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Mesothelioma Treatment Options

Modern mesothelioma treatment uses a multimodal approach — combining surgery, chemotherapy, immunotherapy, and radiation — to extend survival and improve quality of life. Significant advances in immunotherapy and surgical techniques have expanded options for patients at every stage.

18.1 mo Median OS with Immunotherapy
~40% Chemo Response Rate
5 yr+ Survival with Multimodal Tx
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Medically reviewed and updated: • Sources: NCI, NCCN, FDA, NEJM, The Lancet

Overview of Mesothelioma Treatment

Mesothelioma treatment has evolved significantly with new surgical techniques, targeted chemotherapy, and the landmark approval of immunotherapy in 2020. Today, treatment for mesothelioma follows a multimodal approach — combining two or more modalities for the best possible outcome.

The specific treatment plan depends on several critical factors:

  • Stage of the cancer — earlier stages (I and II) offer more options, including curative-intent surgery
  • Cell type (histology) — epithelioid responds best to treatment; sarcomatoid and biphasic are more resistant to chemo but may respond well to immunotherapy
  • Tumor location — pleural (lung lining), peritoneal (abdominal lining), pericardial (heart lining), or tunica vaginalis
  • Overall patient health — age, lung function, cardiac health, and performance status determine surgical candidacy

The Multimodal Standard of Care

The NCCN guidelines recommend multimodal therapy as the standard of care. Common approaches include surgery + chemotherapy + radiation (trimodal), surgery + neoadjuvant or adjuvant chemotherapy, immunotherapy alone or with chemotherapy for unresectable disease, and chemotherapy + radiation for non-surgical patients.

Treatment Is Highly Individualized

No two mesothelioma cases are identical. A thorough evaluation at a specialized mesothelioma treatment center — including imaging, biopsy, staging, and pulmonary function testing — is essential before any treatment plan is developed. Patients should seek evaluation at a cancer center with dedicated mesothelioma experience, as this cancer requires specialized surgical and oncological expertise. Learn more about mesothelioma diagnosis and staging.

3,000 New U.S. Cases Per Year
12–21 mo Median Survival (All Stages)
5+ yrs Possible with Multimodal Tx
80% Caused by Asbestos Exposure

Surgery for Mesothelioma

Surgery remains the cornerstone of curative-intent treatment. The goal is to achieve macroscopic complete resection (MCR) — removing as much visible tumor as possible. Two primary procedures are used for pleural mesothelioma, and a distinct approach exists for peritoneal mesothelioma.

Extrapleural Pneumonectomy (EPP)

EPP is the most radical surgical option for pleural mesothelioma. It involves the removal of the entire affected lung, along with the visceral and parietal pleura, the ipsilateral diaphragm, and the ipsilateral pericardium. The diaphragm and pericardium are then reconstructed with prosthetic patches. The surgical mortality rate is approximately 5–7% at experienced centers, and the procedure requires patients to be in good overall health with adequate pulmonary reserve in the remaining lung.

Pleurectomy/Decortication (P/D)

P/D is a lung-sparing surgery that has become the preferred surgical approach at most major mesothelioma centers. The procedure removes the diseased parietal and visceral pleura along with all visible tumor, but preserves the underlying lung. Extended P/D may also include resection of the diaphragm and pericardium when tumor involvement requires it.

P/D offers several advantages over EPP: preserved lung function, lower surgical mortality (approximately 2–4%), faster recovery, and comparable or superior long-term survival in most studies.

