the specific type of mesothelioma cells involved (such as epithelioid, sarcomatoid, or biphasic), the patient’s overall health and fitness level, and personal preferences. Epithelioid mesothelioma, which accounts for 60 to 80 percent of cases, generally responds better to treatment than the rarer and more aggressive sarcomatoid type. A multidisciplinary team—including medical oncologists, thoracic surgeons, radiation oncologists, and specialist nurses—collaborates to recommend the most appropriate combination of therapies for each individual.^[1][2]

The medical community recognizes that pleural mesothelioma cannot currently be cured, but treatments can potentially extend survival and help patients maintain a better quality of life. Standard treatments approved by medical societies have been in place for years, while ongoing research into new therapies—including drugs tested in clinical trials—offers hope for more effective options in the future.^[3][4]

Standard Treatment Options for Pleural Mesothelioma

For the past two decades, the cornerstone of systemic treatment for pleural mesothelioma has been a combination of chemotherapy drugs. The most widely used regimen involves cisplatin (or sometimes carboplatin) paired with pemetrexed. Cisplatin is a platinum-based drug that works by damaging the DNA inside cancer cells, preventing them from dividing and growing. Pemetrexed, on the other hand, interferes with the building blocks that cancer cells need to replicate. When these two drugs are used together, they have been shown to improve survival compared to using cisplatin alone. Patients receiving this combination typically undergo treatment cycles every 21 days, with each cycle administered on day one.^[12][17]

The response to this chemotherapy regimen varies. In clinical studies, the median survival time for patients treated with cisplatin and pemetrexed was approximately 12 months, compared to about 9 months for those who received cisplatin alone. While this represents a meaningful improvement, it also highlights the limitations of chemotherapy in achieving long-term control of the disease. Common side effects of platinum-based chemotherapy include nausea, vomiting, fatigue, low blood cell counts (which increase the risk of infections and bleeding), kidney problems, and nerve damage. These side effects can significantly impact daily life, and supportive care measures—such as anti-nausea medications and blood transfusions—are often needed.^[17]

Surgery is another important component of standard treatment for pleural mesothelioma, although it is only suitable for a subset of patients. To be considered for surgery, a patient must have early-stage disease that has not spread extensively, and they must be fit enough to tolerate a major operation and recover afterward. The goal of surgery is to remove as much tumor tissue as possible. There are two main surgical approaches. The first, called pleurectomy with decortication, involves removing the pleura (the lining of the lung) and any visible tumor tissue, while preserving the lung itself. This is considered a less aggressive procedure with a lower risk of complications. The second approach, extrapleural pneumonectomy, is more extensive and involves removing the entire lung along with the pleura, part of the diaphragm, and the lining around the heart. Because this surgery is so invasive, it carries a higher risk of complications and is now performed less frequently than in the past.^[11][14]

Surgery alone rarely provides long-term control of mesothelioma, so it is typically combined with other treatments such as chemotherapy or radiation. This is known as multimodal therapy. For example, a patient might undergo surgery to remove the bulk of the tumor, followed by chemotherapy to kill any remaining cancer cells, and then radiation therapy to target specific areas at high risk of recurrence. The theory behind this approach is that attacking the cancer from multiple angles increases the chances of controlling it. However, clinical trials have not consistently shown that surgery combined with other treatments leads to longer survival compared to chemotherapy alone, and the decision to pursue surgery remains controversial among experts.^[14][16]

Radiation therapy uses high-energy beams to destroy cancer cells. In pleural mesothelioma, radiation is most commonly used for palliative purposes—meaning it is intended to relieve symptoms rather than cure the disease. For instance, radiation can help reduce pain caused by tumors pressing on nerves or the chest wall. It may also be used after surgery to target areas where cancer cells might remain. However, delivering effective doses of radiation to the pleura is challenging because of the close proximity of sensitive organs like the lungs, heart, and esophagus. Side effects of radiation can include skin irritation, fatigue, difficulty swallowing, and inflammation of the lungs or esophagus. The duration of radiation treatment varies, but courses typically last several weeks, with treatments given five days per week.^[11][13]

