MARS2: Decortication Plus Chemotherapy Associated with Worse Outcomes for Resectable Mesothelioma

Should we consider mesothelioma patients surgical candidates for resection? Are we actually doing more harm than good? 

During the presidential plenary of the IASLC World Conference 2023 on Lung Cancer, Dr. Eric Lim presented the results from the first randomized control trial directly comparing extended pleurectomy decortication versus platinum and pemetrexed chemotherapy alone for the treatment of patients with mesothelioma.  

The MARS 2 (Mesothelioma and Radical Surgery) trial was conducted at a single center in the United Kingdom. A total of 169 patients were randomized to surgery plus chemotherapy and 166 to chemotherapy alone. The patients were followed for a median of 22.4 months.  

One of the hallmark findings of this study was that surgery increased the risk of death in the first 42 months by 28 percent (p=0.03.) Furthermore, there were more adverse events, increased treatment costs, and decreased median survival in the cohort undergoing surgery and chemotherapy.  

This raises the question of why thoracic surgeons should intervene in the treatment of these patients if the outcomes are indeed as above. It may be time for outdated guidelines to be updated as per the evidence base. 

Despite the findings alluding to the retirement of surgical therapy for mesothelioma, the study did not find any difference in the long-term survival between both cohorts. 

However, surgery did lead to a 3.36 times increased risk for adverse events (p<0.001) and reduced EORTC quality of life scores in global health, particularly in global health, physical, social, and role functioning. Patients who underwent surgery also reported worse symptom scores for pain, insomnia, dyspnea, loss of appetite, and financial difficulties. With the median survival of mesothelioma being 12.1 months according to these results, chemotherapy alone may be a more cost-effective and clinically beneficial treatment. 

Dr. Lim stated that changing attitudes so that the disease is considered unresectable would increase access to more effective systemic treatment to improve survival. He did face some scrutiny as the primary outcome of MARS2 was overall survival and with no difference currently reported it may be premature to be rethinking the treatment for such an aggressive thoracic malignancy.