Key Takeaways
- The MARS2 clinical trial was a landmark UK study (2015–2020) that compared chemotherapy alone versus chemotherapy combined with extended pleurectomy decortication (EPD) surgery for mesothelioma patients.
- The results were surprising: patients who received chemotherapy alone had a median survival of 24.8 months, compared to 19.3 months for patients who received both chemotherapy and EPD surgery. The surgery group fared worse.
- This contradicted the researchers’ own hypothesis — and the general assumption that multimodal treatments (combining therapies) always outperform single treatments.
- The findings suggest that even when surgery successfully removes all visible cancerous tissue, the physical trauma of such an extensive operation can outweigh the benefits — particularly for older patients or those in poor physical condition.
- MARS2 has important implications: clinicians must weigh the benefits versus risks of each treatment and consider the whole patient — age, physical fitness, mental capacity — before recommending aggressive surgical approaches.
- Multimodal treatment remains effective in many cases, but MARS2 demonstrates that context matters — the right treatment depends on the individual patient, not just the disease.
MARS2 Clinical Trial
Chemotherapy has been the main avenue for mesothelioma care, up until recently. It’s effective because it’s a systemic treatment, meaning that it impacts the growth of all bodily cells. This sweeping approach is useful for mesothelioma, as only a few mesothelioma cells can become full-scale tumors. Treatments that target the bulks of mesothelioma tumors aren’t as effective, as these treatments often leave trace amounts of the tumors. These treatments, although curative in intent, usually don’t work well in the context of mesothelioma.
The MARS2 clinical trial has sought to look at the efficacy of chemotherapy in conjunction with surgery, and is the first trial of its kind. The surgery used is called “extended pleurectomy decortication,” (EPD) in which both layers of the pleural membrane are removed, as well as afflicted areas of the diaphragm, lungs, and heart. This tissue is replaced with either artificial tissue or a graft of similar tissue. Given the breadth of surgical removal and replacement, the procedure is intensive and not usually recommended. However, because it (in theory) removes all of the cancerous tissue, it’s clinically acceptable and sometimes encouraged, especially in cases of high patient fitness.
MARS2 trials took place in the UK from 2015-2020, and the trial has recently entered phase III (meaning it’s in the last phase of testing). During the trial itself, the experimental group received EPD and chemotherapy, while the control group received only chemotherapy. The results from the trial were somewhat surprising: even the researchers hypothesized the experimental group would experience higher overall survival rates. Even though multimodal approaches are almost always more effective than singular approaches, the MARS2 trial was an exception. Patients that received only chemotherapy—so, the current standard of mesothelioma treatment—had a median overall survival rate of 24.8 months, compared to the experimental group’s 19.3 months.
These findings are interesting for several reasons. One, the results didn’t align with the researchers’ hypotheses, which means that not all treatment options—despite theoretical efficacy—could work like they’re thought to work. Even though the EPD likely removed all of the mesothelial tissue, which would mitigate recurrence, metastasis, and further treatment, patients’ bodies couldn’t recover from the trauma of such a severe surgery.
Implications for Future Care
Like previously mentioned, multimodal approaches are almost always more effective than other routes of treatment. Two or more treatment models act as safety nets, usually target different systems/pathways associated with mesothelioma, and mitigate the multifaceted risks of mesothelioma. However, MARS2 has elucidated an important fact: clinicians need to weigh the benefits vs. the risks of treatment models, and they must consider the age/physical fitness of patients prior to recommending treatment. These findings lend themselves towards a more holistic and contextual treatment model for mesothelioma, in which the entire person—mental capacity, physical standing, etc.—is considered before strides in treatment are made. For instance, if a young male (<45 years old) is diagnosed with mesothelioma—which would be rare—he might be better suited to EPD than chemotherapy. The inverse is likely true for someone older than our hypothetical male. Context matters, especially when treatments are life-altering.
If you or a loved one has been diagnosed with mesothelioma or another asbestos-related disease, we are here to help. Our website offers useful information regarding types of asbestos-related diseases, hospitals to receive treatment in Pennsylvania, a variety of different treatment options, and more. For more information or for legal help, please call us at (800) 505-6000 or simply fill out our contact form.
Frequently Asked Questions
What was the MARS2 clinical trial?
MARS2 was a randomized clinical trial conducted in the UK from 2015 to 2020 that tested whether adding surgery to chemotherapy improved outcomes for mesothelioma patients. The experimental group received chemotherapy plus extended pleurectomy decortication (EPD) — a major surgery that removes both layers of the pleural membrane, plus affected areas of the diaphragm, lungs, and heart. The control group received chemotherapy alone. The trial has recently entered phase III (the final phase of testing).
What is extended pleurectomy decortication (EPD)?
EPD is an extensive surgery in which both layers of the pleural membrane are removed, along with affected portions of the diaphragm, lungs, and heart lining. The removed tissue is replaced with either artificial material or tissue grafts. Because of the breadth of what is removed and replaced, EPD is one of the most intensive surgical procedures available for mesothelioma — and is generally only recommended for patients in relatively good physical condition.
What did the MARS2 trial find?
The results surprised the researchers. Patients in the chemotherapy-only group had a median survival of 24.8 months, while patients who received chemotherapy plus EPD surgery had a median survival of 19.3 months. The group that underwent the additional surgery actually lived 5.5 months shorter on average. This contradicted the hypothesis that adding surgery would improve outcomes — and challenged the general assumption that multimodal approaches always outperform single-treatment approaches.
Why did surgery make outcomes worse?
The researchers believe the answer lies in the physical trauma of such an extensive procedure. Even though EPD may successfully remove all visible cancerous tissue, the surgery itself — which involves removing and replacing portions of the pleural membrane, diaphragm, lungs, and heart lining — is extremely demanding on the body. For many patients, particularly older patients or those with compromised health, the recovery toll may have outweighed the cancer-removal benefit.
Does this mean surgery should never be used for mesothelioma?
No. The MARS2 findings don’t eliminate surgery as a treatment option — they highlight that patient selection is critical. For a younger, physically fit patient, EPD may still offer benefits that outweigh the surgical risks. For an older patient or one in poor physical condition, chemotherapy alone may be the better path. The key takeaway is that treatment decisions should be individualized — considering the patient’s age, fitness level, disease stage, and overall health — rather than defaulting to the most aggressive option available.
How does MARS2 change the approach to mesothelioma treatment?
MARS2 reinforces the importance of a holistic, patient-centered treatment model. Rather than assuming that more treatment is always better, clinicians should weigh the specific benefits and risks of each approach for each individual patient. This includes evaluating not just the cancer itself but the whole person — physical fitness, mental health, age, and recovery capacity. The trial also highlights the ongoing importance of clinical research in challenging established assumptions about mesothelioma care.
What should I do if I’ve been diagnosed with mesothelioma?
If you or a loved one has been diagnosed with mesothelioma, understanding the full range of treatment options — and which ones are most appropriate for your specific situation — is an important step. Clinical trials like MARS2 help inform these decisions. For information about your legal options, call (800) 505-6000 or fill out our contact form for a free consultation.