In recent years, immunotherapy has emerged as a powerful tool in the treatment of pleural mesothelioma and has begun to challenge the long-standing dominance of chemotherapy. Immunotherapy works by helping the body’s own immune system recognize and attack cancer cells. Cancer cells often evade the immune system by producing signals that tell immune cells to “stand down.” Immunotherapy drugs can block these inhibitory signals, reactivating the immune response. The combination of two immunotherapy drugs—nivolumab and ipilimumab—was approved by the U.S. Food and Drug Administration in 2020 as a first-line treatment for unresectable (inoperable) pleural mesothelioma. In a large clinical trial, patients who received this immunotherapy combination lived longer on average than those who received standard chemotherapy. The median overall survival was approximately 18 months with immunotherapy compared to 14 months with chemotherapy. Notably, the benefit was particularly pronounced in patients with non-epithelioid histology (sarcomatoid and biphasic types), which are typically harder to treat.^[17][15]

Side effects of immunotherapy are different from those of chemotherapy and result from an overactive immune response. These can include skin rashes, diarrhea, inflammation of the liver or lungs, and problems with hormone-producing glands. In some cases, these immune-related side effects can be severe and require treatment with steroids to suppress the immune system. Despite these potential complications, many patients tolerate immunotherapy well, and for some, the treatment can lead to durable responses that last for years. The approval of immunotherapy has been one of the most significant advances in pleural mesothelioma treatment in the past decade.^[15]

Innovative Therapies Being Tested in Clinical Trials

While standard treatments have improved outcomes for many patients, there remains an urgent need for more effective therapies. This is where clinical trials come in. Clinical trials are research studies that test new drugs, new combinations of existing drugs, or entirely new approaches to treating cancer. They are essential for discovering better treatments and eventually bringing them to patients. For individuals with pleural mesothelioma, participating in a clinical trial may provide access to cutting-edge therapies that are not yet available outside of the research setting.^[12]

One promising area of research involves targeting specific molecules that are commonly altered in mesothelioma cells. Although pleural mesothelioma is primarily characterized by inactivation of tumor suppressor genes rather than activation of oncogenes, scientists have identified several potential therapeutic targets. For example, a protein called mesothelin is highly expressed on the surface of mesothelioma cells but not on most normal cells. This makes it an attractive target for therapies designed to selectively attack cancer cells. Researchers are testing antibody-drug conjugates (ADCs) that consist of an antibody that binds to mesothelin linked to a toxic drug. The idea is that the antibody delivers the toxic payload directly to cancer cells, sparing healthy tissue. Early-phase clinical trials of mesothelin-targeted ADCs have shown some encouraging results, with certain patients experiencing tumor shrinkage. However, more research is needed to determine which patients are most likely to benefit and to optimize dosing schedules.^[18]

Another investigational approach involves exploiting a common genetic alteration in mesothelioma. Many mesothelioma tumors have deletions of a gene called MTAP, which is located next to another important tumor suppressor gene. Loss of MTAP creates a metabolic vulnerability that can potentially be targeted with drugs. Scientists have developed inhibitors that specifically kill cancer cells lacking MTAP while leaving normal cells unharmed—a strategy known as synthetic lethality. These drugs are currently being evaluated in early-phase clinical trials, and initial findings suggest they may have activity against mesothelioma. However, it will take several years of testing to know whether these drugs can improve survival.^[18]

Gene therapy and cell-based therapies represent another frontier in mesothelioma research. Chimeric antigen receptor T-cell (CAR-T) therapy is a form of immunotherapy in which a patient’s own immune cells (T cells) are collected, genetically modified to recognize cancer cells, and then infused back into the patient. CAR-T therapy has achieved remarkable success in treating certain blood cancers, and researchers are now adapting this approach for solid tumors like mesothelioma. In some early trials, CAR-T cells targeting mesothelin have been tested in mesothelioma patients. While the results have been mixed—with some patients experiencing responses and others not—the field is rapidly evolving, and newer generations of CAR-T cells with improved efficacy and safety profiles are under development.^[18]

