Pleural Mesothelioma: Symptoms, Diagnosis, Treatment and Prognosis

Pleural Mesothelioma at a Glance

What Is Pleural Mesothelioma?

The pleura is made up of two thin layers of tissue. The visceral pleura covers the lungs, and the parietal pleura lines the inside of the chest wall. A small amount of fluid between these layers helps them move smoothly as you breathe.

Pleural mesothelioma starts when cells in this lining become cancerous. Unlike most lung cancers, it does not start inside the lung. Instead, it usually spreads along the pleura and can eventually affect nearby areas like the chest wall, diaphragm, mediastinum, or pericardium.

Because of these differences, pleural mesothelioma is not the same as lung cancer. They have different biology, staging, and treatment approaches.

The term diffuse pleural mesothelioma is often used in modern pathology and staging literature because the cancer commonly grows across broad areas of the pleura rather than forming one clearly defined mass.

How Common Is Pleural Mesothelioma?

Mesothelioma is rare compared with cancers such as lung, breast, prostate or colorectal cancer. Pleural mesothelioma accounts for the large majority of mesothelioma diagnoses.

Because pleural mesothelioma is rare, diagnosis and treatment may benefit from clinicians and centers with specific experience managing the disease.

This is why getting a second opinion from a center that specializes in pleural mesothelioma can be helpful, especially when making big treatment decisions like surgery or systemic therapy.

What Causes Pleural Mesothelioma?

Asbestos exposure

Asbestos exposure is the major established risk factor for pleural mesothelioma.

Asbestos is a group of naturally occurring mineral fibers that were widely used in insulation, construction materials, shipbuilding, and many industrial products because of their resistance to heat and fire.

When materials with asbestos are disturbed, tiny fibers can get into the air and be breathed in. Some inhaled asbestos fibers can remain in the body for many years and contribute to biological changes associated with the development of mesothelioma.

Mesothelioma often appears decades after the original exposure.

Workplace exposure has been a major risk, especially in jobs where people handled asbestos materials. Exposure can also happen outside of work, such as from the environment or from asbestos fibers brought home on clothing in the past.

Not everyone who is exposed to asbestos will get mesothelioma, and some people with the disease do not recall any specific exposure. Our asbestos exposure guide covers this topic in more detail.

Does smoking cause mesothelioma?

Smoking is not considered an established cause of pleural mesothelioma.

However, smoking is a major cause of lung cancer. People who have been exposed to asbestos and also smoke have a much higher risk of getting lung cancer, which is different from mesothelioma.

Other risk factors

Researchers have studied additional factors that might contribute to mesothelioma in a minority of cases.

Inherited changes involving the BAP1 gene can predispose some families to mesothelioma and several other tumors. Therapeutic radiation and certain unusual mineral exposures have also been investigated.

These rare situations do not change the main fact: asbestos is still the main known environmental cause of pleural mesothelioma.

Symptoms of Pleural Mesothelioma

Symptoms usually appear slowly and are not unique to mesothelioma. They can be caused by the tumor, inflammation of the pleura, or fluid building up around the lung.

Common presentations include shortness of breath, persistent chest discomfort or pain, pleural effusion, persistent cough, fatigue, reduced appetite, and unintended weight loss.

Some people initially notice only increasing breathlessness. Others are evaluated after imaging performed for another reason shows pleural fluid or abnormal pleural thickening.

These symptoms are much more often caused by other conditions, not mesothelioma. Having these symptoms does not mean you have mesothelioma.

If you have ongoing or unexplained breathing problems, you should see a healthcare professional, especially if you have a history of asbestos exposure. Our symptoms guide covers the broader range of possible signs across all mesothelioma types.

How Pleural Mesothelioma Is Diagnosed

Diagnosing pleural mesothelioma usually takes several steps, not just one test. Our diagnosis guide covers this process in more detail.

Medical history and examination

The evaluation typically begins with symptoms, general medical history, and possible occupational or environmental asbestos exposure.

An exposure history can support clinical suspicion, but the absence of a known asbestos exposure does not exclude mesothelioma.

Imaging

A chest X-ray may reveal pleural fluid or other abnormalities, but computed tomography (CT) generally provides much more detail.

CT can help identify pleural thickening, nodularity, pleural effusion, and involvement of nearby structures. It is also important for clinical staging.

PET/CT may be useful in selected patients when clinicians are assessing disease extent or looking for possible metastatic disease. MRI can provide additional information in certain situations, particularly when detailed evaluation of invasion into nearby structures is needed. Our imaging tests guide covers CT, PET, and MRI in more detail.

Imaging tests can make doctors more or less suspicious of mesothelioma, but these tests alone usually cannot confirm the diagnosis.

Pleural fluid testing

Many patients develop a pleural effusion, which is an abnormal collection of fluid between the pleural layers.

