Surgical trials in mesothelioma—past, present and future

Surgery in malignant pleural mesothelioma (MPM) has been undertaken for many years, but radical surgery remains a controversial issue. Numerous non-randomised studies have been performed but these are predominately uncontrolled case series or cohort studies which are limited by selection bias. High-level evidence has been gained from two published randomised trials performed in the United Kingdom and two further randomised trials are currently recruiting. It is widely accepted that clear microscopic margins, the goal of radical resection in cancer surgery, cannot be achieved in mesothelioma and therefore the aim is to achieve complete macroscopic resection (CMR). The least invasive surgical option is a video assisted thoracoscopic surgery partial pleurectomy (VATS-PP), investigated in the MesoVATS trial. MesoVATS showed no statistical difference in overall survival but a worse survival than the non-surgery group for those with high prognostic risk. There was slight improvement in quality life for low risk patients in the VAT-PP group. The MesoTRAP trial is currently randomizing patients with a trapped lung requiring an indwelling pleural catheter (IPC) between VATS-PP or IPC alone. MARS was a feasibility randomised trial of extrapleural pneumonectomy (EPP) and its results have been debated extensively. Recruitment was slow and protocol compliance poor. Although underpowered for clinical outcomes, EPP may be potentially harmful to patients and this procedure has fallen from favour internationally. The MARS-2 trial is currently recruiting, analyzing the role of extended pleurectomy/decortication (EP/D) versus no surgery. Patients are randomised if there is no CT evidence of disease progression following 2 cycles of standard of care chemotherapy. This article will discuss the past and current surgical trials in MPM, the limitations of these and what evidence we can draw upon for current clinical practice. The current and future trials along with international clinical guidelines will be discussed.