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Multimodal Therapy for Mesothelioma

Mesothelioma is a complex form of cancer and is often treated using multimodal therapy. This employs different treatment modalities, including surgery, chemotherapy, and radiation therapy, to increase the patient’s survival rates. Not all patients are candidates for this kind of treatment.


Medically Reviewed By:
Patricia Shelton, M.D.

Patricia Shelton

Medically Reviewed By:Patricia Shelton, M.D.

Mesothelioma is most commonly treated using multimodal therapy, which employs multiple different treatment modalities. This is the most effective way to treat mesothelioma and increases survival rates. Multimodal therapy is an aggressive form of cancer treatment, and not all patients are candidates for using this strategy.

Treatments Used in Multimodal Therapy

Multimodal therapy involves using a combination of different treatment methods in order to eliminate as much of the cancer as possible with the goal of extending the patient’s life expectancy. This form of treatment can significantly extend survival in some patients, although mesothelioma is still considered to be incurable. It’s rare that treatment will completely eliminate all of the cancer, although there have been some reported cases of long-term remission. Multimodal therapy can also be called multimodality therapy; these two terms are interchangeable.

The primary treatments used in multimodal therapy include surgery, chemotherapy and radiation therapy. Other forms of treatment, such as immunotherapy and Tumor Treating Fields (TTF), are not generally part of the main treatment plan but may be used if the primary treatments fail or if the cancer later progresses.

A 2021 study indicated that pleural mesothelioma patients who were treated using multimodal therapy had a median survival time of 32 months, compared with 10 months in those who received only medical treatment. Because of the results of studies like this, most experts recommend multimodal therapy for those patients who are eligible for it.

Most patients receive multimodal therapy at a cancer center. This allows access to the multiple different specialists who will need to be involved in the patient’s care, including medical oncologists, surgeons and radiation oncologists. With a rare type of cancer such as mesothelioma, it’s beneficial to choose a treatment team with expertise in treating this specific type of cancer to maximize the chances of a good outcome. The American Cancer Society also recommends getting a second opinion about your diagnosis before committing to a treatment plan.

Patient Eligibility for Multimodal Therapy

Multimodal therapy is an aggressive form of cancer treatment, and not all patients are considered to be good candidates. In determining whether a particular patient is eligible for multimodal therapy, the following factors are important:


Of the cancer. Multimodal therapy is most effective when the cancer is found in an earlier stage. Those in more advanced stages may not be eligible for this type of treatment.

Cell type

Of the cancer. Patients with sarcomatoid tumors are generally not considered good candidates for multimodal therapy because mesothelioma of this cell type spreads very easily and the treatment is less likely to be effective. Those with epithelioid tumors are considered to be the best candidates, and those with biphasic tumors may also be eligible.

Overall health

In order to undergo the aggressive treatments used in multimodal therapy, patients need to be in relatively good overall health so that the body will be able to heal from the effects of the treatments. Patients with multiple chronic diseases, or who are frail overall, may not be healthy enough to undergo these treatments.


Younger patients are more likely to be good candidates for multimodal therapy because older patients are less likely to be able to tolerate aggressive treatments. However, the patient’s medical condition is more important than their age; some older patients are healthy enough to be good candidates for multimodal therapy, while some younger ones are not.

Your oncologist will let you know whether he or she believes that you’re a good candidate for multimodal therapy, and why.

Although multimodal therapy will generally offer the best chances for the longest possible life expectancy, it’s still the patient’s choice whether they want to choose this aggressive form of treatment. Many patients choose to have multimodal therapy in order to maximize the amount of time they have with their loved ones. However, others choose to receive palliative care instead to focus on quality of life in their remaining time rather than enduring the side effects of aggressive cancer treatment. Each patient should talk through treatment options with their cancer care team and carefully consider their own values and goals for their cancer treatment. Ultimately, it’s the patient’s own choice which treatment options they want to pursue.

Multimodal Therapy for Pleural Mesothelioma

The specific treatment plan for pleural mesothelioma can vary somewhat from patient to patient. Treatments that may be part of multimodality therapy for pleural mesothelioma include:


Which may be extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D). These are invasive surgical methods that are intended to remove as much cancer tissue as possible. The surgeon also removes certain tissues that are likely to contain cancer cells; for example, in EPP, the entire lung on the affected side is removed.


Which may be given before, during and/or after surgery. These are medications that target cancer cells, making them unable to divide or causing them to die off. A combination of different chemotherapy agents is usually used, most often pemetrexed with cisplatin or carboplatin, which has been shown to offer a significant survival benefit in pleural mesothelioma patients.

Radiation therapy

Like with chemotherapy, radiotherapy can also be given before or after surgery. This uses high-energy beams to damage and destroy cancer cells in a particular area. Radiation can be targeted to a specific small area (for example, along an incision tract), or can be used more broadly (for example, on the entire half of the chest where the cancer originated).

Most commonly, multimodal therapy involves using all three of these types of treatments. The order in which the treatments are used differs from patient to patient. Research doesn’t clearly indicate that one specific way of performing multimodal therapy is superior to others, although clinical trials are currently investigating various ways of combining cancer therapies to discover which are the most effective.

