MARS 2: Chemo Outperformed Surgery
The landmark MARS 2 trial found that chemotherapy alone led to better survival than surgery plus chemotherapy for people with pleural mesothelioma.
The MARS 2 trial, published in The Lancet Respiratory Medicine in May 2024, delivered unexpected results that challenge assumptions about the role of surgery in pleural mesothelioma treatment. The landmark Phase 3 study found that patients who received chemotherapy alone survived longer than those who underwent extended pleurectomy decortication (EPD) surgery plus chemotherapy.
The findings have sparked significant debate in the mesothelioma community, with some experts calling for a reconsideration of surgical approaches while others argue the trial’s design limits how broadly its conclusions should be applied.
What MARS 2 Tested
The trial compared two treatment approaches for patients with resectable pleural mesothelioma:
Surgery arm: Extended pleurectomy decortication (EPD) plus platinum-based chemotherapy
Chemotherapy arm: Platinum-based chemotherapy alone
Extended pleurectomy decortication is a lung-sparing surgery that removes the diseased pleura, often along with portions of the diaphragm and pericardium. This was the first randomized controlled trial to evaluate EPD for mesothelioma.
Study Design and Patients
MARS 2 was conducted across 26 hospitals in the United Kingdom between June 2015 and January 2021:
- 1,030 patients assessed for eligibility
- 335 patients randomized (169 to surgery, 166 to chemotherapy)
- 87% were men
- 86% had epithelioid histology (the most favorable cell type)
- Patients received 2 cycles of chemotherapy before randomization
- Median age: approximately 70 years
The Results
The trial’s primary endpoint was restricted mean survival time (RMST) at 2 years. The results favored chemotherapy alone:
Overall Survival:
- Chemotherapy alone: 24.8 months median survival
- Surgery plus chemotherapy: 19.3 months median survival
- Difference in RMST at 2 years: -1.8 months (favoring chemotherapy)
- P value: 0.019 (statistically significant)
Adverse Events:
- Grade 3 or higher adverse events were 3.6 times more common in the surgery group
- Surgery-related complications included respiratory failure, pneumonia, and prolonged hospital stays
Quality of Life:
- Patients in the chemotherapy group reported better quality of life
- Surgery patients experienced more pain, shortness of breath, insomnia, and appetite loss
- Financial difficulties were also worse in the surgery group
Costs:
- Surgery added an average of £14,631 ($20,128) in costs per patient
- This additional expense did not translate to improved outcomes
What This Means
The MARS 2 results challenge the assumption that surgical cytoreduction improves outcomes in mesothelioma. For decades, the mesothelioma community has debated the role of surgery, with some centers advocating aggressive surgical approaches while others have questioned whether the benefits outweigh the risks.
The results point to three key implications. First, not all patients benefit from surgery: for the population studied in MARS 2, extended pleurectomy decortication did not provide a survival benefit and may have caused harm. Second, quality of life matters. Mesothelioma treatment decisions must balance potential survival benefits against the impact on day-to-day life, and in MARS 2 patients both lived longer and felt better without surgery. Third, the trial advances evidence-based decision making by providing the strongest randomized data to date on EPD, giving patients and oncologists a firmer foundation than retrospective series.
MARS 2 studied extended pleurectomy decortication (EPD) specifically. Not all surgical approaches. Some patients with very localized disease may still benefit from surgery. Decisions should be individualized based on disease extent, overall health, and patient preferences. Get a second opinion at a specialized center.
Criticisms and Limitations
The MARS 2 results have not gone unchallenged. Mesothelioma surgeons and researchers have raised four main concerns about the trial design. On patient selection, critics argue that too many patients would fall outside contemporary selection criteria, including older patients, those with comorbidities, and non-epithelioid histology patients who are typically not considered surgical candidates today. On the extent of surgery, some surgeons question whether routinely resecting the diaphragm (as done in EPD) was necessary for all patients, and suggest that less extensive surgery might have achieved similar tumor removal with fewer complications. On timing, critics note that patients may have been operated on too late in the disease process because staging practices did not fully identify all disease extent. On the evolution of treatment, the trial began in 2015, before checkpoint inhibitors were approved for mesothelioma, and modern surgical programs now integrate immunotherapy in ways that could affect outcomes.
Expert Perspectives
The accompanying Lancet editorial acknowledged the trial’s importance while noting its limitations:
“Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma had never been evaluated in a randomised trial. MARS 2 provides important evidence that should inform clinical practice, though the debate about the role of surgery in mesothelioma is far from over.”
Researchers advocating for surgery argue that highly selected patients at high-volume centers may still benefit, even if the average patient in a broad trial does not.
What Patients Should Know
For newly diagnosed patients:
- Discuss the MARS 2 results with your medical team
- Ask whether surgery is being recommended and why
- Understand that surgery is not necessarily the right choice for everyone
- Consider a second opinion at a specialized mesothelioma center
Questions to ask:
- Am I a candidate for surgery based on current selection criteria?
