Lim Eric, Opitz Isabelle, Woodard Gavitt, Bueno Raphael, de Perrot Marc, Flores Raja, Gill Ritu, Jablons David, Pass Harvey
Academic Division of Thoracic Surgery, Royal Brompton and Harefield NHS Trust, London, United Kingdom.
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
J Thorac Oncol. 2025 Mar;20(3):262-272. doi: 10.1016/j.jtho.2024.12.014. Epub 2025 Jan 8.
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.
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.
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.
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.
一项关于广泛性胸膜剥脱术加化疗与单纯化疗治疗胸膜间皮瘤（PM）的3期随机对照试验（MARS2）报告称，“与单纯化疗相比，广泛性胸膜剥脱术与2年生存率较低以及可切除性PM患者出现更严重不良事件相关”。这些结果引发了关于手术在PM治疗中未来作用的大量讨论，并且间皮瘤外科界对于该试验的解读尚未达成一致。本“观点”文章利用国际知名的PM专家对MARS2进行评估，这些专家要么认同该试验的解读，要么发现其实施过程中可能影响结果的问题。
一名协调人（HP）与团队负责人（GW、IO）合作，召集对该试验及其结论发表意见的人员。仅在完整试验发表后才撰写同意或不同意试验解读的观点。协调人收到双方观点后，将个人团队稿件合并并发送给每个团队，以便针对所察觉的事实错误进行编辑修改。
有见地的观点包括（但不限于）随机化的困难与优势、质量保证、组织学亚型的选择、随机化的时机、术前分期的使用、统计方法以及手术死亡原因。
未来针对PM是否进行手术的决策将继续由共识指南和医疗支付方的意愿来决定，而对MARS2的解读可能在调节未来手术的作用方面发挥重要作用。
