Mesothelioma Guidelines

Updated: Oct 06, 2020
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Guidelines Summary

The following organizations have released guidelines on the diagnosis and treatment of malignant pleural mesothelioma (MPM):

  • American Society of Clinical Oncology (ASCO)
  • National Comprehensive Cancer Network (NCCN)
  • European Society for Medical Oncology (ESMO)
  • British Thoracic Society (BTS)

NCCN guidelines recommend that patients be managed by a multidisciplinary team with experience in MPM. [52]  Treatment options include surgery, radiation therapy (RT), and/or chemotherapy. Select patients may be candidates for multimodality treatment.


All the guidelines recommend the following tests be performed in the initial evaluation and diagnosis of MPM [52, 49, 50, 51] :

  • Chest CT with contrast
  • Thoracentesis for cytologic assessment
  • Pleural biopsy (thoracoscopic biopsy is preferred)

In addition, soluble mesothelin-related peptide (SMRP) measurement is optional and may correlate with disease status, according to NCCN guidelines. [52]

ESMO, ASCO and BTS guidelines concur on the following recommendations for the pathological diagnosis of MPM [49] :

  • Do not rely on cytology alone to make a diagnosis of MPM. If effusion cytology is frankly malignant, the diagnosis may be strongly suggested but confirmation by biopsy, if possible, is recommended. 

  • Immunohistochemistry (IHC) is recommended for the differential diagnosis of MPM in both biopsy and cytology-type specimens.

  • A combination of at least two positive mesothelial (calretinin, cytokeratin 5/6, Wilms tumor 1, D-240) and at least two negative adenocarcinoma immunohistochemical markers (TTF1, CEA, Ber-EP4) should be used in the differential diagnosis of MPM. 

  • MPM should be reported as epithelial, sarcomatoid, or biphasic, because these subtypes have a clear prognostic significance 


NCCN and ASCO concur on the following recommendations for first-line chemotherapy [51, 52] :

  • Chemotherapy should be offered either alone for medically inoperable patients or as part of a multimodality regimen for patients with medically operable disease
  • In asymptomatic patients with epithelial histology and minimal pleural disease who are not surgical candidates, a trial of close observation may be offered prior to the initiation of chemotherapy.
  • First-line chemotherapy of pemetrexed-cisplatin (preferred) or pemetrexed-carboplatin
  • Addition of bevacizumab (Avastin) to pemetrexed-cisplatin in selected patients 
  • Bevacizumab not recommend for patients with significant cardiovascular comorbidity, uncontrolled hypertension, or bleeding/clotting risk.

According to NCCN guidelines other acceptable first-line chemotherapy options include gemcitabine-cisplatin for patients that cannot take pemetrexed. For patients who are not candidates for platinum-based combination therapy, pemetrexed or vinorelbine are first-line treatment options. [52]

NCCN guidelines for second-line treatments recommend pembrolizumab and nivolumab alone or with ipilimumab. Other options include vinorelbine, gemcitabine and pemetrexed if not administered as first-line therapy. [52]

ASCO guidelines offer the following recommendations for second-line chemotherapy [51] :

  • Retreatment with pemetrexed-based chemotherapy may be offered in pleural mesothelioma patients who achieved durable (> 6 months) disease control with first-line pemetrexed-based chemotherapy 
  • Given the very limited activity of second-line chemotherapy, participation in clinical trials is recommended
  • In patients for whom clinical trials are not an option, vinorelbine may be offered 

The ESMO guidelines recommend combination doublet chemotherapy of cisplatin, with either pemetrexed or raltitrexed for patients with unresectable MPM. Carboplatin is an acceptable alternative to cisplatin and may be better tolerated in the elderly population. ESMO finds there is no second-line standard of care. [49]

The BTS guidelines recommend first-line therapy with cisplatin and pemetrexed in patients with good performance status. Raltitrexed is an alternative to pemetrexed. Pemetrexed or vorinostat should not be offered as second-line treatment for patients with MPM. [50]


NCCN and ASCO concur on the following recommendations for surgical treatment of MPM [51, 52] :

  • In selected patients with early-stage disease, pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP) are reasonable surgical options to achieve complete gross cytoreduction.
  • Mediastinal node dissection of at least three nodal stations is recommended in patients undergoing either P/D or EPP. 
  • Maximal surgical cytoreduction as a single modality treatment is generally insufficient; additional antineoplastic treatment (chemotherapy and/or radiation therapy) should be administered.
  • Surgery is not recommended for patients with stage IV disease, saracomatoid or mixed histology. 
  • Surgery is not recommended for patients with N2 disease unless performed at a center of expertise or in a clinical trial.

Radiation Therapy

NCCN guidelines recommend the use of radiation therapy (RT) as part of a multimodality regimen, but RT alone is not recommended for treatment. [52]   Prophylactic RT is not routinely recommended to prevent instrument-tract recurrence after pleural intervention by NCCN guidelines. [52] ASCO guidelines recommend against prophylactic RT but recommend for adjuvant RT for resection of intervention tracts found to be histologically positive. [51]

The BTS recommends against preoperative or postoperative RT, prophylactic radiotherapy to chest wall procedure tracts, and hemithorax RT. [50]  

ESMO guidelines allows RT be given in an adjuvant setting after surgery or chemo-surgery to reduce the local failure rate, however, ESMO found no evidence for its use as a standard treatment. When postoperative RT is applied, strict constraints must be adhered to in order to avoid toxicity to neighbouring organs, and special, tissue sparing, techniques should be used. [49]

All four guidelines recommend RT for palliative therapy to relieve chest pain, bronchial or esophageal obstruction, or symptomatic relief of metastases in the bone or brain.  [49, 50, 51, 52]

In 2019, the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation issued an expert opinion on the use of radiation therapy for the treatment of MPM. The use of the radiation therapy for MPM was recommended in the following scenarios [55] :

  • Before or after extrapleural pneumonectomy;
  • As an adjuvant to lung-sparing procedures (i.e., without pneumonectomy)
  • As palliative therapy for focal symptoms caused by the disease