The Role of Surgery in Pleural Mesothelioma: A Journey through the Evidence, MARS 2 and Beyond

Our plain-English summary of The Role of Surgery in Pleural Mesothelioma: A Journey through the Evidence, MARS 2 and Beyond, by A. Aujayeb, P. Astoul, F. Londero, et al (Pulmonary Therapy, 2025).

The study

• Authors: A. Aujayeb, P. Astoul, F. Londero, A. Zuin
• Journal: Pulmonary Therapy
• Published: 2025;11(2):117-127
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural mesothelioma (PM) is a rare incurable disease, predominantly linked to asbestos exposure. Not only is diagnosis difficult, but treatment choices are often limited to systemic anti-cancer treatment with chemotherapy or immunotherapy. Surgery has been employed for decades, but its application has been fiercely debated despite some randomized controlled trials such as the recent Mesothelioma and Radical Surgery 2 (MARS 2) study. We provide a commentary on this controversial topic.

© 2025. The Author(s).

In plain English

This article was a commentary and narrative review, with no new study of patients. The authors reviewed published evidence on surgery for pleural mesothelioma, a cancer they said usually affects people with occupational asbestos exposure. They focused on the MARS 2 randomized trial, reported as enrolling 355 patients. After two cycles of chemotherapy, it compared surgery (pleurectomy/decortication or its extended form) plus further chemotherapy with chemotherapy alone. Median survival was 19.3 months with surgery and 24.8 months with chemotherapy alone. The surgery group had significantly more serious adverse events, and higher costs. The review also described the earlier MARS trial. It assigned 24 patients to extra-pleural pneumonectomy and 26 to no extra-pleural pneumonectomy. The operation showed no overall survival advantage, an increased risk of death and poorer quality of life. The authors listed criticisms of MARS 2: it included non-epithelioid tumours, and staging relied mainly on CT scans. They also said its death rate of 9% at 3 months after surgery far exceeded rates typically reported. The authors concluded that surgery should not be ruled out and that MARS 2 should prompt more refined patient selection.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Commentary and narrative review combined with the authors' expert opinion; no new study with human participants
• Who was studied: No patients were studied directly. The authors reviewed previously published studies and guidelines on surgery for pleural mesothelioma, with a critical appraisal of the MARS 2 trial.
• Exposure: No exposure was studied. The article is about surgical treatment: extra-pleural pneumonectomy, and pleurectomy/decortication in standard or extended form. It notes that the typical patient usually has a history of occupational asbestos exposure.
• Main results:
  • As reported by the review, MARS 2 was a phase III trial that enrolled 355 patients.
  • As described by the review, MARS 2 randomized patients after two cycles of chemotherapy. The surgery group received pleurectomy/decortication (PD) or extended pleurectomy/decortication (E/PD), followed by two to four further cycles of chemotherapy. The other group received chemotherapy alone.
  • As reported by the review, in the MARS 2 trial median survival was shorter in the surgery group (19.3 months) than in the chemotherapy-alone group (24.8 months).
  • In the review's figure from MARS 2, the probability of being alive at 24 months was 0.41 (95% CI 0.34 to 0.49) in the surgery group and 0.52 (0.44 to 0.59) in the no-surgery group.
  • As reported by the review, the MARS 2 surgery group had significantly more serious adverse events, including a threefold increase in complications such as cardiac and respiratory disorders.
  • In the authors' view, the MARS 2 perioperative death rate of 9% at 3 months far exceeded rates typically reported in other studies.
  • The review noted criticism that MARS 2 included patients with both epithelioid and non-epithelioid subtypes of mesothelioma.
  • The review noted criticism that MARS 2 staging relied mainly on CT scans, without mandatory PET-CT or invasive mediastinal staging.
  • As reported by the review, MARS 2 found that extended pleurectomy/decortication was associated with higher costs and fewer quality-adjusted life years than chemotherapy alone.
  • As described in the review, the earlier MARS trial assigned 24 patients to extra-pleural pneumonectomy and 26 to no extra-pleural pneumonectomy. With extra-pleural pneumonectomy, it found no overall survival advantage, an increased risk of death and poorer quality of life.
• The authors' conclusion: The authors concluded that the role of surgery should not be definitively ruled out. They viewed MARS 2 as a reason to refine surgical indications and methods, not to abandon surgery. They called for further trials with more refined criteria, such as operating only on patients with epithelioid, limited-stage disease and perhaps using diaphragm-sparing operations.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Chemotherapy, Immunotherapy, Mesothelioma.

Related studies

• SMART: logical radiotherapy and surgery beyond MARS — H.I. Pass (2021)
• Beyond Asbestos: Malignant Pleural Mesothelioma Revealing Lynch Syndrome Through Mismatch Repair Deficiency — S. Vivanco, S. Vega, et al. (2026)
• Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study — T. Treasure, L. Lang-Lazdunski, et al. (2011)
• Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma — E. Lim, L. Darlison, et al. (2020)
• Surgery in mesothelioma--where do we go after MARS? — B.I. Hiddinga, J.P. van Meerbeeck (2013)
• Patient experiences of participation in a radical thoracic surgical trial: findings from the Mesothelioma and Radical Surgery Trial 2 (MARS 2) — C. Warnock, K. Lord, et al. (2019)

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