Clinical trials are conducted in phases. Phase I trials focus primarily on safety, testing a new drug in a small group of patients to determine the appropriate dose and identify side effects. Phase II trials evaluate whether the drug has activity against the cancer, usually in a larger group of patients. Phase III trials compare the new treatment to the current standard of care to see if it offers an advantage in terms of survival or quality of life. Only treatments that successfully pass through all three phases are considered for approval by regulatory agencies. Patients interested in participating in a clinical trial should discuss the options with their medical team. Trials are conducted at specialized cancer centers around the world, including in the United States, Europe, and other regions.^[12]

Some clinical trials are investigating combinations of immunotherapy with other types of treatment. For instance, researchers are testing whether adding chemotherapy to immunotherapy can enhance the immune response and improve outcomes. Other studies are exploring combinations of immunotherapy with drugs that target specific pathways involved in cancer growth, such as inhibitors of proteins that regulate cell division or blood vessel formation. The rationale is that blocking multiple pathways simultaneously may prevent cancer cells from developing resistance to treatment. Preliminary results from some of these combination trials have been promising, but longer follow-up is needed to confirm their benefits.^[15]

Another innovative strategy being explored is hyperthermic intrathoracic chemotherapy (HITHOC). This technique involves delivering heated chemotherapy directly into the chest cavity during or after surgery. The idea is that heat can enhance the ability of chemotherapy to penetrate and kill cancer cells, while limiting exposure to the rest of the body. Some surgeons have reported encouraging results with this approach, particularly when combined with pleurectomy. However, the technique is technically demanding and not widely available, and more research is needed to determine its true benefit.^[14]

Eligibility for clinical trials depends on several factors, including the stage and type of mesothelioma, previous treatments received, overall health, and specific characteristics of the tumor. Some trials require patients to have measurable disease (tumors that can be seen on imaging scans), while others are open to patients who have already received multiple lines of treatment. Information about ongoing clinical trials can be found through resources such as clinicaltrials.gov, cancer center websites, and patient advocacy organizations. Many trials offer support for travel and accommodation for patients who need to travel to participate.^[12]

Most Common Treatment Methods

• Chemotherapy
  • Combination of cisplatin (or carboplatin) and pemetrexed is the most common regimen
  • Administered intravenously every 21 days
  • Works by damaging cancer cell DNA and blocking cell replication
  • Can improve survival by several months compared to no treatment
  • Side effects include nausea, fatigue, low blood counts, and nerve damage
• Immunotherapy
  • Combination of nivolumab and ipilimumab approved as first-line treatment
  • Works by blocking immune checkpoint proteins (PD-1 and CTLA-4) to reactivate immune response against cancer
  • Particularly effective in non-epithelioid mesothelioma subtypes
  • Can lead to durable responses lasting years in some patients
  • Side effects include immune-related inflammation of various organs
• Surgery
  • Pleurectomy with decortication removes the pleura and visible tumor while preserving the lung
  • Extrapleural pneumonectomy removes the entire lung, pleura, and surrounding tissues
  • Only suitable for early-stage disease in fit patients
  • Typically combined with chemotherapy or radiation in multimodal approach
  • Recovery can take several weeks to months
• Radiation Therapy
  • Uses high-energy beams to destroy cancer cells
  • Most commonly used for palliative purposes to relieve pain
  • May be given after surgery to target remaining cancer cells
  • Treatment courses typically last several weeks
  • Side effects include skin irritation, fatigue, and inflammation of nearby organs
• Targeted Therapy (Clinical Trials)
  • Antibody-drug conjugates targeting mesothelin deliver toxic drugs directly to cancer cells
  • MTAP inhibitors exploit metabolic vulnerabilities in mesothelioma cells
  • Being tested in Phase I and II clinical trials
  • Preliminary results show tumor shrinkage in some patients
• Cell-Based Therapy (Clinical Trials)
  • CAR-T cell therapy involves genetically modifying patient’s immune cells to attack cancer
  • Targets proteins like mesothelin expressed on mesothelioma cells
  • Currently in early-phase clinical trials
  • Some patients have experienced responses, but efficacy varies