Multimodal therapy involves up to three phases:

Neoadjuvant therapy

Which is used before surgery to shrink the tumor and make it easier to remove. Either chemotherapy or radiation therapy may be used as neoadjuvant therapy. A recent clinical trial showed that the use of neoadjuvant radiation therapy before extrapleural pneumonectomy resulted in three-year survival rates of 70 to 80 percent.


Which is generally the mainstay of treatment for patients who are eligible for it. In some cases, intraoperative chemotherapy (known as hyperthermic intrathoracic chemotherapy, or HITHOC) may be a part of the procedure; this is a newer treatment method, but studies suggest that it can extend survival by a few months. Photodynamic therapy (PDT) is another option that may be used during surgery; this method uses a drug that sensitizes cells to a particular wavelength of light, and then a light of this wavelength is shined within the thoracic cavity during the procedure.

Adjuvant therapy

Which is used after surgery to target any cancer cells that may have been left behind by surgery. Both chemotherapy and radiation therapy are potential adjuvant therapy methods; a particular patient may receive either one or both of these.

Neoadjuvant therapy is not always used. In some cases, a patient’s treatment plan may begin with surgery and then continue to one or more forms of adjuvant therapy. Others will start with either chemotherapy or radiation, followed by surgery, and then adjuvant treatment afterwards. The available evidence shows that adjuvant and neoadjuvant chemotherapy have approximately equal effectiveness overall.

The specifics of the treatment plan vary between different patients. Various patient factors as well as characteristics of the cancer will be considered when formulating the treatment plan. Different cancer centers also tend to use different protocols, although these can be adapted for different patients. Because mesothelioma is a rare form of cancer, it’s best to choose a cancer treatment team with experience in treating this specific malignancy.

Second-Line Treatments for Pleural Mesothelioma

In some patients, these methods are not successful in treating the cancer, or it recurs after a period of time. At this point, further rounds of chemotherapy and/or radiation therapy may be used. There are also some additional treatment options that may be used in these patients:
doctors in the OR
In general, if patients are eligible to have surgery along with adjuvant and/or neoadjuvant therapy, then this is the recommended treatment plan. Other treatments are generally recommended for patients who are not eligible for surgery, or those whose cancer has progressed after surgery.


Which stimulates the body’s own immune system to target and destroy cancer cells. Two forms of immunotherapy (Keytruda and Opdivo plus Yervoy) are currently FDA-approved for treating certain mesothelioma patients, including those whose disease has progressed following surgery and other treatments.

Tumor Treating Fields (TTF)

Which uses electrical impulses passed through the skin to disrupt the ability of cancer cells to divide and grow. Early studies have shown that this device can improve survival by a few months without significant side effects.

Clinical trials

Which are research studies to investigate a new treatment or combination of treatments. There are many different trials that are currently enrolling mesothelioma patients. A given trial usually has specific requirements in order to enroll, so you’ll want to talk with your treatment team to discover which ones you may be eligible for.

Multimodal Therapy for Peritoneal Mesothelioma

The most effective treatment for peritoneal mesothelioma is a multimodality treatment plan that combines surgery and chemotherapy. This is known as CRS-HIPEC, and it’s considered the gold standard of peritoneal mesothelioma treatment. Studies at various institutions have shown average life expectancy after the procedure of between 34 and 92 months, and five-year survival rates of 29 to 59 percent.

Doctor talking to older female patient in wheelchair
CRS-HIPEC combines two different treatment modalities in a single procedure:

Cytoreductive surgery (CRS)

This is a surgical technique in which the surgeon removes as much cancerous tissue as possible from the patient’s abdominal cavity. This may involve removing several organs or parts of organs, including the spleen, gallbladder, bladder and parts of the intestine. The specifics of tissue removal depend on where tumor tissue is found in a particular patient.

Hyperthermic intraperitoneal chemotherapy (HIPEC)

After the removal of tissue is complete, the abdomen is filled with a warmed solution of chemotherapy drugs. The heat helps to dilate blood vessels to encourage penetration of the chemotherapy into the tissues. After a period of time, the chemotherapy is washed out and the incisions are closed.

While radiation therapy is not commonly a major part of the treatment plan for peritoneal mesothelioma patients, adjuvant radiation along the surgical incision tracts is sometimes used to prevent malignant seeding, or the spread of cancer cells along an incision.

In general, it’s strongly recommended that patients who are candidates for CRS-HIPEC choose this treatment modality because it offers the best chance of survival. For those whose cancer is not successfully treated by CRS-HIPEC, or whose cancer has progressed after surgery, the next line of treatment is often systemic chemotherapy.

Additional treatment options, like immunotherapy and Tumor Treating Fields, have been FDA-approved for pleural mesothelioma that has recurred after surgery. These modalities are not currently approved for treating peritoneal mesothelioma patients.

However, there are clinical trials that are investigating new treatment options for peritoneal mesothelioma. For patients whose cancer has recurred after CRS-HIPEC, a clinical trial might be an option. Your treatment team can help you weigh the risks and benefits of participation in a trial and determine which trials you would be eligible for.
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