MARS 2 Trial: the Future of Pleurectomy Decortication in Pleural Mesothelioma

In The Lancet Respiratory Medicine, Eric Lim and colleagues 1 Lim E Waller D Lau K et al. Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial. Lancet Respir Med. 2024; (published online May 10.)https://doi.org/10.1016/S2213-2600(24)00119-X PubMed Google Scholar present results of the MARS 2 trial, which sought to answer the question of whether (extended) pleurectomy decortication has an effect on survival and quality of life of patients with resectable pleural mesothelioma. The principal evidence for surgery before the MARS 2 trial was retrospective case series, and no controlled trials were available. The trial has a randomised, pragmatic design and the control group is chemotherapy alone. Surprisingly, results showed superior overall survival in the chemotherapy alone group (24·8 months vs 19·3 months) and the surgery group had worse quality of life, a higher proportion of adverse events, and higher costs. Although these results should be considered relevant for clinical practice—discouraging surgery outside controlled settings of clinical studies or multidisciplinary defined therapeutic strategies in specialised centres—we do not think that the results of this trial alone answer the question it posed. Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trialExtended 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. Full-Text PDF Open AccessLeveraging the pleural space for anticancer therapies in pleural mesotheliomaMost patients with pleural mesothelioma (PM) present with symptomatic pleural effusion. In some patients, PM is only detectable on the pleural surfaces, providing a strong rationale for intrapleural anticancer therapy. In modern prospective studies involving expert radiological staging and specialist multidisciplinary teams, the population incidence of stage I PM (an approximate surrogate of pleura-only PM) is higher than in historical retrospective series. In this Viewpoint, we advocate for the expansion of intrapleural trials to serve these patients, given the paucity of data supporting licensed systemic therapies in this setting and the uncertainties involved in surgical therapy. Full-Text PDF