- How does my case compare to the patients in MARS 2?
- What is my surgeon’s experience with mesothelioma surgery?
- What quality of life can I expect with each treatment option?
- How would immunotherapy factor into my treatment plan?
Important context:
- MARS 2 studied extended pleurectomy decortication specifically, not all surgical approaches
- Some patients with very localized disease may still be appropriate surgical candidates
- Decisions should be individualized based on disease extent, overall health, and patient preferences
The Bigger Picture
The MARS 2 trial represents an important step toward evidence-based treatment of mesothelioma. For too long, treatment decisions have been based on retrospective data and individual center experience rather than randomized trials.
The negative result does not mean surgery has no role in mesothelioma, but it does suggest that the aggressive surgical approaches used in the past may have harmed more patients than they helped. Future research will need to identify which specific patients, if any, truly benefit from surgical intervention.
The evolution of mesothelioma treatment continues, with immunotherapy now standard in first-line treatment. How surgery integrates with modern systemic therapies remains an open question that future trials may help answer.
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Reader Q&A
Frequently Asked Questions
What did MARS 2 find?
Patients who received chemotherapy alone survived longer (24.8 months) than those who had extended pleurectomy decortication surgery plus chemotherapy (19.3 months). Surgery patients also had 3.6x more serious adverse events, worse quality of life, and an additional ~$20,000 in costs.
Does this mean no mesothelioma patient should have surgery?
Not necessarily. MARS 2 studied extended pleurectomy decortication specifically. Some surgeons argue that highly selected patients at high-volume centers may still benefit. The trial began before immunotherapy approval, and modern programs integrate immunotherapy differently. Get a second opinion at a specialized center.
What were the criticisms of the trial?
Critics argued that too many patients fell outside contemporary selection criteria (older patients, comorbidities, non-epithelioid histology). Some questioned whether the extensive surgery performed was necessary for all patients, and whether immunotherapy integration would change outcomes.
What questions should I ask my doctor?
Am I a candidate for surgery based on current selection criteria? How does my case compare to MARS 2 patients? What is my surgeon’s mesothelioma experience? What quality of life can I expect with each option? How would immunotherapy factor into my treatment plan?
Why does the Mars2 trial not mean the end of all mesothelioma surgery?
The MARS2 trial found that chemotherapy alone produced longer median survival (24.8 months) than chemotherapy plus extended pleurectomy/decortication surgery (19.3 months), leading some to conclude surgery should be abandoned. However, trial investigators and other surgeons have identified significant limitations in patient selection that question whether these findings apply to all people with mesothelioma. Post hoc analysis suggests only about one in three surgical patients would have met current selection criteria for early-stage epithelioid mesothelioma, and the trial included patients with poor prognostic factors, advanced disease, and tumor types (sarcomatoid and biphasic) less likely to benefit from surgery. A 2026 study of carefully selected patients found P/D surgery had no in-hospital deaths and a 90-day mortality rate of just 4.2%, suggesting outcomes improve substantially with strict patient selection and experienced centers. Researchers argue that a future trial focusing specifically on early-stage epithelioid mesothelioma with contemporary selection criteria remains justified.
Is stage 2 mesothelioma curable?
No stage of mesothelioma, including stage 2, is considered curable. People with stage 2 mesothelioma have a 1-year survival rate of 70-86% depending on pleural or peritoneal type, with some achieving remission or long-term survival through aggressive treatments like surgery. Treatments aim to shrink tumors, extend life expectancy (up to 19 months on average with surgery), and improve quality of life, but cancer recurrence remains common.
What is the best hospital for mesothelioma treatment?
University of Texas MD Anderson Cancer Center ranks No. 1 in the U.S. for cancer treatment in 2025, for the fifth consecutive year, and treats more people with mesothelioma than nearly any other center. Other highly ranked hospitals for pleural mesothelioma include Brigham and Women’s Hospital and Massachusetts General Hospital, while Mayo Clinic-Rochester leads for peritoneal mesothelioma. People with mesothelioma receive care at these centers, which offer multidisciplinary teams and access to clinical trials. Rankings from U.S. News & World Report reflect factors like patient outcomes and expertise volume.
How did Steve McQueen get mesothelioma?
Steve McQueen was exposed to asbestos through multiple occupational and military sources over several decades. His primary exposure occurred during his service in the U.S. Marine Corps from 1947 to 1950, when he worked aboard naval ships and in shipyards, including removing asbestos lagging from pipes at Camp Lejeune. After his military service, he encountered additional asbestos exposure on movie soundstages where insulation contained the mineral, while wearing flame-resistant racing suits made with asbestos, and while working on race car and motorcycle brakes. McQueen did not develop symptoms until 1978, nearly 30 years after his initial military exposure, reflecting the typical latency period of 20 to 50 years between asbestos exposure and mesothelioma diagnosis. He was diagnosed with pleural mesothelioma in December 1979 and died in November 1980 at age 50.