A Perspective on the MARS2 Trial.

Introduction: The phase 3 randomized controlled trial of extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (PM) (MARS2) reported "extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable PM, compared with chemotherapy alone." These results have led to considerable discourse regarding the future role of surgery for PM, and there has not been unanimity in the mesothelioma surgical community regarding the trial interpretation. This "perspective" evaluates MARS2 using internationally renowned PM experts who either agreed with the trial interpretation or who found issues with its conduct which may have influenced the results.

Methods: A facilitator (HP) worked with team leaders (GW, IO) to assemble individuals offering opinions regarding the trial and its conclusions. Arguments agreeing or not agreeing with the trial interpretation were written only after publication of the full trial. Once both arguments were received by the facilitator, the individual team manuscripts were combined and sent to each team allowing editing for changes in perceived factual errors.

Findings: Insightful arguments include (but were not limited to) the difficulties yet advantages of randomization, quality assurance, selection of histologic subtypes, the timing of randomization, use of preoperative staging, statistical methods, and reasons for surgical mortality.

Conclusions: The decision to operate for PM in the future will continue to be defined by consensus guidelines and health payer willingness, and the interpretation of MARS2 may play an important role in modulating the role of surgery in the future.