Factor EPP (Extrapleural Pneumonectomy) P/D (Pleurectomy/Decortication)
What Is Removed Entire lung + pleura + diaphragm + pericardium Pleura + visible tumor; lung preserved
Surgical Mortality 5–7% 2–4%
Lung Function Permanently lost (one lung removed) Preserved (may be reduced)
Hospital Stay 10–14 days typical 7–10 days typical
Median Survival 12–22 months 16–30 months
Quality of Life Significantly reduced respiratory capacity Better preserved respiratory function
Adjuvant Radiation Easier to deliver (no lung in field) More technically challenging (lung in field)
Current Trend Declining use at most centers Preferred at most centers

CRS + HIPEC for Peritoneal Mesothelioma

For patients with peritoneal mesothelioma (affecting the abdominal lining), the standard surgical approach is cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC). The surgeon removes all visible tumor from the abdominal cavity, then bathes the area with heated chemotherapy solution (typically cisplatin at 42°C) to destroy residual microscopic cancer cells. CRS + HIPEC has produced the best outcomes of any mesothelioma treatment, with median survival exceeding 5 years in selected patients with epithelioid histology and complete cytoreduction.

Surgical Candidacy Criteria

Not all mesothelioma patients are candidates for curative-intent surgery. General criteria include stage I–III disease, epithelioid or biphasic cell type, adequate cardiopulmonary function, good performance status (ECOG 0–1), and no distant metastases. Evaluation at a specialized mesothelioma center is essential, as surgical outcomes are significantly better at high-volume centers.

Seek a Specialized Mesothelioma Surgeon

Mesothelioma surgery requires highly specialized expertise. Patients should seek evaluation at a National Cancer Institute-designated cancer center or a hospital with a dedicated mesothelioma program. If you need help identifying a treatment center, contact us for a free consultation — our team can connect you with leading specialists.

Chemotherapy for Mesothelioma

Chemotherapy uses anti-cancer drugs to kill mesothelioma cells throughout the body. It serves as primary treatment for non-surgical candidates, as neoadjuvant therapy (before surgery) to shrink tumors, or as adjuvant therapy (after surgery) to target remaining cancer cells.

First-Line Chemotherapy: Pemetrexed + Cisplatin

The standard first-line regimen is pemetrexed (Alimta) combined with cisplatin, established by the landmark EMPHACIS trial published in the New England Journal of Medicine in 2003:

  • Median survival of 12.1 months versus 9.3 months with cisplatin alone
  • Response rate of approximately 41% — tumor shrinkage in nearly half of patients
  • Improved time to progression of 5.7 months versus 3.9 months

For patients who cannot tolerate cisplatin, carboplatin is used as a substitute with comparable efficacy and a more favorable side effect profile, particularly for older patients or those with kidney concerns.

Neoadjuvant vs. Adjuvant Chemotherapy

Neoadjuvant chemotherapy is administered before surgery (typically 3–4 cycles of pemetrexed + cisplatin) to shrink the tumor and improve surgical outcomes. Adjuvant chemotherapy is given after surgery (typically 4–6 cycles) to target any microscopic cancer cells that may remain. The neoadjuvant approach also allows oncologists to assess tumor responsiveness to chemotherapy before committing to surgery.

Second-Line Options

When first-line chemotherapy fails, second-line options include gemcitabine (alone or in combination), vinorelbine, retreatment with pemetrexed for patients who had an initial response, and immunotherapy with nivolumab + ipilimumab, which is increasingly used as second-line therapy.

Common Side Effects

Chemotherapy side effects commonly include fatigue, nausea, decreased appetite, low blood counts (neutropenia, anemia, thrombocytopenia), kidney effects (with cisplatin), and neuropathy. Folic acid and vitamin B12 supplementation is required with pemetrexed to reduce toxicity. Most side effects are manageable with supportive medications and dose adjustments.

Immunotherapy for Mesothelioma

Immunotherapy represents the most significant advance in mesothelioma treatment in nearly two decades. Unlike chemotherapy, which directly kills cancer cells, immunotherapy activates the patient's own immune system to recognize and attack mesothelioma cells.

