The role of surgery in malignant mesothelioma is one of the field’s most controversial issues, with the MARS2 trial bringing that divide into sharper focus in recent years. That uncertainty was on full display during a spirited back-and-forth debate at the 2026 Targeted Therapies of Lung Cancer (TTLC) meeting, on Friday, February 20, in Huntington Beach, California.
Leah Backhus, MD, MPH, Professor of Cardiothoracic Surgery at Stanford Medicine, faced medical oncologist Gregory Kalemkerian, MD, Clinical Professor of Medical Oncology at the University of Michigan, to debate the role of surgery in the treatment of malignant pleural mesothelioma (MPM).
Arguing in favor of surgery, Dr. Backhus began by acknowledging the findings of the MARS2 trial, in which extended pleurectomy/decortication (P/D) was associated with worse 2-year survival and more serious adverse events in patients with resectable MPM compared with chemotherapy alone.
However, she emphasized that surgery should not be viewed as a stand-alone option, but rather as one component of a multimodality treatment strategy.
“No one—myself included—is standing up here trying to say we should do surgery and that this is the end-all, be-all for patients with mesothelioma,” she said. “Clearly, you have to have systemic therapy at some point. It is incredibly important that patients receive multimodality therapy as we approach their care.”
Within that framework, Dr. Backhus argued that surgical outcomes depend heavily on the performance of the appropriate procedure, technical expertise, and appropriate patient selection, particularly the ability to achieve adequate resection.
“Surgery is better than no surgery or best supportive care, but within the context of surgery, a complete resection—that is, attempting to achieve an R1 resection, because we can never obtain an R0—is incredibly important,” she said. “If you don’t do that, the outcomes associated with surgery are diminished significantly.”
Dr. Backhus pointed in particular to the 16% rate of incomplete (R2) resections in the MARS2 surgical arm, indicating macroscopic residual disease—an outcome associated with poorer surgical results.
Taken together, she argued, the MARS2 trial primarily clarified which patients are not appropriate surgical candidates rather than demonstrating that surgery itself lacks benefit. She concluded by pointing to National Comprehensive Cancer Network guidelines, which continue to include surgery within multimodality treatment discussions for select patients.
“We’re still in the discussion,” she said. “We still should be a part of the dialogue with our patients as we discuss multimodality therapy for them.”
In response, Dr. Kalemkerian centered his position on randomized trial evidence, which he said consistently demonstrates worse outcomes with surgical resection in MPM. The original MARS trial (MARS1), for example, evaluated extrapleural pneumonectomy (EPP) compared with no EPP and found worse survival and quality of life among patients who underwent surgery.
Dr. Kalemkerian then noted that even within surgical approaches, less extensive procedures have appeared to perform better than more radical ones—a pattern he said that further highlights the risks associated with aggressive surgical intervention.
Turning to the more recent MARS2 trial, he emphasized that chemotherapy alone outperformed surgical management.
“What MARS2 showed was that not doing a P/D and just having chemotherapy was actually superior to P/D with regard to survival, mortality, and quality of life,” he said.
He argued that when randomized evidence demonstrates harm, the intervention in question—in this case, surgery—should not be pursued in routine clinical practice. Dr. Kalemkerian also pointed to recommendations from major oncology organizations, which he said reflect similar caution regarding surgical management.
“ASCO (American Society of Clinical Oncology) states that surgical cytoreduction should not be routinely offered, and if surgery is pursued, it should preferably be performed within clinical trials,” he said, adding that the recommendation highlights the investigational nature of the procedure.
He noted that the European Society for Medical Oncology (ESMO) similarly cites negative randomized data from the MARS1 trial and emphasizes the potential impact of selection bias in registry studies reporting favorable surgical outcomes.
In concluding his argument, Dr. Kalemkerian said the available evidence does not support surgical management for MPM.
“Surgery should not be performed for MPM,” he said. “Randomized trials have shown worse survival and poorer quality of life; surgical procedures carry substantial morbidity and mortality, and the single-arm data supporting surgery are heavily confounded by selection bias.”
