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

Our plain-English summary of 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, by E. Lim, L. Darlison, J. Edwards, et al (BMJ Open, 2020).

The study

• Authors: E. Lim, L. Darlison, J. Edwards, D. Elliott, D.A. Fennell, S. Popat, R.C. Rintoul, D. Waller, C. Ali, A. Bille, L. Fuller, A. Ionescu, M. Keni, A. Kirk, P. Koh, K. Lau, T. Mansy, N.A. Maskell, R. Milton, D. Muthukumar, T. Pope, A. Roy, R. Shah, J. Shamash, Z. Tasigiannopoulos, P. Taylor, S. Treece, K. Ashton, R. Harris, K. Joyce, B. Warnes, N. Mills, E.A. Stokes, C. Rogers, MARS 2 Trialists
• Journal: BMJ Open
• Published: 2020;10(9):e038892
• Cited by: 64 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left.

Methods And Analysis: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.

Ethics And Dissemination: Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal.

Trial Registration Numbers: ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

In plain English

This article was a published protocol describing the planned design of the MARS 2 trial. It reported no results on survival or other outcomes. MARS 2 was a randomised controlled trial in UK NHS hospitals. It tested whether surgery called (extended) pleurectomy decortication plus chemotherapy gives longer overall survival than chemotherapy alone. It enrolled adults with epithelioid, sarcomatoid or biphasic mesothelioma confined to one side of the chest and judged removable by surgery. After two cycles of platinum and pemetrexed chemotherapy, patients were assigned by chance to one of two groups. One group was assigned to surgery followed by up to four more cycles of chemotherapy. The other was assigned to chemotherapy alone, up to six cycles in total. The planned size was 328 participants, 164 per group. By 25 May 2020, 308 patients had been randomised, 66 of them from the pilot phase. The authors stated that it was not known whether this surgery with chemotherapy improves survival compared with chemotherapy alone. They noted that participants and the study team could not be blinded, and that patients might seek surgery outside their assigned group.

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: Protocol for a multicentre, open (non-blinded), parallel two-group, pragmatic randomised controlled trial in the UK. The primary outcome is overall survival.
• Who was studied: Adults aged 16 or older with tissue-confirmed epithelioid, sarcomatoid or biphasic mesothelioma, with disease confined to one side of the chest, judged surgically resectable and fit for surgery. They were treated at NHS secondary care centres in the UK, and recruitment started in May 2015.
• Exposure: No asbestos exposure was studied. The article mentions only as background that pleural mesothelioma is primarily due to asbestos exposure. The trial compared two assigned treatments. The first was two cycles of platinum and pemetrexed chemotherapy, then (extended) pleurectomy decortication, then up to four more cycles of the same chemotherapy. The second was up to six cycles of platinum and pemetrexed chemotherapy alone.
• Main results:
  • An earlier internal pilot phase showed that recruitment was feasible across 14 medical sites and 2 joint medical and surgical sites. This concerns recruitment, not treatment outcomes.
  • The planned total sample size was 328 participants (164 per group).
  • Study progress: 308 patients had been randomised as of 25 May 2020, including 66 patients from the pilot study. No outcome results were reported.
• The authors' conclusion: As a protocol, the article draws no conclusions about outcomes. The authors stated that it is unknown whether (extended) pleurectomy decortication with chemotherapy improves survival compared with chemotherapy alone.
• Limitations the authors state:
  • Neither participants nor the study team could be blinded to treatment, although the primary outcome (survival) is objective.
  • Patients may expect surgery to help, which can lead to crossovers. For example, patients allocated to no surgery may seek surgery elsewhere.
  • The quality-of-life follow-up questionnaires may be more at risk of bias than other measures.
  • Patient pathways varied between sites.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Systemic Therapy, Pemetrexed (Alimta), Median Overall Survival, Quality of Life, Pneumonectomy, Chemotherapy.

Related studies

• Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion — D.B. Fitzgerald, C. Sidhu, et al. (2022)
• Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study — N. Mills, N. Farrar, et al. (2024)
• Evaluating niraparib versus active symptom control in patients with previously treated mesothelioma (NERO): a study protocol for a multicentre, randomised, two-arm, open-label phase II trial in UK secondary care centres — D. Fennell, D. Griffiths, et al. (2023)
• Dual-functIon Semi-rigid thoraCoscOpy Versus semi-rigid thoracoscopy for the diagnosis of plEuRal diseases: protocol for a multicentre, open-label, randomised controlled trial in China (DISCOVER-I) — M. Deng, X. Liu, 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)
• Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters — M. Azzopardi, R. Thomas, et al. (2016)

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