Multimodal therapy for mesothelioma is a combination of two or more cancer treatments. A common combination is surgery with chemotherapy, radiation, or both. Multimodal therapy is currently considered to be the best treatment approach for mesothelioma.[1]
What Is Multimodal Therapy?
Multimodal therapy refers to a care strategy that involves multiple treatment types. Instead of just one technique, like chemotherapy, treatment teams attack the cancer on multiple fronts.
What Is the Best Treatment for Mesothelioma?
The best treatment for mesothelioma varies by patient. The standard treatments used for multimodal therapy for mesothelioma are chemotherapy, surgery, and radiation therapy.
How Do Oncologists Choose Treatments for Mesothelioma Patients?
Treatment teams look at a patient’s health, cancer stage and location, and other factors to determine the best combination of treatments. For most people, multimodal treatment is more effective and offers a better prognosis than a single treatment alone.
What Is the Latest Treatment for Mesothelioma?
Surgery, chemotherapy, and radiation therapy are the three most common and standard therapies, but researchers are working on better, safer treatments.
These may become part of a patient’s multimodal treatment plan and include immunotherapy, targeted therapy, tumor treating fields, and photodynamic therapy.
What Are the Benefits of Multimodal Therapy for Mesothelioma?
The primary advantage of using multimodality is that it gives most patients a better outcome. The median survival rate for untreated mesothelioma is just six to nine months.
Any treatment extends this, but the patients living the longest receive multimodal treatment, according to several studies:[2]
- A study with 21 patients receiving both chemotherapy and surgery recorded an overall median survival time of nearly 26 months.
- Another study looked at trimodality involving radiation, chemotherapy, and surgeons. The overall median survival time for these patients was 39.4 months.
- A randomized controlled trial of multimodal treatment compared two groups of mesothelioma patients receiving two or three types of treatment. Each group underwent radical surgery and chemotherapy, but only one group also received radiation therapy. The survival time was about the same for each group.
Studies like these generally show that multimodal treatment extends patients’ lives. However, adding more treatments is not always better.
What Do the Official Treatment Guidelines Say About Multimodal Therapy?
Several organizations, including the National Comprehensive Cancer Network, issue regularly updated guidelines for treatment based on research:[3]
- Chemotherapy can be used alone in patients who do not qualify for surgery and in combination with surgery for those who are good candidates.
- Some patients may receive chemotherapy combined with an antiangiogenesis drug.
- Radiation therapy is not recommended as a sole treatment but can be used as part of a multimodal plan.
The Standard Multimodal Therapies for Mesothelioma
The three most common treatment strategies for cancer are often used in combinations of two or three. Treating mesothelioma with two or more approaches generally has better outcomes, such as extended survival times.[1] The actual choice of treatments depends on multiple individual factors.
- Chemotherapy: Chemotherapy is a treatment that circulates drugs throughout the body or in a specific part of the body. They target and kill fast-growing cells, like cancers. Healthy cells can also be affected, which leads to serious side effects. Researchers are always looking for more targeted drugs that cause minimal damage to healthy cells.
- Surgery: Surgery remains one of the best and most effective ways to treat early-stage mesothelioma. Most advanced patients are not good candidates for surgery because of the inability to remove all of the cancerous tissue. Surgery for pleural and peritoneal mesothelioma is often highly invasive. An extrapleural pneumonectomy, for instance, involves removing an entire lung, the pleura, lymph nodes, and part of the diaphragm.[4]
- Radiation therapy: High-energy beams of radiation are used to target and kill cancer cells with radiation therapy. This is most often delivered externally, with a machine that aims the beam at a specific part of the body with cancer. Brachytherapy is administered internally, using a small device placed inside the body to target the tumor with radiation. Radiation therapy effectively kills cancer cells but can also cause damage to healthy tissues. Advances in this treatment are helping doctors give higher doses of radiation that are better targeted at tumors.[5]
Multimodality in Peritoneal Mesothelioma
Patients with peritoneal mesothelioma also generally receive multimodal treatment. One of the most effective combinations is cytoreductive surgery to remove the bulk of tumors followed by HIPEC.
HIPEC stands for heated intraperitoneal chemotherapy. It differs from systemic chemotherapy in that it is targeted to the abdomen. After removing tumors during surgery, doctors circulate heated chemotherapy drugs throughout the abdominal cavity.
What Are the Side Effects of Multimodal Treatment?
Side effects are inevitable with cancer treatment. They vary by individual and the types of therapies used. Chemotherapy can cause a whole host of side effects, including:
- Nausea and vomiting
- Hair loss
- Fatigue
- Mouth sores
- Changes in taste and appetite
- Lowered immunity
- Increased illness
- Pain
Surgery is also risky and can cause side effects and complications. The more extensive the surgery, the bigger the risks. Some of the potential complications of mesothelioma surgery include:
- Excessive bleeding
- Blood clots
- Infection
- Damaged organs
- Lung collapse
- Respiratory issues
- Pneumonia
Radiation usually causes fewer side effects. Most commonly people experience fatigue and skin rashes. Hair loss might also occur at the application sites.
