The Rise of Multimodal Therapy

When most people are fighting an illness and learn their current treatment isn’t working, they try another therapy or seek a second opinion. Sometimes it takes several tries before doctors can pinpoint the most effective treatment, and the fastest way to obtain it often starts with finding a qualified specialist.

The same applies for mesothelioma patients, a group whose struggle with ineffective treatments can be especially difficult. Not every patient is healthy enough to qualify for the leading curative therapies, and it’s rare for any single treatment to extend life expectancy beyond the cancer’s average survival rate of one year.

In every case, timely treatment is critical.

The many challenges of fighting mesothelioma have troubled patients and doctors for decades, but we now understand the disease better than ever before. Knowledge of how mesothelioma behaves on a molecular level has allowed doctors to personalize treatments for each patient, improving their effectiveness. The standard approach to therapy has evolved over time, and leading medical centers now offer treatment plans that have helped patients beat their initial prognosis.

After years of trial and error, experts discovered the best chance of long-term survival comes from combining treatments — not trying therapies one after the next until the patient responds. Doctors call this combined treatment strategy multimodality, or multimodal therapy.

Multimodal therapy is a unique approach that combines multiple therapies into the course of treatment. Unless your overall health or the stage of your cancer excludes you from aggressive treatment options, this approach will likely provide the most promising chance of extending survival.

One of the most effective and widely used treatment plans for pleural mesothelioma is called trimodality therapy, a multimodal approach that combines surgery, chemotherapy and radiation therapy.

Before multimodality rose to the forefront of mesothelioma treatment, therapy was far less effective. No single treatment could significantly improve survival, and bimodality therapy using two types of treatment also failed to produce satisfactory results.

At the turn of the 20th century, practically no effective cancer treatments existed besides surgery. Radiation therapy and surgery were the mainstays of cancer treatment until the 1960s, when researchers began noticing that cure rates did not improve as they explored increasingly aggressive local treatments. The problem was the standard treatment approach of the time did not address micrometastasis — a complex process that causes cancer cells to spread from their site of origin and form distant tumors too small for doctors to detect.

When new data revealed that multi-drug chemotherapy regimens could fight micrometastasis and cure various cancers, doctors began introducing chemotherapy as a complement to surgery and radiation therapy. Multimodality was first proven effective in breast cancer patients, but doctors soon applied the concept to various other cancers.

In 1980, Brigham and Women’s Hospital and the Dana-Farber Cancer Institute in Boston collaborated on one of the first long-term studies on multimodal therapy for pleural mesothelioma.

Encouraged by the positive outcomes of early-stage lung cancer patients treated with chemotherapy before surgery, the researchers believed a multimodal technique could improve survival for mesothelioma patients as well. For the next 15 years, they recorded the outcomes of 120 patients who received trimodality therapy. The treatment plan started with EPP surgery followed by adjuvant chemotherapy and radiation therapy.

The study results concluded that trimodality is an appropriate and effective treatment plan, especially for patients diagnosed in the three earliest stages of disease. Patients with stage I cancer survived an average of 22 months, compared to 17 months for stage II and 11 months for stage III. The best survival, however, occurred in early-stage patients with no lymph node involvement and the epithelial cell type of disease.

Although the Boston researchers confirmed that a multimodal approach is most effective, to this day we have yet to uncover the optimal approach to treatment.

Following the success of this groundbreaking study, researchers designed more clinical trials centered on improving the standard approach to care. These studies mainly pursued ways to diagnose the disease earlier, extend survival further and help patients achieve a better quality of life.

Another key focus was balancing maximal delivery of therapy with patient safety. In the early years of mesothelioma research, nearly every trimodality study involved extrapleural pneumonectomy surgery. While experts historically believed EPP was the most effective potentially curative surgery, recent investigations revealed high rates of death and complications.

In an influential 2008 study, three leading treatment centers reported the results of 663 pleural patients who underwent EPP or pleurectomy/decortication (P/D), a less aggressive surgery that spares the diseased lung. After 16 years of follow up, researchers noticed better survival and lower death and complication rates among P/D patients.

These findings had a dramatic effect on surgical practice. Surgeons have performed much fewer EPP procedures since the study’s publication. However, the results aren’t conclusive, and experts continue to debate which surgery is best. For example, the rate of cancer recurrence remains higher with P/D, despite longer overall survival. The operation you receive will depend on your unique clinical situation, including the stage of your cancer.

Mesothelioma experts have spent decades analyzing research on the most promising approaches to treatment. The most reliable studies have helped doctors shape the standard of care, and treatment strategies are always progressing.

Currently, most stage 1-4 pleural mesothelioma patients receive surgery as a main treatment, followed by adjuvant chemotherapy, radiation therapy or both. The surgery aims to remove the bulk of the cancer growth, while the adjuvant therapies help prevent the cancer from returning. Stage IV patients, and those whose cancer has returned, typically will not benefit from surgery. Instead, doctors suggest chemotherapy or supportive care to improve symptoms.

Surgery can be effective for peritoneal patients, but only when the cancer is confined to the abdomen. Radiation therapy is rarely offered for this diagnosis, but doctors often combine surgery with adjuvant chemotherapy to improve survival and prevent recurrences.

Hyperthermic intraperitoneal chemotherapy, in which doctors administer chemotherapy directly to the abdomen after surgery, is an effective technique that is becoming increasingly popular. HIPEC given immediately after surgery has provided some of the most hopeful patient outcomes to date.

In coming years, researchers will continue to investigate and refine the best available treatments. Future clinical trials will provide valuable information about how doctors can best deliver treatment. The past has shown that survival is best with multimodal treatment, and future studies will strive to uncover the treatments, timing and doses that help patients achieve the longest survival and best quality of life.