Nivolumab + Ipilimumab (CheckMate 743)

In October 2020, the FDA approved nivolumab (Opdivo) + ipilimumab (Yervoy) for first-line treatment of unresectable malignant pleural mesothelioma, based on the CheckMate 743 trial published in The Lancet:

  • Median overall survival of 18.1 months with nivolumab + ipilimumab versus 14.1 months with standard chemotherapy (pemetrexed + platinum)
  • 2-year survival rate of 41% with immunotherapy versus 27% with chemotherapy
  • Particularly strong benefit in non-epithelioid histology — sarcomatoid and biphasic patients showed 18.1 months median OS with immunotherapy versus 8.8 months with chemotherapy
  • Durable responses — some patients continue to benefit from immunotherapy for years after treatment

Nivolumab (PD-1 inhibitor) and ipilimumab (CTLA-4 inhibitor) release two separate "brakes" on the immune system, enabling a robust anti-tumor response. Treatment typically involves ipilimumab every 6 weeks for up to 4 doses combined with nivolumab every 2 weeks for up to 2 years.

Pembrolizumab (Keytruda) Trials

Pembrolizumab is another PD-1 checkpoint inhibitor that has shown activity in mesothelioma clinical trials. The KEYNOTE-158 study demonstrated objective response rates in previously treated patients. While pembrolizumab does not yet have a specific FDA approval for mesothelioma, it is used in clinical practice and ongoing trials are evaluating it in combination with chemotherapy.

Emerging Immunotherapy Combinations

Active clinical research is exploring immunotherapy + chemotherapy combinations, neoadjuvant or adjuvant immunotherapy before or after surgery, dual immunotherapy + bevacizumab (anti-angiogenic therapy), and novel checkpoint targets including LAG-3 and TIGIT pathways.

18.1 mo Median OS (Nivo + Ipi)
41% 2-Year Survival Rate
Oct 2020 FDA Approval Date
2x OS Benefit in Non-Epithelioid

Radiation Therapy for Mesothelioma

Radiation therapy uses high-energy beams to kill cancer cells and shrink tumors. In mesothelioma, radiation is used as an adjuvant treatment after surgery, as palliative therapy for symptom relief, or as part of a trimodal approach. Radiation alone is not curative, but it plays an important supporting role in multimodal plans.

Intensity-Modulated Radiation Therapy (IMRT)

IMRT is the most commonly used radiation technique for mesothelioma. It uses computer-controlled linear accelerators to deliver precise radiation doses that conform to the three-dimensional shape of the tumor while minimizing exposure to surrounding healthy tissues — particularly the lungs, heart, and liver. IMRT is especially valuable after P/D surgery, where the lung remains in place and must be protected from radiation damage.

Adjuvant Radiation After Surgery

Following EPP (where the lung has been removed), radiation can be delivered to the entire hemithorax at higher doses because there is no remaining lung tissue to protect. After P/D (where the lung is preserved), radiation delivery is more technically challenging and requires IMRT or other precision techniques to avoid damaging the preserved lung.

SMART Technique

The Surgery for Mesothelioma After Radiation Therapy (SMART) approach reverses the traditional sequence by delivering high-dose, short-course radiation before surgery. Developed at Princess Margaret Cancer Centre in Toronto, SMART involves 5 consecutive days of high-dose hemithoracic radiation followed by EPP within one week. Early results have shown improved local control and promising survival outcomes in selected patients.

Palliative Radiation

For patients who are not candidates for curative-intent treatment, radiation therapy can provide significant symptom relief — reducing chest wall pain, relieving shortness of breath caused by tumor compression, preventing tumor growth at biopsy or surgical port sites (prophylactic tract irradiation), and managing symptoms from metastatic disease.

Clinical Trials for Mesothelioma

Clinical trials test new treatments and drug combinations in mesothelioma patients. Because mesothelioma is a rare cancer with limited approved therapies, clinical trials play an especially important role — every currently approved treatment, including pemetrexed chemotherapy and nivolumab + ipilimumab, was developed through clinical trials.

