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

Our plain-English summary of 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, by T. Treasure, L. Lang-Lazdunski, D. Waller, et al (The Lancet. Oncology, 2011).

The study

• Authors: T. Treasure, L. Lang-Lazdunski, D. Waller, J.M. Bliss, C. Tan, J. Entwisle, M. Snee, M. O'Brien, G. Thomas, S. Senan, K. O'Byrne, L.S. Kilburn, J. Spicer, D. Landau, J. Edwards, G. Coombes, L. Darlison, J. Peto, MARS trialists
• Journal: The Lancet. Oncology
• Published: 2011;12(8):763-72
• Type of article: Randomized trial
• Cited by: 527 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.

Methods: MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524.

Findings: Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group.

Interpretation: In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients.

Funding: Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.

Copyright © 2011 Elsevier Ltd. All rights reserved.

In plain English

MARS, a randomised feasibility trial at 12 UK hospitals, compared extra-pleural pneumonectomy (EPP) plus radiotherapy with no EPP in patients with malignant pleural mesothelioma after platinum-based chemotherapy. Of 112 registered patients, 50 were randomised: 24 to EPP and 26 to no EPP. Of the 24 assigned to EPP, 16 completed the operation and three died perioperatively. Twelve-month survival was 52.2% (95% CI 30.5 to 70.0) for patients allocated to EPP and 73.1% (51.7 to 86.2) for those allocated to no EPP. The overall survival hazard ratio, EPP versus no EPP, was 1.90 (95% CI 0.92 to 3.93; p=0.082). After adjustment for sex, histological subtype, stage and age, it was 2.75 (1.21 to 6.26; p=0.016); values below 1 would have favoured EPP. Median survival from randomisation was 14.4 months (5.3 to 18.7) for the EPP group and an estimated 19.5 months (13.4 to not yet reached) for the no EPP group. Quality-of-life scores seemed lower in the EPP group, but differences were not statistically significant. The authors called the study small and concluded that these limited data suggest EPP within trimodal therapy offers no benefit and possibly harms patients.

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: multicentre randomised controlled feasibility trial with a prerandomisation registration phase; analyses by intention to treat; not masked
• Who was studied: Adults with pathologically confirmed malignant pleural mesothelioma considered fit for trimodal therapy, at 12 UK hospitals; 112 registered and 50 randomised (24 EPP, 26 no EPP) between Oct 1, 2005 and Nov 3, 2008
• Exposure: Not an asbestos exposure study. The treatment compared was EPP followed by radical (hemithorax) radiotherapy versus no EPP. All patients first received platinum-based chemotherapy.
• Main results:
  • Of the 112 registered patients, 62 did not go on to randomisation, mainly because of disease progression (33 patients)
  • In the group assigned to EPP, 16 of 24 patients completed EPP surgery
  • In the group assigned to EPP (intention to treat), there were three perioperative deaths in 24 patients (12.5%, 95% CI 2.7 to 32.4)
  • In the no EPP group, the one perioperative death was in a patient who had EPP outside the trial
  • Among the 16 who completed EPP, 11 had at least one postoperative complication
  • 12-month survival was 52.2% (95% CI 30.5 to 70.0) in those allocated to EPP and 73.1% (51.7 to 86.2) in those allocated to no EPP
  • Unadjusted hazard ratio for overall survival, EPP group versus no EPP group: 1.90 (95% CI 0.92 to 3.93; exact p=0.082); HRs less than 1.0 favoured EPP
  • After adjustment for prespecified prognostic factors (sex, histological subtype, stage, age), the hazard ratio was 2.75 (1.21 to 6.26; p=0.016)
  • Median survival from randomisation was 14.4 months (5.3 to 18.7) for patients allocated to EPP and an estimated 19.5 months (13.4 to time not yet reached) for patients randomised to no EPP
  • Quality-of-life questionnaires were completed by 12 patients in the EPP group and 19 in the no EPP group. Median scores seemed lower in the EPP group, lowest shortly after surgery, with no statistically significant differences between groups.
  • Serious adverse events: ten in the EPP group and two in the no EPP group
• The authors' conclusion: The authors concluded that these limited data suggest EPP within trimodal therapy offers no benefit and possibly harms patients. Given the high morbidity of EPP, they judged a larger study not feasible.
• Limitations the authors state:
  • The authors stated the study was small and its conclusions must be guarded
  • The authors stated that a much larger study with longer follow-up would be needed for reliable evidence on mortality patterns and long-term survival
  • The authors noted protocol compliance problems: some patients allocated to no EPP pursued radical surgery outside the trial
  • Patients and investigators knew which treatment each patient was allocated

Topics

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

Medical terms in this study, explained in our Lexicon: Pneumonectomy, Pleural Mesothelioma, Mesothelioma, Quality of Life, Chemotherapy, Hemithorax, Disease Progression, Hazard Ratio.

Related studies

• Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma — Y. Matsuo, K. Shibuya, et al. (2017)
• Surgery for mesothelioma: MARS landing and future missions — T. Treasure (2010)
• National Cancer Database Report on Pneumonectomy Versus Lung-Sparing Surgery for Malignant Pleural Mesothelioma — V. Verma, C.A. Ahern, et al. (2017)
• How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma? — A.J. Sharkey, K.J. O'Byrne, et al. (2016)
• A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma — B.C. Cho, R. Feld, et al. (2014)
• Extra-pleural pneumonectomy in the era of image-guided intensity-modulated radiotherapy — M. Trovo, D. Franceschini, et al. (2019)

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