Dr Wolf on Challenges Conducting Clinical Trials Evaluating Surgery in Mesothelioma

Andrea Wolf, MD, MPH, director , New York Mesothelioma Program, Icahn School of Medicine, Mount Sinai, discusses common challenges experienced when conducting randomized controlled trials to assess the role of surgery in mesothelioma management, including issues related to standardizing surgical procedures and pathology interpretations.

Wolf begins by emphasizing the achievements of the interventional MARS2 trial (NCT02040272). Following 2 cycles of chemotherapy, 328 patients were randomly assigned to receive extended pleurectomy decortication surgery in addition to chemotherapy vs chemotherapy alone. The study evaluated outcomes such as overall survival, cost-effectiveness, and quality of life.

Despite the MARS2 trial's success in randomly assigning patients to surgery, Wolf states that limitations arise in standardizing the surgical operation itself. Variations in surgical techniques and the extent of resection can lead to inconsistent outcomes, making it difficult to assess the true impact of surgery on patient survival and disease control, she explains.

Standardizing pathology interpretations in mesothelioma trials is also a challenge, Wolf continues, adding that this is particularly evident with blood and tissue samples. The assessment of microscopic disease adds complexity to standardization, as many clinicians believe that this result cannot be consistently reported within this patient population. This variability in pathological evaluations complicates efforts to draw definitive conclusions regarding the benefits of surgery from randomized clinical trials, she explains.

To address these limitations, international collaboration is critical, Wolf emphasizes. Efforts are underway to standardize treatment protocols and pathology assessments through collaborative networks such as the International Association for the Study of Lung Cancer (IASLC), she details. These collaborations aim to refine prognostic factors and staging criteria, ultimately helping to identify which patients are most likely to benefit from surgery, Wolf explains.

In the future, mesothelioma treatment will likely involve a combination of surgery and personalized adjuvant therapies, tailored based on biomarkers and tissue characteristics obtained from surgical specimens, Wolf concludes.