• This manual is not a substitute for consultation with an appropriate specialist.
• The contents of this manual have been developed through consensus of a Provincial Tumour Group. Please note the various update dates for each section as some of the content of the manual may not be up to date.

Chair 

Dr. Stephen Lam, Respiratory Medicine, Vancouver General Hospital

Members​

Mesotheliomas are uncommon tumours arising from the mesothelial surface (pleura, peritoneum, and rarely from sites such as the pericardium and tunica vaginalis testis). Diffuse mesotheliomas are invariably malignant. At the time of presentation, pleural mesothelioma usually is often confined to the thorax, however, disease typically contaminates the entire pleural cavity and pleural effusion is common. Later, there is extension to the chest wall, mediastinum and encasement of the lung with a thick rind of tumour. Regional lymph nodes may become involved. Extension through the diaphragm may cause peritoneal involvement and ascites. Hematogenous metastases are uncommon but may be seen particularly in patients surviving longer than average.

Patients may present with chest pain, dyspnea and cough. The referring clinical problem may be pleural effusion of unknown etiology. Advancing disease causes respiratory insufficiency, chest wall pain, cardiovascular complications from invasion of the heart and general constitutional deterioration.

(Revised May 2001)

Mesotheliomas are uncommon, but not rare; 60-90 cases are diagnosed per year in British Columbia.

Incidence

Annual incidence is estimated at 1-2 per 100,000 per year. Mesothelioma is approximately five times more common in men than women. 

Age

Incidence rises with age and is approximately 10-fold higher in men between the ages of 60 and 64 years than among those between 30 and 34 years. The median age of diagnosis is 60 years, and is determined by the age at the time of asbestos exposure rather than other factors.

Survival 

Adverse prognostic factors include: poor performance status, advanced stage, leukocytosis, male gender, sarcomatoid histology, and presence of chest pain. Median survival is 10-12 months, and two-year survival rate is 15-20%. The presence of three or more adverse prognostic factors reduces median survival to < 6 months. Median survival of stage I disease has been reported to be 16 months. A minority of cases can be indolent and associated with survival for several years, independent of treatment. However, reports of long-term disease-free survivors are anecdotal.

References: 

1. Canadian Cancer Society's Steering Committee on Cancer Statistics. Canadian Cancer Statistics 2013. Toronto, ON, 2013

2. Chailleux E, Dabouis G, Pioche D, et al: Prognostic factors in diffuse malignant pleural mesothelioma: a study of 167 patients. Chest 1988;93:159-162.  

3. Curran D, Sahmoud T, Therasse P, et al. Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. J Clin Oncol 1998;16:145-52

4. Ruffie P, Feld R, Minkin S, et al: Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients. J Clin Oncol 1989;7:1157-1168.  

The association between asbestos and mesothelioma is well established, and a definite history of exposure is present in 70-75% of cases. Occupational exposure to asbestos in mines, mills, industry, mining, plumbing, insulating, construction, and among longshoremen and shipyard workers should be documented for medicolegal and workers' compensation purposes. Clinicians considering the diagnosis of mesothelioma should take a detailed exposure history, emphasizing the period between 20-50 years before diagnosis and including possible household contact exposure. Brief exposures may be long forgotten.

Since the early 1970's, legislation has decreased contamination of the environment by asbestos. The presence of asbestos fibres in the lungs of members of the general population suggests that exposure may occur unknowingly.

Reference: 

1. Committee on Asbestos: Selected Health Effects. Asbestos: Selected Cancers. Washington, DC: The National Academies Press, 2006.

2. McDonald AD, McDonald JC. Epidemiology of malignant mesothelioma. In: Antman K, Aisner J, eds. Asbestos-related malignancy. Orlando: Grune & Stratton, 1987:31-55.

Malignant mesothelioma is rarely curable, and screening of workers exposed to asbestos for mesothelioma is not recommended, as it is not known to improve survival. However, early detection may have a bearing on compensation.​

Smoking greatly increases the risk of lung cancer (but not mesothelioma) in asbestos workers, and smoking cessation efforts are warranted in this high-risk group. Screening for lung cancer may be warranted.

1 Clinicopathologic Considerations 

The pathology of mesothelioma is classically biphasic with both epithelioid and sarcomatoid areas present. Monophasic tumours exist and pure epithelioid lesions can be difficult to differentiate from peripheral anaplastic lung carcinomas or metastatic carcinomas. Special stains reported to be most useful include calretinin, CK5/6, WT-1, and D2-40, while TTF-1, CEA, BerEP4, CD15 and B72.3 may help with the differential diagnosis. Histologic appearance appears to be of prognostic value, with most clinical studies showing that epithelioid mesotheliomas have a better prognosis than fibrous or sarcomatoid mesotheliomas.

