Elsevier

Lung Cancer

Volume 83, Issue 2, February 2014, Pages 240-245
Lung Cancer

A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma

https://doi.org/10.1016/j.lungcan.2013.11.026Get rights and content

Abstract

Background

Malignant pleural mesothelioma (MPM) is an aggressive disease of the pleural lining with a dismal prognosis. Surgical treatments of MPM with a curative intent include extrapleural pneumonectomy and extended pleurectomy/decortication (P/D). This meta-analysis aimed to compare the perioperative and long-term outcomes of EPP and extended P/D for selected surgical candidates.

Methods

A systematic review of the literature was performed on six electronic databases to identify all relevant data on comparative outcomes of extended P/D and EPP in a multimodality setting. Endpoints included perioperative mortality and morbidity, as well as long-term overall survival.

Results

Seven relevant studies with comparative data on EPP (n = 632) versus extended P/D (n = 513) were identified from the current literature. Comparison of these two groups demonstrated significantly lower perioperative mortality (2.9% vs 6.8%, p = 0.02) and morbidity (27.9% vs 62.0%, p < 0.0001) for patients who underwent extended P/D compared to EPP. Median overall survival ranged between 13–29 months for extended P/D and 12–22 months for EPP, with a trend favouring extended P/D.

Conclusions

Although it must be emphasized that patient selection and treatment strategies differ between EPP and extended P/D, a number of comparative studies have recently been conducted to compare these two surgical techniques for patients with resectable MPM. The present study indicated that selected patients who underwent extended P/D had lower perioperative morbidity and mortality with similar, if not superior, long-term survival compared to EPP, in the context of multi-modality therapy. This may represent an important paradigm shift in the surgical management of MPM.

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.

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