Thoracentesis can remove some of this fluid. The procedure can help relieve breathlessness and provides fluid that can be examined for malignant cells.

However, testing pleural fluid has important limits for diagnosing mesothelioma. A negative result does not rule out the disease, and the test may not give enough information to plan treatment.

Biopsy

When planning treatment, it is usually important to get enough tissue for testing.

Depending on the clinical situation, tissue may be obtained through thoracoscopy or an image-guided pleural biopsy.

Thoracoscopy lets doctors look inside the pleural cavity and take several tissue samples. The type of biopsy depends on imaging results, the patient’s health, risks of the procedure, and the planned treatment. Our tests and biopsy guide covers these procedures in more detail.

How pathologists confirm pleural mesothelioma

Diagnosing mesothelioma can be hard because other cancers can spread to the pleura and look similar under the microscope.

A pathologist evaluates the tissue architecture and uses a panel of immunohistochemical markers to distinguish mesothelioma from metastatic carcinoma and other tumors.

No single conventional immunohistochemical marker is sufficient in every case.

Modern pathology may also use tests involving BAP1, MTAP and CDKN2A when distinguishing malignant mesothelioma from benign mesothelial proliferations is difficult. For example, loss of BAP1 or MTAP expression or homozygous deletion of CDKN2A can provide evidence supporting malignancy in the appropriate pathological setting.

Doctors must look at these test results as part of the whole pathology review, not use them alone to diagnose cancer.

Because diagnosing mesothelioma can be tricky, having an expert in thoracic pathology review the case is especially helpful when the diagnosis or type is unclear.

Genetic counseling and germline testing

The 2025 ASCO guideline recommends offering germline genetic testing to all patients with mesothelioma. Testing looks for inherited pathogenic variants that can contribute to cancer susceptibility, including changes involving BAP1 and other cancer-risk genes.

A positive result does not mean that asbestos exposure was unimportant, and it does not by itself determine treatment. However, it may provide information relevant to prognosis, additional cancer surveillance and the potential cancer risk of biological relatives. Genetic testing should ideally be accompanied by counseling from a qualified professional so patients understand the medical and potential family implications of the results.

Histologic Types of Pleural Mesothelioma

Pleural mesothelioma is divided into three major histologic categories.

The type of mesothelioma seen under the microscope (histology) is important because it can affect prognosis and treatment choices.

However, histology is just one factor. Stage, lymph node involvement, overall health, treatment options, and tumor biology also affect outcomes.

Pleural Mesothelioma Staging: AJCC/IASLC Version 9

Pleural mesothelioma is currently staged using the TNM Version 9 system developed from the International Association for the Study of Lung Cancer staging project and incorporated into modern AJCC staging.

TNM describes three different aspects of the disease.

T describes the extent of the primary pleural tumor.
N describes involvement of regional lymph nodes.
M describes distant metastatic spread.

Version 9 introduced important changes to clinical assessment of the primary tumor. In addition to invasion of surrounding structures, radiologic measurements of pleural tumor thickness now contribute to clinical T classification.

So, information from older articles using previous TNM versions may not apply to patients staged with Version 9.

Stage I

Stage I corresponds to T1 N0 M0 disease.

The tumor remains relatively limited by Version 9 criteria, with no regional lymph-node involvement and no distant metastasis.

Stage II

Stage II includes T2 N0 M0 and T1 N1 M0 disease.

The cancer may therefore have greater local pleural involvement without lymph-node spread, or relatively limited primary disease with involvement of certain ipsilateral regional lymph nodes.

Stage IIIA

Stage IIIA includes T1 N2 M0, T2 N1–N2 M0, and T3 with any N category, M0.

This group includes many different situations, so treatment decisions should not be made based only on the stage label.

Stage IIIB

Stage IIIB corresponds to T4, any N, M0.

T4 disease involves extensive invasion into structures that generally makes complete macroscopic surgical removal unrealistic.

Stage IV

Stage IV is defined by M1 distant metastatic disease, regardless of T or N category.

Examples can include spread to distant organs or other distant anatomical sites. Our complete mesothelioma stages guide covers each stage individually, including dedicated guides to Stage 1, Stage 2, Stage 3, and Stage 4 mesothelioma.

Treatment of Pleural Mesothelioma

There is no one-size-fits-all treatment plan for pleural mesothelioma.

Treatment choices depend on many factors, such as stage, type of mesothelioma, whether surgery is possible, symptoms, overall health, past treatments, patient preferences, and available clinical trials.

Today, treatment often includes systemic therapy.

For some patients, surgery or radiation may also be part of a broader treatment plan. Our treatment guide covers the full range of approaches used across all stages.