Why Clinical Trials Matter

Clinical trials offer mesothelioma patients access to cutting-edge treatments not yet available outside of clinical research, close medical monitoring by specialized oncology teams, treatment at leading cancer centers, and no additional cost for the investigational treatment (study drugs and related tests are provided at no charge).

How to Find Mesothelioma Clinical Trials

  • ClinicalTrials.gov — the U.S. National Library of Medicine's registry of all clinical studies; search for "mesothelioma" to see active trials
  • Your oncologist — ask your mesothelioma specialist about trials available at their institution or through cooperative group networks
  • National Cancer Institute (NCI) — maintains a list of NCI-supported mesothelioma clinical trials
  • Major cancer centers — MD Anderson, Memorial Sloan Kettering, Brigham and Women's, and Moffitt regularly enroll patients in mesothelioma trials

Current Areas of Active Research

The most active areas of mesothelioma clinical trial research include combination immunotherapy regimens, immunotherapy plus chemotherapy, neoadjuvant and adjuvant immunotherapy in surgical patients, tumor treating fields (TTFields), targeted therapies based on tumor genomic profiling, CAR-T cell therapy, and novel drug delivery methods.

Clinical Trial Eligibility

Each clinical trial has specific eligibility criteria, including the type and stage of mesothelioma, prior treatments received, overall health status, and sometimes specific biomarkers. Many trials accept patients who have already received prior treatment. If standard treatments are no longer working, a clinical trial may offer additional options. Ask your oncologist or contact us for help identifying trials you may be eligible for.

Emerging & Experimental Treatments

Several experimental approaches beyond standard surgery, chemotherapy, immunotherapy, and radiation are showing promise. While not yet standard of care, these represent the future direction of mesothelioma therapy and are available through clinical trials at select centers.

Tumor Treating Fields (TTFields / Optune)

TTFields uses low-intensity, alternating electric fields delivered through transducer arrays worn on the chest to disrupt cancer cell division. The STELLAR trial showed a median overall survival of 18.2 months when combined with chemotherapy — comparable to immunotherapy results. TTFields received FDA Humanitarian Device Exemption approval for mesothelioma (NovoTTF-100L / Optune Lua).

Gene Therapy

Gene therapy delivers therapeutic genes directly into tumor cells to make them more vulnerable to the immune system or to chemotherapy. Adenovirus-mediated gene therapy using the interferon-alpha gene has been studied in mesothelioma clinical trials, with some patients showing tumor regression and improved survival.

Photodynamic Therapy (PDT)

PDT involves administering a light-sensitive drug that accumulates in cancer cells, then activating the drug with a specific wavelength of light during surgery to destroy residual tumor cells. PDT has been studied as an intraoperative adjunct to P/D surgery at the University of Pennsylvania, with early results showing improved local control.

CAR-T Cell Therapy

Chimeric antigen receptor T-cell (CAR-T) therapy engineers a patient's own immune cells to recognize and attack specific proteins on mesothelioma cells. Researchers have developed CAR-T cells targeting mesothelin — a protein highly expressed on mesothelioma cells — with clinical trials underway at Memorial Sloan Kettering and other institutions. Early-phase results have shown that CAR-T cells can infiltrate mesothelioma tumors and produce anti-tumor responses.

Experimental Treatments Require Specialized Centers

These emerging treatments are only available at select research institutions and through clinical trials. Patients interested in experimental therapies should consult with a mesothelioma specialist who can evaluate eligibility and provide referrals. Not all experimental treatments are appropriate for every patient, and participation in clinical trials is voluntary.

Legal Rights & Paying for Treatment

Mesothelioma treatment is expensive — surgery can exceed $50,000, and immunotherapy drugs like nivolumab and ipilimumab can cost over $100,000 per year. These costs place an enormous burden on patients and families already dealing with a devastating diagnosis.

