Review Article
Surgery for malignant pleural mesothelioma

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Introduction

Malignant pleural mesothelioma (MPM) remains a challenging disease from the surgical perspective. Its diffuse nature with involvement of the lung, pericardium, and diaphragm; the inability to reliably obtain negative margins; the significant morbidity and mortality associated with radical resection; and most importantly, the high recurrence rate after surgery, all contribute to the nihilistic attitude with which most clinicians view this disease. Despite major improvements in operative mortality over the last 2 decades, which is now between 2% and 8% at most centers, surgery alone is associated with high rates of local failure. For this reason, adjuvant and neoadjuvant modalities have been integrated into the surgical management of MPM. In most centers today, aggressive therapeutic approaches involve a trimodality regimen including extrapleural pneumonectomy (EPP), radiation therapy, and chemotherapy. The low incidence of MPM (2500-3000 cases per year in the United States) has contributed to the lack of reliable clinical data regarding optimal therapy for this disease. Most surgical series have been single-center retrospective studies that have spanned many years or prospective phase I and II trials that have involved small numbers of patients. To date, there has been no randomized study that has included surgery in the therapeutic regimen. Evidence for the efficacy of surgery has been largely based on comparison of highly selected patients who have undergone resection to unselected historical controls. Comparisons between retrospective studies in MPM are confounded by numerous factors including:

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    Differences in survival calculations—some studies measure survival from date of diagnosis, others by date of treatment.

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    Lack of uniform staging—in addition to multiple staging systems, there is no adequate clinical (preoperative) system available. Furthermore, many studies do not report stage.

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    Variable reporting of histologic subtypes.

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    Differences regarding indications for a given therapeutic intervention.

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    Variability in treatments applied to patient subgroups within larger series.

Understanding these major limitations, however, it is appropriate to examine the available data regarding therapeutic intervention for this disease. The following paragraphs will summarize what is currently known about the clinical treatment of this disease, with an emphasis on surgical management.

Section snippets

Natural history

The natural history of mesothelioma is for tumor to progress locally causing dyspnea, by either lung entrapment or compression from effusion leading to atelectasis and shunting, and worsening pain from chest wall invasion. Death usually occurs from 6 to 12 months from initial diagnosis. Metastases occur in 50% to 75% of cases; however, most are clinically occult and are not usually the cause of death in untreated patients. It should be noted however that MPM is usually diagnosed when it is in

Chemotherapy

Mesothelioma has generally been considered to be resistant to chemotherapy. Numerous single-agent phase I and II studies have shown response rates of 3% to 12% for non–platinum-based agents; 12% for anthracycline-based regimens; and 10% to 20% for platinum-based compounds. Platinum-based combination therapy has generally yielded better results than single-agent regimens, and 2 recent large randomized trials have shown improved efficacy of antifolate agents in combination with cisplatin. The

Surgery

There is considerable controversy regarding the optimal surgical strategy for mesothelioma. There are 2 main surgical options available—extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). The techniques of EPP have been well described, and the operation is usually performed in a uniform manner with en bloc resection of the affected lung and pleura, pericardium, and hemidiaphragm. Pleurectomy/Decortication, depending on the surgeon, may refer to anything from a procedure that

Staging

Accurate assessment of clinical stage is notoriously difficult for MPM. The most useful radiographic modality is computed tomography (CT) of the chest and upper abdomen. Computed tomography provides information regarding tumor volume and extent, pleural effusion, regional lymphadenopathy, and occasionally metastatic disease. Chest wall invasion may occasionally be obvious, but subtle invasion of the endothoracic fascia or intercostal muscles may not be identified. Similarly, CT is not usually

Extrapleural pneumonectomy

Extrapleural pneumonectomy involves the complete en bloc resection of the parietal pleura, visceral pleura, lung, ipsilateral pericardium, and diaphragm (Fig. 1). The latter structures are usually reconstructed with polytetrafluoroethylene (PTFE). Extrapleural pneumonectomy generally provides a more complete cytoreduction, even compared to radical P/D, and has the advantage that high-dose hemithoracic radiation may be administered to the postpneumonectomy space. Hemithoracic radiation after P/D

Pleurectomy/Decortication

Pleurectomy/decortication ideally involves the complete removal of the parietal and visceral pleura as well as all macroscopic tumor (Fig. 2). As previously mentioned, there is wide variance in the degree to which surgeons perform P/D in terms of the completeness of macroscopic tumor removal. Radical P/D begins with complete extrapleural mobilization of the lung to the level of the hilar structures. If the pleura/tumor is inseparable from the pericardium or diaphragm (as it often is), then

Extrapleural pneumonectomy versus P/D

There is considerable controversy over the selection of which operation is the most appropriate. Some surgeons perform only EPP, others only P/D, and many tailor selection of operation to the patient and the degree of tumor load. As previously mentioned, in addition to any putative oncologic pros and cons of either operation, selection must also take into account the availability of adjuvant therapies as well as patient- and tumor-related factors. Clearly, an elderly patient (older than 75

Summary

Controversy remains regarding the optimal therapy for MPM. In fit patients with epithelioid tumors and negative nodes, cytoreductive surgery combined with appropriate adjuvant or neoadjuvant therapy may improve survival compared to best supportive care or chemotherapy alone, although this is unproven. An ongoing randomized trial is currently underway in the United Kingdom that will compare trimodality therapy including EPP to trimodality therapy without EPP [33]. Complete removal of all

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References (33)

  • MoskalT.L. et al.

    Operation and photodynamic therapy for pleural mesothelioma: 6-year follow-up

    Ann Thorac Surg

    (1998)
  • FriedbergJ.S. et al.

    A phase I study of Foscan-mediated photodynamic therapy and surgery in patients with mesothelioma

    Ann Thorac Surg

    (2003)
  • FloresR.M. et al.

    Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center

    J Thorac Oncol

    (2007)
  • RuffieP. et al.

    Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients

    J Clin Oncol

    (1989)
  • MerrittN. et al.

    Survival after conservative (palliative) management of pleural malignant mesothelioma

    J Surg Oncol

    (2001)
  • VogelzangN.J. et al.

    Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma

    J Clin Oncol

    (2003)

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