Staging of Pleural Mesothelioma
Use the 8th revision of the UICC TNM staging system for all clinical and pathological staging of malignant pleural mesothelioma. 1
TNM Staging Classification
The International Mesothelioma Interest Group (IMIG) TNM staging system stratifies patients into four distinct prognostic categories 1:
Stage I
- Stage Ia (T1a N0 M0): Primary tumor limited to ipsilateral parietal pleura 1
- Stage Ib (T1b N0 M0): Stage Ia plus focal involvement of visceral pleura 1
Stage II
- T2 N0 M0: Stage Ia or Ib plus confluent involvement of diaphragm or visceral pleura, or involvement of the lung parenchyma 1
Stage III
- Any T3 M0: Locally advanced tumor 1
- Any N1 M0: Ipsilateral bronchopulmonary or hilar lymph node involvement 1
- Any N2 M0: Subcarinal or ipsilateral mediastinal lymph node involvement (note: in the 8th edition, hilar and mediastinal nodes are now classified as N1, with contralateral or extra-thoracic nodes as N2) 1
Stage IV
- Any T4: Locally advanced technically unresectable tumor 1
- Any N3: Contralateral mediastinal, internal mammary, and ipsilateral or contralateral supraclavicular lymph node involvement 1
- Any M1: Distant metastases 1
Staging Investigations
For All Patients Fit for Active Treatment
- Contrast-enhanced CT of chest and upper abdomen is the baseline imaging modality for diagnosis and staging 1
- Evaluate patient age, performance status, and physiological functioning before extensive staging to determine tolerance for active therapy 1
For Surgical Candidates Considered for Multimodality Therapy
- PET-CT should be performed to exclude occult distant metastatic disease and assess prognostic utility of maximum standard uptake values 1
- PET-CT should ideally be obtained before pleurodesis, as talc causes pleural inflammation leading to false-positive FDG avidity 1
- Mediastinoscopy or endobronchial ultrasound (EBUS) fine-needle aspiration of mediastinal lymph nodes is recommended if surgical resection is being considered 1
- Mediastinoscopy is specifically recommended when potential resectable disease exists and EBUS is negative despite FDG-avid lymph nodes 1
- Laparoscopy may be performed to rule out transdiaphragmatic extension, as peritoneal extension indicates stage IV unresectable disease 1
- Chest MRI may be useful for specific surgical questions regarding chest wall, diaphragm, or lung parenchyma infiltration 1
- Brain imaging is not routine but should be considered if clinical suspicion exists, though central nervous system involvement in early-stage disease is very rare 1
Pulmonary Function Assessment for Surgical Candidates
- Pulmonary function tests are required 1
- Perfusion scanning if FEV1 < 80% 1
- Cardiac stress tests to exclude significant cardiac disease 1
Critical Staging Pitfalls
Understaging is common with PET-CT, as accurately staging patients before surgery is difficult 1. However, PET-CT remains useful for determining metastatic disease presence 1.
N2 nodal disease is more frequent than previously reported, with 50% of patients having N2 disease in surgical series 2. The 8th edition now classifies hilar and mediastinal nodes as N1, with contralateral or extra-thoracic nodal metastases as N2 1.
Most patients present with locally advanced disease at diagnosis 1. The median survival ranges from 6-18 months from diagnosis 3.
Pathological Staging Considerations
Pathological staging should be limited to macroscopic complete resection (MCR) specimens, with smaller specimens being clinically staged 1. Clear marking of the surgical specimen is critical for accurate pathological staging due to well-documented survival differences between pT3 and pT4 tumors 1. Resection of previous biopsy or incision sites has prognostic importance, as does resected tumor weight 1.
Prognostic Factors Beyond TNM Stage
Histologic type is a critical prognostic factor: epithelioid subtype has better survival, while sarcomatoid subtype has the worst prognosis 1, 3, 2. The European Organization for Research and Treatment of Cancer prognostic scores include performance status, gender, certainty of histology, histological type, and white blood count 1.
Additional poor prognostic factors include age >65 years, presence of chest pain, weight loss, and fever of unknown origin 3.