MARS2 Study Author Proposes Eliminating Surgery for Pleural Mesothelioma

A ceiling sign in a hospital hallway points one direction for chemotherapy and another direction for surgery, symbolizing the quandary posed by the study covered in this post.

In mid-September, researchers presented highly anticipated results from the MARS2 clinical trial. The study compared survival for two groups of pleural mesothelioma patients: one group had chemotherapy with surgery, and the other had chemo without surgery. The results showed no significant difference in survival time between the two groups.

Upon reviewing the data, at least one author came to a surprising conclusion. In discussions about the study, London-based lead author Dr. Eric Lim voiced support for eliminating surgery for this rare cancer. Doing so would extend survival by 28%, according to his analysis. But flaws in the study structure have led to questions about Lim’s findings.

“Classifying this disease as [inoperable] from the outset would increase access to more effective systemic treatments to improve survival for patients with other stages of disease.”

– Eric Lim, MD, Thoracic Surgeon

American Surgeon Questions Study Analysis

Dr. Lim shared the study results with attendees of the 2023 World Conference on Lung Cancer. Among them was United States-based surgeon Paula A. Ugalde Figueroa, MD. She posed several important questions about Lim’s data and analysis.

MARS2 Study at a Glance

  • Location: The United Kingdom
  • Patients: 335 pleural mesothelioma patients, all eligible for surgery
  • Treatments: Chemotherapy with or without pleurectomy surgery
  • Median survival results
    • Chemo: 24.8 months
    • Chemo + surgery: 19.3 months

Key issues raised in Ugalde Figueroa’s commentary included:

  • No true survival difference between groups: Median survivals differed between the two groups, but not significantly. Though the survival numbers look different, statistical testing indicates they are not.
  • Patient characteristics were unequal between groups: The surgery group had a higher percentage of patients with significant risk factors. Of surgery patients, 83% had tumors that extended into their lungs compared to just 50% of the other group. This means the surgery group may have been more at risk of surgical complications.
  • Treating hospitals lacked experience: Nearly half of the surgery patients underwent treatment at low-volume centers. This could mean those centers did not have enough experience managing surgical complications.

Dr. Lim responded to the last point, saying all but one of the study locations are national centers of surgical excellence for mesothelioma. It is unclear whether that status has anything to do with surgical volume.

And research indicates patient volume does affect treatment outcomes. Centers with less experience tend to have higher complication and mortality rates. So Dr. Ugalde Figueroa’s question may reflect many mesothelioma doctors‘ thoughts on this study.

“Would the outcome be different in exclusively high-volume centers?”

– Paula A. Ugalde Figueroa, MD, Thoracic Surgeon

Cell Types Were Not Balanced Between Groups

Dr. Ugalde Figueroa made important points about this study. But one other issue may have affected survival outcomes. The surgery group included about 2.6 times as many sarcomatoid patients as the chemo group.

Sarcomatoid tumors treated with chemo generally have significantly worse survival than other cell types. If one group had twice as many sarcomatoid patients, that factor alone might bring down the median survival.

Mesothelioma Survivor Points Out Cross-Pond Differences

We asked pleural mesothelioma survivor Heather Von St. James about Dr. Lim’s proposal. As someone who underwent aggressive surgery-based treatment, she had some thoughts.

“There has long been an agreement [between Americans and Brits] to disagree about the role of surgery for pleural mesothelioma,” she said. According to Heather, American mesothelioma specialists tend to value surgery, and their British counterparts do not. Her assertion lines up well with the interaction between Dr. Lim and Dr. Ugalde Figueroa.

What Does It Mean for Mesothelioma Patients?

The MARS2 trial is just one study with debatable results. So it is too soon to tell how this research may affect patients. For now, medical literature supports surgery-based treatment for operable cases of mesothelioma. Given the volume of studies that take this stance, it seems unlikely to change any time soon.