Surgery in the treatment of malignant pleural mesothelioma: recruitment into trials should be the default position

Our plain-English summary of Surgery in the treatment of malignant pleural mesothelioma: recruitment into trials should be the default position, by A. Datta, R. Smith, F. Fiorentino, et al (Thorax, 2014).

The study

• Authors: A. Datta, R. Smith, F. Fiorentino, T. Treasure
• Journal: Thorax
• Published: 2014;69(2):194-7
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Europe is at the peak of an epidemic of malignant pleural mesothelioma and the burden of disease is likely to continue rising in the large areas of the world where asbestos remains unregulated. Patients with mesothelioma present with thoracic symptoms and radiological changes so respiratory physicians take a leading role in diagnosis and management. Belief that the modest survival times reported after radical surgery, whether alone or as part of multimodal therapy, are longer than they it would have been without surgery relies on data from highly selected, uncontrolled, retrospectively analysed case series. The only randomised study, the Mesothelioma and Radical Surgery (MARS) trial showed no benefit. A simple modelling study of registry patients, described here, shows that an impression of longer survival is eroded when patients who were never candidates for operation on grounds of histology, performance status and age are sequentially excluded from the model.

Conclusion: Whenever the question arises `Might an operation help me?' there are two responses that can and should be given. The first is that there is doubt about whether there is any survival or symptomatic benefit from surgery but we know that there is harm. The second is that there are on-going studies, including two randomised trials, which patients should be informed about. The authors suggest that the default position for clinicians should be to encourage recruitment into these trials.

In plain English

This was an opinion article about surgery for malignant pleural mesothelioma. The authors argued that belief in a survival benefit from radical surgery relies on highly selected, uncontrolled case series. To show how patient selection can create this impression, they used the York Teaching Hospital Cancer Registry. There, 10 of 123 patients diagnosed between November 2002 and November 2011 had extrapleural pneumonectomy (EPP). Median survival was 12.6 months for the 10 EPP patients and 6.1 months for the 113 who did not have EPP. The authors then removed, step by step, non-operated patients with sarcomatoid histology, poor performance status (2, 3 or 4) or age over 76.2 years. That left 49 patients, with a median survival of 11.4 months. The authors said that if other factors such as tumour bulk and lymph node involvement had also been balanced, the gap would likely have narrowed further. They discussed other studies, including the MARS randomised trial, which they described as showing no benefit. The authors concluded that, given the lack of good quality evidence, recruitment into one of two trials should be the default position.

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: Opinion article that includes a simple illustrative survival comparison using cancer registry data (Kaplan Meier estimates with stepwise exclusion of non-comparable patients)
• Who was studied: 123 patients diagnosed with mesothelioma between November 2002 and November 2011 in the Cancer Registry of York Teaching Hospital, UK. 10 of them had EPP and 113 did not.
• Exposure: The comparison was treatment with extrapleural pneumonectomy (EPP) versus no EPP. Asbestos exposure was not studied.
• Main results:
  • The 10 patients who had EPP had a median survival of 12.6 months (IQR 5.6 to 17.7 months).
  • All 113 patients who did not have EPP had a median survival of 6.1 months (IQR 2.2 to 12.8 months).
  • After 11 non-operated patients with sarcomatoid histology were excluded, 102 remained, with a median survival of 6.15 months (IQR 2.2 to 13.3 months).
  • After a further 29 non-operated patients with performance status 2, 3 or 4 were excluded, 73 remained, with a median survival of 9.6 months (IQR 4.8 to 18.1 months). Patients with missing performance status were kept in.
  • After a further 24 non-operated patients older than 76.2 years (the age of the oldest EPP patient) were excluded, 49 remained, with a median survival of 11.4 months (IQR 5.9 to 19.4 months).
  • The authors stated that well over half of the non-operated patients in York were never candidates for surgery on the criteria recorded in the database.
  • The authors reported that the impression of longer survival after surgery was eroded as patients who were never candidates for operation were excluded.
• The authors' conclusion: The authors concluded that, given the lack of good quality evidence, recruitment into one or other of two ongoing trials should be the default position for patients being considered for surgery.
• Limitations the authors state:
  • Other factors used in surgical decisions, such as tumour bulk, invasiveness and lymph node involvement, were not balanced between the groups. The authors said the survival gap would likely have narrowed further if they had been.

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: Pleural Mesothelioma, Mesothelioma, Multimodal Therapy, Histology, Performance Status.

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• Should we continue to offer extrapleural pneumonectomy to selected mesothelioma patients? A single center experience comparing surgical and non-surgical management — M. Baud, A. Bobbio, et al. (2014)
• MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial — C. Matthews, C. Freeman, et al. (2019)
• Summary of prognostic factors and patient selection for extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma — C. Cao, T.D. Yan, et al. (2011)
• Surgery as part of radical treatment for malignant pleural mesothelioma — D.A. Waller, S. Tenconi (2017)
• How successful is lung-preserving radical surgery in the mesothelioma and radical surgery-trial environment? A case-controlled analysis — Y. Shahin, J. Wellham, et al. (2011)

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