Malignant mesothelioma

What is malignant mesothelioma?

Malignant mesothelioma is an aggressive tumour of mesothelial cells which usually occurs in the pleura (80-90% of all cases) but also at other sites, including the peritoneum, pericardium and testes. Malignant pleural mesothelioma rarely metastasises to distant sites but most patients present with locally advanced disease. Patients with asbestos-related mesothelioma may be entitled to compensation.¹

How common is malignant mesothelioma? (Epidemiology)

• Malignant mesothelioma is a rare malignancy. It is three times more common in men than in women.

• Almost half (47%) of cases of mesothelioma are diagnosed in people aged 75 and over.²

• The incidence of malignant pleural mesothelioma in males in the UK is 3.4 per 100,000. There are around 2,700 new cases in the UK each year.²

• The incidence continues to rise because of the long lag time between exposure and diagnosis and the relatively recent ban on asbestos use.³

• Malignant pleural mesothelioma has an increasing incidence in industrialised countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease.⁴

• The latent period between exposure and development of the tumour may be up to 50 years.³

• The number of deaths from mesothelioma in the UK rose from 153 in 1968 to around 2,400 people in 2012.² The incidence of mesothelioma is expected to peak at around 2020 and then to decline rapidly.

• Occupational exposure to asbestos accounts for more than 80% of cases, but only 20% of patients also have pulmonary asbestosis.³

Malignant mesothelioma symptoms presentation⁵

• Shortness of breath, chest pain and weight loss are the most common symptoms.

• Malignant mesothelioma should be considered in any patient with a pleural effusion or pleural thickening, especially if a history of asbestos exposure and chest pain is present.

• Chest pain is typically dull, diffuse, progressive. It can occasionally be pleuritic.

• Breathlessness may be caused by a pleural effusion or circumferential pleural thickening.

• Patients may also present with a palpable chest wall mass.

• Fatigue, fever and sweats may occur.

• Finger clubbing is usually caused by underlying asbestosis.

• Pericardial effusion may be caused by local extension in progressive disease. Ascites caused by peritoneal mesothelioma and secondary hydropneumothorax are uncommon but recognised presentations.

• If the tumour has metastasised there may be lymphadenopathy, hepatomegaly, bone pain, bone tenderness, abdominal pain and gastrointestinal obstruction (peritoneal malignant mesothelioma).

Investigations³

• CXR and CT scan with contrast:⁶ may show a pleural effusion, lobulated or nodular pleural thickening, a pleural mass and rib destruction; other features of exposure to asbestos may also be present.

• MRI and positron emission tomography (PET) scans may also be performed.

• Pleural fluid: straw-coloured or bloodstained. Cytological analysis occasionally leads to the diagnosis but a pleural biopsy is usually required.

• Pleural biopsy: ultrasound or CT-guided percutaneous biopsy.

• Mediastinoscopy and video-assisted thoracoscopy may be useful in determining the stage. Thoracoscopy under local anaesthetic (enabling drainage of pleural fluid, pleural biopsy and pleurodesis) is often undertaken.

Associated diseases

See the separate Asbestos-related Diseases article. Inhalation of asbestos fibres can lead to benign pleural disease (pleural plaques, diffuse pleural thickening, atelectasis), parenchymal lung disease (asbestosis) and malignant chest disease (mesothelioma, lung cancer).

Staging³

• Stage Ia:
  

  • T1a N0 M0: primary tumour limited to ipsilateral parietal pleura.

• Stage Ib:
  

  • T1b N0 M0: as stage Ia plus focal involvement of visceral pleura.

• Stage II:
  

  • T2 N0 M0: as stage Ia or Ib plus confluent involvement of diaphragm or visceral pleura or involvement of the lung.

• Stage III:
  

  • Any T3 M0: locally advanced tumour.

  • Any N1 M0: ipsilateral, bronchopulmonary or hilar lymph node involvement.

  • Any N2 M0: subcarinal or ipsilateral mediastinal lymph node involvement.

• Stage IV:
  

  • Any T4: locally advanced technically unresectable tumour.

  • Any N3: contralateral mediastinal, internal mammary, and ipsilateral or contralateral supraclavicular lymph node involvement.

  • Any M1: distant metastases.

Malignant mesothelioma treatment and management

Symptomatic, as cure is usually only possible with surgery for extremely localised (stage I) mesothelioma. The role and order of adjuvant or neoadjuvant use of chemotherapy, immunotherapy, radiotherapy and surgery is recommended in 2021 ESMO guidelines treatment algorithm.³

Surgery

• The role of surgery is important in the diagnosis, staging and treatment of mesothelioma.

• The role of surgery is controversial but extrapleural pneumonectomy and lung-sparing debulking procedures may be considered.

• The best survival data are reported from groups using multimodality treatment including macroscopic complete resection (MCR) achieved by either extrapleural pneumonectomy (EPP) or extended pleurectomy/decortication.⁷

• Pleurectomy and decortication may provide palliative relief from pain and pleural effusions.

Chemotherapy

• Chemotherapy has been shown to improve survival of patients with unressectable mesothelioma.⁸

• Platinum-based chemotherapy remains the cornerstone of treatment.⁹

• Several classes of drugs are being explored either in combination with cisplatin and pemetrexed or as single agent for relapsed or progressive malignant pleural mesothelioma.¹⁰

• Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of therapeutic strategies, including molecular targeted approaches - for example, with the inhibition of vascular endothelial growth factor bevacizumab, with immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses.³ These can be used alone or combined with other systemic therapy for first-line treatment of MPM.

Radiotherapy

• There is still much debate about whether a scar after thoracoscopy and/or drainage procedures should be irradiated prophylactically in order to reduce the likelihood of seeding metastases.³

• For some patients, radiotherapy may be given in an adjuvant setting after surgery or chemo-surgery to reduce the local failure rate. ³ However, there is little good evidence to support this practice.

• Radiotherapy for pain control in patients is an effective treatment in a proportion of patients.¹¹

Prognosis⁶

• The survival of patients with malignant pleural mesothelioma remains poor and typically around one year.^{12 6}

• It depends on the patient's age, staging information, histology and general performance status at diagnosis but is generally very poor.

• 10 year+ survival in England (2013-2017) is 2%.²