Immunotherapy with nivolumab and ipilimumab

Nivolumab and ipilimumab are immune-checkpoint inhibitors that target different mechanisms used by cancer cells to suppress immune responses.

The phase III CheckMate 743 trial compared first-line nivolumab plus ipilimumab with platinum-pemetrexed chemotherapy in previously untreated patients with unresectable pleural mesothelioma.

The original analysis demonstrated longer overall survival with nivolumab plus ipilimumab. Long-term follow-up has since strengthened the evidence that a subset of patients can experience durable benefit.

In the 2026 five-year analysis, overall survival at five years was 14% with nivolumab plus ipilimumab compared with 6% with chemotherapy in the trial population.

These are group-level survival estimates, not predictions for an individual patient. A person’s outlook depends on many additional clinical factors.

The FDA has approved nivolumab plus ipilimumab as first-line treatment for adults with unresectable malignant pleural mesothelioma.

Immune-checkpoint inhibitors can cause inflammatory side effects when activated immune cells affect healthy organs. Treatment therefore requires monitoring by clinicians experienced with immunotherapy.

Pembrolizumab with platinum and pemetrexed

Another first-line strategy combines immunotherapy with chemotherapy.

The phase III KEYNOTE-483 trial studied pembrolizumab added to platinum-pemetrexed chemotherapy in previously untreated advanced pleural mesothelioma.

Median overall survival in the study was 17.3 months with pembrolizumab plus chemotherapy versus 16.1 months with chemotherapy alone. The objective response rate was 52% versus 29%.

In September 2024, the U.S. Food and Drug Administration approved pembrolizumab with pemetrexed and platinum chemotherapy as first-line treatment for adults with unresectable advanced or metastatic malignant pleural mesothelioma.

Again, the median survival from a clinical trial is not the same as an individual’s expected lifespan. Some people live less time, while others live much longer.

Chemotherapy

Platinum-based chemotherapy remains an important part of pleural mesothelioma treatment.

The traditional backbone consists of pemetrexed combined with a platinum drug, usually cisplatin or, in appropriate circumstances, carboplatin.

Chemotherapy can reduce tumor burden or slow disease progression in some patients. It may be given alone or as part of an immunotherapy-containing regimen, depending on the clinical situation.

Choosing the best first treatment is not just about which trial showed the longest survival. The type of mesothelioma, other health problems, side effects, kidney function, and patient preferences all play a role.

This is why the oncology team should tailor treatment to each patient.

What Is the Role of Surgery?

Whether major surgery should be used to remove as much tumor as possible in pleural mesothelioma is now one of the most debated topics in treatment.

Historically, surgical strategies have included pleurectomy/decortication (P/D), extended pleurectomy/decortication (eP/D), and extrapleural pneumonectomy (EPP).

Pleurectomy/decortication removes pleural tumor while preserving the lung. Extended P/D may additionally remove involved portions of structures such as the diaphragm or pericardium when necessary.

Extrapleural pneumonectomy is a bigger operation that removes the affected lung, pleura, and other involved tissues. This surgery is now used much less often.

Why the evidence changed

Historically, much of the evidence supporting aggressive surgery came from highly selected patients treated at specialist centers rather than randomized trials.

The phase III MARS 2 randomized trial provided important new evidence. In patients considered to have resectable disease, adding extended pleurectomy/decortication to chemotherapy was associated with worse survival during the study period and more serious adverse events compared with chemotherapy alone.

These results have changed how doctors talk about surgery for pleural mesothelioma.

Current ASCO guidance does not recommend surgical cytoreduction solely because a tumor appears anatomically resectable. Surgery may still be considered for highly selected patients with favorable features, particularly clinically early-stage T1–3 N0 epithelioid disease, after comprehensive staging and multidisciplinary review at an experienced center.

When surgery is considered, lung-sparing approaches are generally preferred over extrapleural pneumonectomy.

If you are thinking about major surgery, it is best to have your case reviewed at a center with experience in pleural mesothelioma. There, you can discuss the benefits, risks, and other options in detail.

Radiation therapy

Radiation therapy can be used in different ways for pleural mesothelioma, but whether it is used depends a lot on each person’s situation.

It may be considered to relieve localized pain or other symptoms caused by tumor growth. In selected specialist-center treatment strategies, radiation may also form part of multimodality management.

Treating the whole pleural surface with radiation is difficult because important organs like the remaining lung, heart, spinal cord, and liver are close by.

Modern techniques allow radiation oncologists to target treatment more precisely, but radiation therapy is not generally used as a standalone curative treatment for pleural mesothelioma.

Managing pleural effusion and other symptoms

Treatments aimed at the cancer and those aimed at symptoms work together and are not in competition.

Pleural effusion can compress the lung and contribute substantially to breathlessness.

