Malignant pleural mesothelioma is an aggressive cancer of the pleura that is associated with exposure to fibrous minerals in the environment, such as asbestos or erionite. Because asbestos is ubiquitous in building material, the worldwide incidence of the disease continues to rise; rates in Europe are expected to increase by 5—10% per year for the next 25 years.1 Left untreated, the prognosis of malignant pleural mesothelioma is poor, with median overall survival of 7 months.1 Diagnosis of early disease is rare, because symptoms, such as dyspnoea or chest wall pain, often do not occur until later stages. Suspicion must be high to make the diagnosis, because the disease often presents as a pleural effusion or pleural thickening on imaging, or both, making it difficult to differentiate from other diseases.2

Once malignant pleural mesothelioma is suspected, a tissue sample is obtained in the operating room via pleuroscopy or video-assisted thoracoscopy, with incisions placed in a potential future thoracotomy site.1 Pleural fluid cytology and needle biopsy are often insufficient, because adequate specimens are needed to establish whether invasion is present and distinguish malignant disease from fibrous exudate or proliferating mesothelial cells. Additionally, enough tissue should be obtained to identify the histological subtype: epithelial, sarcomatoid, or mixed (biphasic).2, 3

Prognostic factors that portend increased survival include epithelial histology, female sex, and earlier stage. In a retrospective study of 945 patients,4 longer survival was associated with these characteristics, as well as no history of smoking or asbestos exposure, and left-sided tumours. The longest survival is recorded in women younger than 50 years and those with epithelial disease, for whom median survival exceeds 30 months.5 The difference between the sexes is a consistent finding and suggests that circulating oestrogen might affect tumour biology.3, 5, 6

While trials assess the roles of neoadjuvant or adjuvant chemotherapy, radiation therapy, intracavitary chemotherapy, photodynamic therapy, and other systemic options, the standard of care is resection and adjuvant therapy with radiation or chemotherapy, or both.6 Most studies have suggested that patients with favourable disease characteristics benefit from surgery with curative intent in the context of multimodality therapy.1, 2, 7

The two options for surgical resection are extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). With EPP, the pleural envelope is resected along with its contents, including the lung, diaphragm, and pericardium. P/D is a similar radical resection, but preserves the lung. Until 10 years ago, many surgeons preferred EPP for macroscopic complete resection, even in early-stage disease, as long as the patient had adequate cardiopulmonary function. Critics of EPP suggested that it was associated with high risk and did not offer a clear survival benefit. The Mesothelioma and Radical Surgery trial8 was designed to assess the role of EPP in malignant pleural mesothelioma, but its design was not feasible due to the high morbidity associated with EPP, and subsequent exploratory analyses were done with sample sizes that did not have adequate power to draw meaningful conclusions.

Many surgeons have recognised that macroscopic complete resection can be accomplished with P/D and with less morbidity than with EPP, particularly for early-stage disease. A multi-institutional retrospective study of 663 patients9 showed that, when undertaken as part of a multimodality treatment plan with curative intent, cumulative survival for early-stage disease was higher for P/D than for EPP. For later-stage disease, survival was higher with EPP. A subsequent study3 assessed 42 patients with International Mesothelioma Interest Group stage III disease undergoing P/D and adjuvant chemoradiation. Macroscopic complete resection was possible in 26 (62%), and median survival after this procedure was 35 months compared with 13 months in the 16 patients with incomplete resections.3 These data suggest that, as long as macroscopic resection of gross disease can be achieved, which operation to undertake depends on the individual patient’s tumour and functional status.7 This conclusion is reflected in the most recent clinical guidelines that were formulated by the 2012 International Mesothelioma Interest Group Congress (panel).10 Moreover, as techniques and perioperative management have improved, the mortality rates associated with these procedures—which were once prohibitively high—are now only 2·2—7% for EPP and 1—5% for P/D.2, 7, 9

Panel

Surgical recommendations discussed at the 2012 International Mesothelioma Interest Group Congress10

• Surgical macroscopic complete resection and control of micrometastatic disease have an important role in the multimodality therapy of malignant pleural mesothelioma, as for other solid malignancies.
• Surgical cytoreduction is indicated when macroscopic complete resection is deemed achievable.
• The type of surgery (extrapleural pneumonectomy or pleurectomy/decortication) depends on clinical factors and on individual surgical judgment and expertise.
• All patients with the diagnosis of malignant pleural mesothelioma should be initially assessed in a multidisciplinary setting, by medical oncology, radiation oncology, and surgical teams.
• Clinical staging (lymph-node sampling, PET, and MRI) should be done before treatment.
• The histological subtype should be identified by tissue biopsy before initiation of treatment.

Source: Lancet