Mesothelioma Treatment Options in 2026: Surgery, Chemo, Immunotherapy

Multimodal Treatment Approach

The most effective mesothelioma treatment strategies combine multiple therapies — an approach known as multimodal treatment. For eligible patients, this typically involves some combination of surgery, chemotherapy, radiation therapy, and increasingly, immunotherapy. The specific treatment plan depends on the type and stage of mesothelioma, the patient's overall health and age, and the cell type of the tumor.

Treatment decisions should be made in consultation with a multidisciplinary team at a specialized mesothelioma treatment center. These centers have the highest volume of cases, the most experienced surgeons, and access to the latest clinical trials. Major mesothelioma treatment centers include Brigham and Women's Hospital in Boston, MD Anderson Cancer Center in Houston, Memorial Sloan Kettering in New York, and the University of Chicago Medicine.

Surgical Options

Surgery offers the best chance of long-term survival for patients with early-stage mesothelioma. The two primary surgical procedures for pleural mesothelioma are extrapleural pneumonectomy (EPP) and pleurectomy with decortication (P/D).

EPP is the more radical procedure, removing the affected lung, the pleural lining, the diaphragm on the affected side, and the pericardium. While aggressive, EPP can achieve significant tumor removal and is sometimes combined with heated chemotherapy wash. P/D is a lung-sparing surgery that removes the pleural lining and all visible tumor while preserving the lung itself. P/D has become increasingly favored due to lower mortality rates and comparable survival outcomes to EPP in many studies.

For peritoneal mesothelioma, cytoreductive surgery (CRS) combined with HIPEC (hyperthermic intraperitoneal chemotherapy) has dramatically improved outcomes. During this procedure, surgeons remove all visible tumor from the abdominal cavity, then bathe the area in heated chemotherapy solution to kill remaining microscopic cancer cells. Five-year survival rates exceeding 50% have been reported with this approach.

Chemotherapy and Radiation

The standard first-line chemotherapy regimen for mesothelioma is pemetrexed (Alimta) combined with cisplatin or carboplatin. This combination has been the backbone of mesothelioma chemotherapy since its FDA approval in 2004. Response rates — meaning the tumor shrinks or stabilizes — are approximately 40-45%.

Radiation therapy is typically used as part of a multimodal approach rather than as a standalone treatment. Intensity-modulated radiation therapy (IMRT) allows precise targeting of tumor tissue while minimizing damage to surrounding organs. Radiation is commonly used after surgery to kill any remaining cancer cells, to shrink tumors before surgery (neoadjuvant therapy), or for palliative symptom relief in advanced cases.

Immunotherapy: The Breakthrough

Immunotherapy has emerged as the most significant treatment advance for mesothelioma in recent years. In October 2020, the FDA approved the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) as first-line treatment for unresectable pleural mesothelioma. This was the first new systemic treatment approval for mesothelioma in 16 years.

These drugs are checkpoint inhibitors — they work by releasing the brakes on the immune system, allowing it to recognize and attack cancer cells. In the CheckMate 743 clinical trial, the nivolumab-ipilimumab combination demonstrated a median overall survival of 18.1 months compared to 14.1 months for chemotherapy alone. For patients with non-epithelioid cell types — which historically have the worst outcomes — the benefit was even more pronounced.

Ongoing clinical trials are investigating numerous other immunotherapy approaches for mesothelioma, including CAR-T cell therapy, tumor-treating fields (TTFields, marketed as Optune Lua), pembrolizumab (Keytruda), and various combination therapies. Patients should discuss clinical trial eligibility with their treatment team, as these trials offer access to potentially life-extending therapies not yet widely available.