Thoracentesis can temporarily remove fluid from the pleura. If the fluid keeps coming back, doctors may suggest options like a permanent catheter or pleurodesis, depending on your symptoms, lung function, overall health, and preferences.

Other supportive treatments can help with pain, breathlessness, tiredness, appetite, movement, sleep, and emotional or practical issues.

Palliative care does not mean stopping cancer treatment.

Palliative care focuses on managing symptoms, improving quality of life, and supporting patients and families.

It can be started while you are still getting active cancer treatment.

Palliative care and hospice are not the same. Hospice is for a different stage and goal of care, while palliative care can be helpful much earlier during cancer treatment.

Clinical trials

Clinical trials are especially important for rare cancers like pleural mesothelioma.

Researchers are investigating new immune-based strategies, treatment combinations, targeted approaches, cellular therapies, biomarkers and different ways of sequencing existing treatments.

A trial’s eligibility requirements may depend on previous therapy, histology, stage, tumor biomarkers, organ function, performance status and many other factors.

A website cannot tell if a specific patient qualifies for a clinical trial.

If you are interested in joining a research study, talk to your oncology team and check official registries like ClinicalTrials.gov.

Pleural Mesothelioma Prognosis

The outlook for pleural mesothelioma can be very different from one person to another.

Important factors can include stage, histologic subtype, lymph-node involvement, performance status, overall health, age, tumor burden, resectability, and response to treatment.

Epithelioid mesothelioma usually has a better outlook than sarcomatoid or biphasic types, but the type alone cannot predict what will happen to each person.

Current population survival statistics

The American Cancer Society currently reports U.S. SEER five-year relative survival estimates for people diagnosed with pleural mesothelioma from 2015 through 2021:

These figures require careful interpretation.

SEER localized, regional, and distant categories are not the same as AJCC Stage I, II, III, and IV.

These statistics are based on people treated in the past. Since treatments have changed with new immunotherapy and chemoimmunotherapy, older survival data may not show what happens to patients diagnosed today.

Most importantly, survival statistics are about groups of people and cannot predict how long any one person will live.

For a deeper explanation, see our complete guide to Mesothelioma Prognosis and Survival.

Why specialist care can matter

Pleural mesothelioma involves several different medical specialties.

An experienced multidisciplinary team may include medical oncology, thoracic surgery, radiation oncology, pulmonology, thoracic radiology, pathology, interventional pulmonology and palliative-care specialists.

Specialist evaluation can be particularly valuable for confirming pathology, interpreting Version 9 staging, determining whether surgery deserves consideration, selecting systemic treatment, managing recurrent pleural effusion and identifying appropriate clinical trials.

Getting a second opinion does not mean you have to switch all your care to another hospital. Sometimes, a specialist center can review your case while you continue most of your treatment closer to home.

Questions to Ask Your Medical Team

1. Has my diagnosis been reviewed by a pathologist experienced in pleural mesothelioma?
2. What histologic subtype do I have?
3. What is my TNM Version 9 stage?
4. Has the cancer spread to regional lymph nodes or distant organs?
5. Is my disease considered resectable or unresectable, and what factors led to that conclusion?
6. What is the main goal of treatment in my situation?
7. Which first-line systemic treatment options are reasonable to discuss?
8. What potential benefits and side effects are most relevant to me?
9. If surgery is being considered, how does current evidence such as MARS 2 apply to my case?
10. Would review at a multidisciplinary mesothelioma center be useful?
11. Are there clinical trials that fit my diagnosis and previous treatment?
12. What can be done now to manage breathlessness, pleural effusion, pain, or other symptoms?

Frequently Asked Questions

References

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2. National Cancer Institute. Asbestos Exposure and Cancer Risk Fact Sheet. National Cancer Institute.
3. PDQ Adult Treatment Editorial Board. Malignant Mesothelioma Treatment (PDQ®), Health Professional Version. National Cancer Institute. Updated 2025.
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9. Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma: CheckMate 743. The Lancet. 2021;397:375–386. doi:10.1016/S0140-6736(20)32714-8.
10. Scherpereel A, Baas P, Nowak AK, et al. Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743. Journal of Clinical Oncology. 2026;44:742–749. doi:10.1200/JCO-25-01328.
11. U.S. Food and Drug Administration. FDA approval of nivolumab in combination with ipilimumab for first-line treatment of unresectable malignant pleural mesothelioma. 2020.
12. Chu Q, Perrone F, Greillier L, et al. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma: a phase 3 randomized trial. The Lancet. 2023. doi:10.1016/S0140-6736(23)01613-6.
13. U.S. Food and Drug Administration. FDA approves pembrolizumab with pemetrexed and platinum chemotherapy for unresectable advanced or metastatic malignant pleural mesothelioma. September 17, 2024.
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