Combining treatments with a multimodal approach doesn’t necessarily increase the risk of side effects. However, when patients undergo multiple treatments, the combination of side effects might be too much to continue. These treatments are only effective if the patient is able to complete them all.
Advances in Mesothelioma Multimodal Treatment
Chemotherapy, surgery, and radiation remain the standard therapies for mesothelioma. Researchers continue to study other therapies and innovative treatments that can be added to the traditional multimodality.
Intensity-Modulated Radiation Therapy (IMRT)
Radiation therapy is an important adjuvant to surgery, especially with new advances that allow doctors to target tumors better and avoid harming healthy tissue.
In one study, researchers found that patients may have better survival outcomes when one of these advanced types of radiation, called IMRT, was used right after surgery. IMRT follows the shapes of tumors for more targeted treatment.[6]
Targeted Chemotherapy
In a mouse model study, researchers used nanoparticles loaded with chemotherapy drugs to target tumor receptors better. The study results suggested that using this strategy along with surgery could prolong survival times for mesothelioma patients.[7]
Immunotherapy
An emerging type of treatment may add to the effectiveness of multimodal treatment in the future. Immunotherapy uses the patient’s immune system to attack and kill cancer cells. Studies have shown that including immunotherapy can be tolerated by mesothelioma patients and extends survival times.[8]
In 2020, the immunotherapy combination of nivolumab with ipilimumab became the first new medication approved for treating mesothelioma in years. Clinical trials with the combination resulted in better overall survival than treatment with chemotherapy.
Antiangiogenesis
The drug bevacizumab (Avastin) is an antiangiogenesis medication. It disrupts a tumor’s ability to create new blood vessels. This results in less blood flow to the tumor and slowed or halted growth. Official guidelines now recommend using bevacizumab in combination with chemotherapy for many patients.
Four-Modality Treatment
While many patients receive two or three treatments, a four-modality approach may be appropriate for some. This usually means using the three standard therapies of surgery, radiation, and chemotherapy as well as immunotherapy.
Studies have found that the combination of four different treatments is both tolerable to most patients and beneficial in terms of survival.[9]
Tumor Treating Fields
Tumor Treating Fields, or TTFields, is a newly approved medical device for treating mesothelioma. It uses electric fields at low intensity to kill cancer cells. The device is applied outside the body and is non-invasive.
As such a new treatment device, research is limited, especially as a part of multimodality. In clinical trials, researchers used TTFields along with chemotherapy in mesothelioma patients. The median survival time was over 18 months.[10]
Photodynamic Therapy
Photodynamic therapy is an emerging cancer treatment that uses light to activate targeted anti-tumor drugs. It is a type of targeted treatment that is more precise than systemic chemotherapy.
A study of patients undergoing lung-sparing surgery included photodynamic therapy after the procedure. Chemotherapy often cleans up remaining cancer cells after surgery, but photodynamic therapy may cause fewer side effects.
Researchers found that this combination of surgery and photodynamic therapy improved median survival time. They saw the best results for patients with epithelioid mesothelioma, a cell type that is easier to treat.[11]
The SMART Protocol for Mesothelioma
A recently developed multimodal protocol for pleural mesothelioma has had promising results. Surgery for Mesothelioma After Radiation Therapy, or SMART, changes the usual order of therapies.
The radiation therapy shrinks and manages the edges of tumors before surgery. It also eliminates some of the problems associated with using chemotherapy before surgery, like side effects. Chemotherapy also takes more time that mesothelioma patients don’t have.
Studies have found that SMART can extend median survival time in pleural mesothelioma past the five-year mark, a result rarely seen with other treatment types.[12]
How Do Treatment Teams Choose Multimodal Therapies?
There is no single, standard way to administer these treatments in a multimodal approach for every patient. The treatments used and the order in which they are used depend on many factors:
- Age
- Overall health
- Tumor location and cell type
- The stage of the cancer and metastasis
- Patient preference
The Order of Multimodal Treatments
Therapies used in a multimodal approach are labeled as neoadjuvant, primary, or adjuvant, which describes when and why they are used:[13]
- Neoadjuvant therapies are used before a primary treatment to make that main therapy easier or more successful. For instance, chemotherapy may be used first to shrink tumors so that the primary treatment, surgery, is less extensive and invasive.
- The primary treatment is the main therapy, which is hoped will provide the best outcomes in slowing or stopping tumor growth. In mesothelioma, this is usually surgery or chemotherapy.
- Adjuvant therapy is used after the primary treatment to minimize the risk of recurrence or to slow the progression. Radiation may be used after surgery to eliminate any remaining cancer cells, for example.
Who Is Eligible for Multimodal Treatment?
Eligibility for any treatment for mesothelioma depends on individual patient characteristics:
- The stage of mesothelioma
- The patient’s age and overall health
- Tumor location
- Cancer cell type
- The patient’s preferences and goal
Many patients with mesothelioma qualify for at least two types of treatment, but not necessarily all types. For instance, patients with advanced mesothelioma likely cannot have surgery, but they might benefit from a combination of chemotherapy and immunotherapy.
Talk to Your Doctor About Multimodal Treatment
Multimodal therapy for mesothelioma is now standard practice for most patients. Whether these strategies are used and in what order depends on the patient. Talk to your doctor about all of your treatment options.
