A new UK study challenges the standard treatment for malignant pleural mesothelioma, suggesting that chemotherapy alone may be more effective than surgery combined with chemotherapy. Historically, maximal surgical cytoreduction with chemotherapy has been the norm, aiming to improve survival by removing as many tumors as possible.
The Practice-Changing MARS 2 Trial
The MARS 2 trial, a randomized study across 26 centers, tested this surgical approach. 335 patients with resectable pleural mesothelioma were assigned to extended pleurectomy/decortication followed by chemotherapy (169 patients) or chemotherapy alone (166 patients).
Contrary to expectations, patients receiving only chemotherapy had longer median survival (24.8 months) compared to those undergoing surgery plus chemotherapy (19.3 months). This survival advantage was consistent across various analyses and subgroups.
Worse Survival with Surgery
The restricted mean survival time (RMST) analysis showed a significant survival benefit for chemotherapy alone, particularly in the non-epithelioid subgroup. Surgery was associated with higher rates of serious adverse events and poorer quality of life.
Increased Risks, No Benefit from Surgery
Surgery resulted in 3.6 times more serious adverse events compared to chemotherapy alone, and economic analyses found it to be not cost-effective at any willingness-to-pay threshold.
Dr. Eric Lim, the lead author, noted, “Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone.”
Balanced and Robust Trial
The trial’s strengths include balanced baseline characteristics and consistent results across the study period, mitigating potential reporting bias despite the unblinded design.
Paradigm Shift and Practice Implications
The MARS 2 results suggest chemotherapy alone may be preferable to aggressive surgery for many mesothelioma patients. Treatment guidelines may shift, limiting surgery’s role to clinical trials.
As the authors concluded, “Extended pleurectomy decortication and chemotherapy were associated with worse survival, more serious adverse events, poorer quality of life, and higher costs compared with chemotherapy alone.”
By emphasizing the superiority of chemotherapy alone in terms of survival, adverse events, and cost-effectiveness, the MARS 2 trial provides compelling evidence for reevaluating the role of surgery in treating mesothelioma.
