A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma
Introduction
Malignant pleural mesothelioma (MPM) is an aggressive form of malignancy with a dismal prognosis of less than 12 months from the time of diagnosis. The incidence of MPM is expected to peak in most industrial nations within the coming decade [1]. Currently, selected patients with resectable disease can be treated with a curative intent through macroscopic complete resection. This can be achieved by either extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication (P/D), both of which can be combined with a wide range of adjuvant therapies, such as chemoradiation, intrapleural chemotherapy and photodynamic therapy [2], [3], [4]. Technical aspects of these procedures have been described previously [5].
Despite encouraging results from large institutional reports and prospective registries involving multi-modality therapy, outcomes of EPP and extended P/D have been highly variable and the selection of the ‘preferred’ surgical procedure remains highly controversial within the thoracic community [6], [7]. Indeed, authors of a feasibility-testing randomized controlled trial have questioned the role of any form of radical surgery for patients with MPM [8], [9], [10]. The purpose of the present study was to review the current literature on perioperative and long-term outcomes of EPP and extended P/D, and to compare these two surgical procedures using the available evidence.
Historically, the definition of P/D has been inconsistent, varying from minimally-invasive partial pleural excisions with a palliative intent to radical resections involving the pericardium and hemidiaphragm with a curative goal. To clarify and unify the definition of P/D, the International Mesothelioma Interest Group (IMIG), in collaboration with the International Association for the Study of Lung Cancer (IASLC), recently published a Consensus Report that classified pleurectomy-related procedures into three well-defined categories according to surgical technique [11]:
- 1.
Extended P/D: parietal and visceral pleurectomy to remove all gross tumour with resection of the diaphragm and/or pericardium as required.
- 2.
P/D: parietal and visceral pleurectomy to remove all gross tumour without resection of the diaphragm or pericardium.
- 3.
Partial pleurectomy: partial removal of parietal and/or visceral pleura for diagnostic or palliative purposes but leaving gross tumour behind.
A systematic review of studies on extended P/D reported a perioperative mortality rate of 0–11% (inter-quartile 0–3.4%) and a morbidity rate of 20–43% [6]. Patients who underwent extended P/D were found to have a trend towards longer overall survival at the cost of higher perioperative morbidity and mortality when compared to patients who underwent P/D or partial P/D. This was likely a reflection of the more aggressive surgical approach by removing the diaphragm and/or pericardium to achieve macroscopic complete resection.
EPP involves en bloc resection of the visceral and parietal pleurae, lung, ipsilateral hemidiaphragm, and pericardium. As a result of removing the ipsilateral lung, local control of disease progression may be enhanced postoperatively by adjuvant high-dose radiotherapy, without the risk of radiation pneumonitis. A cross-sectional survey of thoracic surgeons with a special interest in MPM recently reported that 90% of respondents believed EPP to be capable of achieving macroscopic complete resection, as compared to 68% for extended P/D [11].
A systematic review of all studies on EPP reported an inter-quartile mortality rate of 3.7–7.6% and an inter-quartile median overall survival of 12–20 months [7]. A focused systematic review on trimodality therapy involving neoadjuvant or adjuvant chemotherapy, EPP and adjuvant radiotherapy reported a perioperative mortality rate of 0–12.5%, a morbidity rate of 50–83% and a median overall survival of 12.8–46.9 months [12]. Specifically, four prospective studies involving a standardized treatment regimen with neoadjuvant chemotherapy reported favourable survival outcomes of 16.8–25.5 months on intention-to-treat analysis [13], [14], [15], [16]. More recently, EPP has been described to be performed through the minimally invasive video-assisted thoracoscopic approach [17].
Section snippets
Literature search strategy
To compare the outcomes of patients who underwent EPP versus extended P/D, electronic searches were performed using Ovid Medline, Embase, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR), ACP Journal Club, and Database of Abstracts of Review of Effectiveness (DARE) from their dates of inception to September 2013. To achieve the maximum sensitivity of the search strategy and identify all studies, we combined the terms “mesothelioma” with
Quantity and quality of trials
A total of 155 references were identified through the six electronic database searches and additional sources. After exclusion of duplicate or irrelevant references, 37 potentially relevant articles were retrieved for more detailed evaluation. After applying the selection criteria, seven comparative studies remained for assessment [19], [20], [21], [22], [23], [24], [25]. Manual search of the reference lists did not identify any additional relevant studies. Of the seven studies included in the
Discussion
The present meta-analysis compared EPP with extended P/D using all the available evidence in the current literature. Prior to the reclassification of P/D by IMIG and IASLC, pleurectomy procedures varied significantly in surgical technique and therapeutic intent. Minimally invasive procedures consisting of little more than pleural biopsies were sometimes categorized with radical procedures that required extensive resection and reconstruction of the pericardium and diaphragm. By only including
Conflict of interest statement
None to declare.
Disclaimers
No potential conflicts of interest.
Funding
None
Acknowledgements
Sunil Gupta, Thomas Nienaber, David Chandrakumar for data editing; Nil funding sources declared.
References (29)
- et al.
A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma
J Thorac Cardiovasc Surg
(2009) - et al.
Surgical techniques for multimodality treatment of malignant pleural mesothelioma: extrapleural pneumonectomy and pleurectomy/decortication
Semin Thorac Cardiovasc Surg
(2009) - et al.
A systematic review of extrapleural pneumonectomy for malignant pleural mesothelioma
J Thorac Oncol
(2010) - et al.
The mesothelioma and radical surgery randomized controlled trial: The MARS feasibility study
J Thorac Oncol
(2009) - et al.
Benefit from surgical resection is questionable
Journal of Thoracic Oncology
(2007) - et al.
International Association for the Study of Lung Cancer International Staging C, the International Mesothelioma Interest G. Recommendations for uniform definitions of surgical techniques for malignant pleural mesothelioma: a consensus report of the international association for the study of lung cancer international staging committee and the international mesothelioma interest group
J Thoracic Oncol: Official Publication of the International Association for the Study of Lung Cancer
(2011) - et al.
Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): Feasibility and results
Lung Cancer
(2007) - et al.
Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma
Ann Oncol
(2007) - et al.
Pleurectomy/decortication is superior to extrapleural pneumonectomy in the multimodality management of patients with malignant pleural mesothelioma
J Thorac Oncol
(2012) - et al.
Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: a harmful procedure
Lung Cancer
(2012)
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
Lancet Oncol
The MARS feasibility trial: conclusions not supported by data
Lancet Oncol
The Mars trial: resolution of the surgical controversies in mesothelioma
J Thorac Oncol: Official Publication of the International Association for the Study of Lung Cancer
Malignant pleural mesothelioma: an epidemiological perspective
Ann Cardiothorac Surg
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