Because mesothelioma is caused by asbestos exposure, patients and their families have legal rights to compensation from the companies that manufactured, distributed, and used asbestos-containing products. This compensation can cover medical treatment costs, lost income, travel to specialized centers, pain and suffering, and wrongful death claims for surviving families.

Sources of Compensation

  • Asbestos trust funds — over $30 billion remains available across 60+ active trusts established by bankrupt asbestos companies
  • Personal injury lawsuits — claims against asbestos manufacturers that are still operating
  • VA disability benefits — for military veterans exposed to asbestos during service (typically rated at 100% for mesothelioma)
  • Workers' compensation — benefits for occupational asbestos exposure
  • Wrongful death claims — available to surviving spouses, children, and dependents

No Upfront Legal Costs

Mesothelioma attorneys work on a contingency fee basis, which means you pay no upfront costs and no legal fees unless compensation is recovered on your behalf. Filing a legal claim does not interfere with your medical treatment — in fact, compensation from legal claims can help you access the best available treatment at specialized centers. Learn more about your compensation options or request a free case review below.

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FAQ answers reviewed by legal team:

Frequently Asked Questions About Mesothelioma Treatment

What is the most effective treatment for mesothelioma?

The most effective treatment is a multimodal approach combining surgery, chemotherapy, and radiation or immunotherapy. For surgical candidates, pleurectomy/decortication (P/D) followed by chemotherapy and radiation has shown the best outcomes, with some patients surviving 5 years or longer. For unresectable disease, nivolumab + ipilimumab immunotherapy demonstrated 18.1 months median overall survival in the CheckMate 743 trial. Treatment is always individualized based on cancer stage, cell type, tumor location, and patient health.

What is the difference between EPP and P/D surgery?

Extrapleural pneumonectomy (EPP) removes the entire affected lung along with the pleura, diaphragm, and pericardium. Pleurectomy/decortication (P/D) is a lung-sparing surgery that removes the diseased pleural lining and visible tumors while preserving the lung. P/D has become preferred at most major mesothelioma centers because it offers similar survival with lower surgical mortality (2–4% vs. 5–7% for EPP) and better quality of life.

Is immunotherapy approved for mesothelioma?

Yes. In October 2020, the FDA approved nivolumab (Opdivo) + ipilimumab (Yervoy) for unresectable malignant pleural mesothelioma based on the CheckMate 743 trial, which showed 18.1 months median overall survival versus 14.1 months with chemotherapy. The benefit was particularly strong in non-epithelioid (sarcomatoid and biphasic) cell types, where immunotherapy approximately doubled median survival.

Can mesothelioma patients access clinical trials?

Yes. Clinical trials are available at major cancer centers across the United States. Active research areas include combination immunotherapy, tumor treating fields (TTFields), CAR-T cell therapy, gene therapy, and photodynamic therapy. Search ClinicalTrials.gov or ask your oncologist about eligibility. Many trials accept patients who have already received prior treatment. Contact us for help connecting with leading treatment centers.

This page was last reviewed and updated on by the legal and medical team at Danziger & De Llano, LLP.

Sources & References

  1. Vogelzang NJ et al. — Phase III Study of Pemetrexed in Combination with Cisplatin versus Cisplatin Alone in Patients with Malignant Pleural Mesothelioma (EMPHACIS Trial), NEJM 2003
  2. Baas P et al. — First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743), The Lancet 2021
  3. NCCN Clinical Practice Guidelines in Oncology — Malignant Pleural Mesothelioma
  4. National Cancer Institute — Mesothelioma Treatment (PDQ) — Health Professional Version
  5. FDA — Approval of Nivolumab and Ipilimumab for Unresectable Malignant Pleural Mesothelioma (October 2020)
  6. Flores RM et al. — Extrapleural Pneumonectomy Versus Pleurectomy/Decortication in the Surgical Management of Malignant Pleural Mesothelioma, Journal of Clinical Oncology
  7. NCI SEER Program — Mesothelioma Cancer Stat Facts

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