Cytoreductive surgery in diffuse pleural mesothelioma. What have we learnt from MARS2, EORTC-L1205 and other recent studies?

Cytoreductive surgery remains controversial in pleural mesothelioma. The MARS2 trial suggested that extended pleurectomy decortication following neoadjuvant chemotherapy was associated with no survival benefit, more serious adverse events and poorer quality of life than systemic chemotherapy alone in patients with resectable pleural mesothelioma. However, patient selection, chemotherapy scheme, high surgical mortality (9 %) and poor outcomes in the surgical cohort have been raised by mesothelioma experts as potential issues in MARS2. The EORTC-L1205trial reported high morbidity, but low surgical mortality (1.7 %) and more favourable outcomes, suggesting that well-selected patients could benefit from extended pleurectomy decortication and systemic chemotherapy. Other recently-published studies show that cytoreductive surgery remains a valuable option in well-selected patients offering median survivals of 34-38 months, when the best systemic options combining chemotherapy agents, anti-angiogenics or immune checkpoint inhibitors offer median survivals of 18-24 months. Careful patient selection is essential to avoid futile or detrimental surgery and there is evidence that preservation of the diaphragm is associated with lower morbidity and mortality, better long-term outcomes.