Mesothelioma treatment typically combines several approaches: chemotherapy, surgery, radiation, and increasingly, immunotherapy. The specific plan depends on the type of mesothelioma (pleural or peritoneal), how advanced it is, and whether a patient is healthy enough for surgery. Average survival with treatment is about 18 months from diagnosis, and the five-year survival rate for pleural mesothelioma ranges from 7% to 24% depending on stage.
Immunotherapy as a First-Line Option
In October 2020, the FDA approved a combination of two immunotherapy drugs (nivolumab plus ipilimumab) as a first-line treatment for pleural mesothelioma that can’t be surgically removed. These drugs work by helping the immune system recognize and attack cancer cells. In the trial that led to approval, patients on the immunotherapy combination had a median overall survival of 18.1 months, compared to 14.1 months for those receiving standard chemotherapy. That translated to a 26% reduction in the risk of death.
This approval was a significant shift. For nearly two decades, chemotherapy had been the only standard first-line option. Now, immunotherapy is a viable alternative, particularly for patients whose tumors have non-epithelioid cell types, which tend to respond less well to chemotherapy.
Chemotherapy
The standard chemotherapy combination pairs two drugs given intravenously every 21 days. Treatment continues until the cancer progresses or side effects become unmanageable. There’s no fixed number of cycles. Before each infusion, patients take folic acid supplements and receive a vitamin B-12 injection to reduce side effects like severe mouth sores and low blood counts. A steroid is also taken for three days around each treatment to help prevent skin reactions.
Chemotherapy remains the backbone of treatment for patients who aren’t surgical candidates and may also be used before surgery to shrink tumors or after surgery to target any remaining cancer cells.
Surgery for Pleural Mesothelioma
Two main surgical options exist for pleural mesothelioma, and they differ dramatically in scope. The more aggressive approach, extrapleural pneumonectomy (EPP), removes the entire affected lung along with the lining of the chest wall, the diaphragm, and the sac around the heart. The lung-sparing alternative, pleurectomy/decortication (P/D), removes the tumor and the chest lining but leaves the lung intact.
P/D has become the preferred option at many centers. In a study covering nearly two decades of surgical data, perioperative mortality was 11% for EPP compared to 0% for P/D. Median survival was also longer with P/D: 22 months versus 15 months for EPP after accounting for surgical deaths. National guidelines now suggest P/D is potentially safer for patients with early-stage disease and the epithelioid cell type, which is the most common form.
Not everyone is a candidate for either surgery. Eligibility depends on the cancer’s stage, cell type, and the patient’s lung and heart function. Surgery is almost always combined with chemotherapy and sometimes radiation as part of a broader treatment plan.
How Treatments Are Combined
The most intensive approach, called trimodal therapy, layers all three conventional treatments together in a specific sequence. The typical order starts with chemotherapy (two to three cycles), followed by restaging scans to check the tumor’s response. If the cancer has responded or stayed stable, surgery follows three to six weeks later. Radiation to the affected side of the chest begins six to twelve weeks after surgery.
A different sequencing strategy, called SMART (Surgery for Mesothelioma After Radiation Therapy), flips the order of radiation and surgery. Patients receive a concentrated, five-day course of high-dose radiation to the entire affected side of the chest, followed by surgery within about a week. This approach aims to sterilize the tumor edges before the surgeon operates, potentially reducing the risk of cancer seeding during the procedure. In phase 2 trial results, the most common sites where cancer later returned were the opposite chest (46% of recurrences) and the abdominal lining (44%).
Treatment for Peritoneal Mesothelioma
Mesothelioma that develops in the abdominal lining is treated differently from the pleural form. The standard approach combines cytoreductive surgery, where surgeons remove as much visible tumor as possible from the abdominal cavity, with heated chemotherapy delivered directly into the abdomen during the operation. This technique, called HIPEC, bathes the abdominal cavity in warm chemotherapy solution to kill microscopic cancer cells that surgery alone can’t address.
Outcomes for peritoneal mesothelioma treated this way are generally better than for the pleural form. Median survival in a large study was 3.2 years from the first operation. Among patients who completed the full treatment protocol (surgery plus two rounds of heated chemotherapy), about one-third were still alive at the median follow-up of 3.4 years. Completing the full course made a substantial difference: patients who received both rounds of heated chemotherapy had significantly better outcomes than those who received only one.
Managing Fluid Buildup
One of the most debilitating symptoms of pleural mesothelioma is fluid accumulating between the lung and chest wall, which causes progressive breathlessness. Two main strategies address this, and both are equally effective at relieving shortness of breath.
Talc pleurodesis is an inpatient procedure where talc is delivered into the chest cavity after draining the fluid. The talc irritates the surfaces of the lung and chest wall, causing them to stick together and preventing fluid from reaccumulating. It works in 70% to 75% of cases, with side effects like pain, fever, and infection occurring in fewer than 10% of patients.
The alternative is an indwelling pleural catheter, a thin tube with a one-way valve placed into the chest cavity during a short outpatient procedure. It allows fluid to be drained at home, typically by a visiting nurse or caregiver, as often as needed. About half of patients with these catheters find that the lung and chest wall naturally seal together within three months of daily drainage, eliminating the need for further draining. Infection rates are around 8%, and catheter blockage occurs in about 5% of cases.
The choice between the two often comes down to lung function. If the lung can fully re-expand after fluid drainage, either option works well. If the lung is “trapped” and can’t expand properly, a catheter is the better choice because talc pleurodesis rarely works in that situation.
Tumor Treating Fields
A newer technology uses low-intensity electric fields delivered through adhesive pads placed on the chest to disrupt dividing cancer cells. The device, called Optune Lua, is worn for as many hours per day as possible and used alongside standard chemotherapy. In a phase 2 study called STELLAR, patients treated with the combination had a median overall survival of 18.2 months, which compared favorably to historical chemotherapy-only results. The FDA cleared this device for mesothelioma, though the evidence is still based on a single-arm trial without a direct comparison group.
Survival by Stage
Prognosis varies considerably. The American Cancer Society reports five-year survival rates for pleural mesothelioma ranging from 24% for localized disease down to 7% for more advanced stages. Several factors influence individual outcomes beyond stage: epithelioid cell type responds better to treatment than sarcomatoid or biphasic types, younger age and better overall health allow for more aggressive treatment, and peritoneal mesothelioma generally carries a better prognosis than pleural disease. Patients treated at specialized mesothelioma centers, where surgical teams perform higher volumes of these complex operations, also tend to have better outcomes.