2 Diagnostic Procedures

As many patients with mesothelioma present with a pleural effusion, they usually undergo thoracentesis and pleural fluid pathology is positive in about one third of cases. It is difficult to differentiate metastatic adenocarcinoma from mesothelioma with cytology alone. If the pleural space is totally or partially free, thoracoscopy is a very good approach to diagnosis because it commits the patient to a very limited surgical procedure, allows direct examination of clinically abnormal tissues and provides the pathologist with a good specimen obtained from an involved area. If the pleural space is obliterated by adhesions or tumour, diagnostic limited thoracotomy may be required.

References: 

1. Bolen JW, Thorning D, Mesotheliomas: A light and electron microscopic study concerning the histogenic relationships between the epithelial and mesenchymal variants. Am J Surg Pathol 1980;4:451.  

2. Boutin C, Rey F: Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Cancer 1993;72:389-393.

The staging system for malignant pleural mesothelioma is currently being revised by the International Mesothelioma Interest Group (IMIG) and International Association for the Study of Lung Cancer (IASLC).

Referral Information for the New Patient Visit
Patients not previously seen at the BC Cancer Agency may be referred for consultation and management by contacting the Admitting Department of the appropriate regional cancer center. The availability of relevant operative, pathology and imaging laboratory reports will be requested so that these can be obtained prior to the patient being seen, together with the relevant slides and radiographs for review. 

Best Practice Guidelines
All patients with pain require supportive care with aggressive use of analgesics; narcotic analgesics palliate dyspnea as well as pain. Given the restriction in lung function seen in individuals with pleural mesothelioma, strategies to maintain optimum lung function are recommended. Smoking cessation is to be encouraged. Pneumococcal vaccine, and the influenza vaccine when available for the season, should be administered.

Surgery
Patients with stage I mesothelioma are occasionally considered for extrapleural pneumonectomy in conjunction with chemotherapy and radical radiotherapy. Although some patients have been reported to achieve long-term survival with aggressive therapy, such cases are highly selected and it is unclear whether overall survival has been significantly altered by the treatment modalities applied. Mortality from extrapleural pneumonectomy ranges from 6% to 30%. As mesothelioma patients suitable for extrapleural pneumonectomy are rare, such cases should be referred to a thoracic surgeon with experience in performing such operations. Assessment by a multidisciplinary care team including medical and radiation oncologists is also necessary.

Standard surgical therapy for stages I-IV mesothelioma includes drainage of effusions, chest tube pleurodesis, or thoracoscopic pleurodesis. Effusion control may be difficult because of the restrictive nature of the tumour, although regular drainage may be facilitated by insertion of an indwelling pleural catheter. Selected patients may be considered for palliative surgical resection and decortication. Such procedures may provide temporary relief from effusions but there is no established surgical role for palliation of pain associated with chest wall invasion. Operative mortality from pleurectomy/decortication is about 2%.

Radiotherapy 
The role of radical radiotherapy is limited by the volume being treated (the entire hemithorax), the surrounding structures (heart, liver), and the requirement for delivery of a high dose.  It may be planned following extrapleural pneumonectomy.

Palliative treatment of more localized symptomatic areas such as painful areas of the chest wall or involvement of the mediastinum may be feasible.

Chemotherapy
Clinical trials support considering treatment of mesothelioma with chemotherapy.  However, as the rate of disease progression is highly variable, it is reasonable for patients who have few or no symptoms to be managed expectantly. A trial of systemic chemotherapy may be offered to fit patients with symptoms requiring palliation. The probability of benefit is greater in those with epithelioid tumours.

Pemetrexed in combination with a platinum analog is a standard consideration due to the survival benefit seen in a large randomized trial that compared pemetrexed plus cisplatin to cisplatin alone. Alternatives include gemcitabine or raltitrexed in combination with a platinum analog, monotherapy with vinorelbine, or an investigational protocol.

Intracavitary therapy with chemotherapeutic agents (cisplatin, mitomycin or cytarabine), cytokines (interferon), radionuclides, and porphyrin/laser have been reported to induce transient regression of mesothelioma but none of these approaches have demonstrated superiority to supportive care only.

Follow-Up
Mesothelioma patients are generally treated palliatively, and follow-up depends on symptomatology and the treatment modalities used. The BCCA doctor in charge should explicitly clarify the physician in charge of palliative patient follow-up. For patients followed by their referring physicians, the BCCA physicians will act as consultants if requested.

References:

1. Byrne MJ, Davidson JA, Musk AW, et al. Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study. J Clin Oncol 1999; 17: 25-30.

2. Lee CW, Murray N, Anderson H, Rao SC, Bishop W. Outcomes with first-line platinum-based combination chemotherapy for malignant pleural mesothelioma: a review of practice in British Columbia. Lung Cancer 2009; 64: 308-313.

3. Steele JP, Shamash J, Evans MT, Gower NH, Tischkowitz MD, Rudd RM. Phase II study of vinorelbine in patients with malignant pleural mesothelioma. J Clin Oncol 2000; 18: 3912-3917.

4. Tsao AS, Wistuba I, Roth JA, Kindler HL. Malignant pleural mesothelioma. J Clin Oncol 2009; 27: 2087-2090.

5. Vogelzang NJ, Rusthoven JJ, Symanowski 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; 21: 2636-2644.