Mesothelioma: Definition and Prognosis
Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural lining with a poor prognosis of approximately 1 year median survival; cure is rare and outcomes depend primarily on disease stage, histological subtype, and patient performance status.
Definition and Epidemiology
- MPM is the most common type of mesothelioma, affecting the lining of the lungs and chest wall 1
- Incidence is approximately 2,500 cases annually in the United States 1
- Strong association with asbestos exposure (70-80% of cases), with a long latency period of 20-40 years after exposure 1
- Incidence is expected to peak within the next decade in many countries 1
- More common in older men (median age at diagnosis: 72 years) 1
Clinical Presentation
- Common symptoms include:
- Dyspnea (shortness of breath) due to pleural effusion
- Chest pain (especially in advanced stages)
- Pleural effusion
- Fatigue, insomnia, cough
- Chest wall mass
- Loss of appetite and weight loss 1
Diagnosis
- Thoracoscopy is recommended for diagnosis except when contraindicated 1
- Multiple biopsies (at least 10 samples from multiple sites) of adequate size (≥4mm) should be taken 1
- Immunohistochemistry is essential for diagnosis, including:
- For epithelioid tumors: cytokeratin (CK 5/6), EMA, calretinin
- For spindle cell tumors: cytokeratin, vimentin, CD34 1
- CT scan of chest is the standard examination to assess tumor extent 1
- FDG PET/CT is recommended for comprehensive initial staging 2
Histological Subtypes
Three main histological types:
- Epithelioid (most common, 60% of cases) - best prognosis
- Sarcomatoid - worst prognosis
- Biphasic (mixed) - intermediate prognosis 1
Staging and Prognosis
Prognostic Factors
The three most important favorable prognostic factors are:
- Early disease stage (I or II)
- Epithelioid histology
- Good performance status (0 or 1) 1
Median Survival
- Overall median survival: approximately 1 year 1
- Range: 6-18 months depending on prognostic factors 1
- 5-year survival rate is only about 11%, even with careful patient selection 1
Poor Prognostic Indicators
- Sarcomatoid or mixed histology
- Thrombocytosis
- Fever of unknown origin
- Age >65 years
- Poor performance status
- Advanced stage disease 1
Treatment Approaches
MPM is difficult to treat and requires a multidisciplinary team with experience in MPM management 1, 2.
Surgery
- Surgical options include:
- Extrapleural pneumonectomy (EPP) - not recommended for sarcomatoid histology
- Pleurectomy/decortication (P/D) - may be indicated in early stages
- Selection criteria for surgery: good performance status, early-stage disease without mediastinal lymph node involvement, epithelioid histology 1
- Surgery alone has not been validated as a standard treatment 1
Chemotherapy
- First-line therapy for unresectable disease: cisplatin/pemetrexed (Category 1 recommendation) 1
- Bevacizumab/cisplatin/pemetrexed is also recommended as first-line therapy for eligible patients 1, 2
- Pemetrexed is FDA-approved for malignant pleural mesothelioma in combination with cisplatin 3
Radiotherapy
- Limited use due to side effects on underlying lung
- Can be used for palliative pain management
- Prophylactic irradiation of drain sites and puncture sites is recommended 1
Multimodality Approach
- For select patients with clinical stages I-III who are medically operable with good performance status 1
- May include combinations of surgery, chemotherapy, and radiotherapy
- Should be performed at specialized centers 1
Palliative Care
- Important due to high symptom burden 1, 2
- Management of pleural effusions through pleurodesis or pleurectomy 1
- Early pleurodesis is recommended if intracavitary treatment is not planned 1
Follow-up and Monitoring
- Response evaluation using CT scan with modified RECIST criteria is recommended after 2-3 chemotherapy cycles 1, 2
- Regular imaging follow-up to assess disease progression 2
Mental Health Impact
- MPM has significant mental health impacts including traumatic stress, depression, anxiety, and guilt 4
- Patients report lack of access to mental health support 4
MPM remains a challenging disease with limited treatment options and poor outcomes. The prognosis is heavily dependent on disease stage, histological subtype, and patient performance status, with epithelioid histology and early-stage disease offering the best chances for longer survival.