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NCCN Flash Updates: NCCN Guidelines Updated for Mesothelioma: Pleural and Mesothelioma: Peritoneal

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), The NCCN Radiation Therapy Compendium™, the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), for Mesothelioma: Pleural. These NCCN Guidelines^® are currently available as Version 1.2025.

Link directly to the Updates section of the NCCN Guidelines: Mesothelioma: Pleural

PM-2

• Clinical Assessment
  • Clinical stage I-IIIA changed to Clinical stage I
  • Clinical stage IIIB-IV changed to Clinical stage II–IV and epithelioid histology, sarcomatoid or biphasic histology (any stage)
    • Performance status stratification removed (see new footnote c)
• Treatment
  • Clinical stage I and epithelioid histology
    • New treatment options
      • Systemic therapy and consider pleural IMRT (preferred)
        • Systemic therapy for progression
      • Observation
        • Systemic therapy for progression
• Footnote c added: Best supportive care is recommended for patients presenting with PS 3–4. See Principles of Supportive Care (PM-B).
• Footnote e added: Pleural IMRT should only be performed in carefully selected patients at centers with experience in this technique. See Principles of Radiation Therapy (PM-D).
• Footnote g added: The benefit of surgical resection in pleural mesothelioma is unclear and there is no evidence that patient survival is improved with surgery when combined with systemic therapy versus systemic therapy alone.

PM-3

• This is a new page, replacing the previous PM-3 page.

PM-C 1 of 3

• First-Line Therapy
  • Epithelioid, biphasic or sarcomatoid
    • Cisplatin + gemcitabine changed to (Cisplatin or carboplatin) + gemcitabine
• Footnote removed: Carboplatin is recommended for patients who are not candidates for cisplatin.

PM-C 2 of 3

• Reference 12 added: Favaretto AG, Aversa SML, Paccagnella A, et al. Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study. Cancer 2003;97:2791-2797.

PM-D 1 of 3

• Bullet 6 modified: A randomized phase III trial in patients with non-metastatic pleural mesothelioma who underwent non-radical lung-sparing surgery found substantially greater overall survival with radical hemithoracic sequential pleural intensity-modulated RT (IMRT) compared to palliative RT. Hemithoracic Sequential pleural IMRT after P/D in the presence of an intact lung may be considered in centers with experience and expertise in these methods, given the technical difficulty of this treatment.
• The following bullets were removed:
  • For patients with resectable pleural mesothelioma who undergo EPP, adjuvant RT can be recommended for patients with good performance status (PS) to improve local control.
  • The dose of radiation for adjuvant therapy following EPP should be 45–60 Gy in 1.8–2.0 Gy based on the margin status. A dose of 54 Gy given to the entire hemithorax, the thoracotomy incision, and sites of chest drains was well-tolerated. When it is challenging to deliver 45 Gy, every effort should be made to deliver a minimum dose of 40 Gy.

 

PM-D 2 of 3

• Recommended Doses for Radiation Therapy
  • Treatment type removed: Postoperative after EPP
  • Statement below table removed: After EPP, RT should only be considered for patients who meet the following criteria: ECOG PS ≤1; good functional pulmonary status; good function of contralateral kidney confirmed by renal scan; and absence of disease in abdomen, contralateral chest, or elsewhere. Patients who are on supplemental oxygen should not be treated with adjuvant RT.
• Radiation Techniques
  • Bullet 4: EPP removed.
  • Bullet removed: A minimum technological standard is CT-planned 3D conformal RT (3D-CRT) using photon or photon/electron beams.

PM-D 3 of 3

• References removed:
  • Gupta V, Mychalczak B, Krug L, et al. Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2005;63:1045-1052.
  • Gupta V, Krug LM, Laser B, et al. Patterns of local and nodal failure in malignant pleural mesothelioma after extrapleural pneumonectomy and photon-electron radiotherapy. J Thorac Oncol 2009;4:746-750.
  • Bölükbas S, Manegold C, Eberlein M, et al. Survival after trimodality therapy for malignant pleural mesothelioma: Radical pleurectomy, chemotherapy with cisplatin/pemetrexed and radiotherapy. Lung Cancer 2011;71:75-81.
  • Hasani A, Alvarez JM, Wyatt JM, et al. Outcome for patients with malignant pleural mesothelioma referred for trimodality therapy in Western Australia. J Thorac Oncol 2009;4:1010-1016.
  • Baldini EH, Recht A, Strauss GM, et al. Patterns of failure after trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1997;63:334-338.
  • Rusch VW, Rosenzweig K, Venkatraman E, et al. A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2001;122:788-795.
  • Yajnik S, Rosenzweig KE, Mychalczak B, et al. Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 2003;56:1319-1326.

PM-E

• Bullet 6 modified: For early-stage disease (confined to the pleural envelope, no N2 clinical evidence for lymph node involvement) with favorable histology (epithelioid), P/D may be considered safer than EPP but it is unclear which operation is oncologically better whether there is benefit over systemic therapy alone. There is controversy regarding choice of procedure a decision for surgical resection that needs to be weighed, taking into account tumor histology, distribution, the patient's pulmonary reserve, and availability of adjuvant and intraoperative strategies. P/D and EPP are each reasonable is the preferred surgical treatment options and should can be considered in select patients for complete gross cytoreduction. EPP may be selected in certain cases that require careful consideration of the total treatment plan that includes the patient and multidisciplinary team.

 

NCCN has published updates to the NCCN Guidelines, the NCCN Drugs & Biologics Compendium^®, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™) for Mesothelioma: Peritoneal. These NCCN Guidelines are currently available as Version 1.2025.

Link directly to the Updates section of the NCCN Guidelines: Mesothelioma: Peritoneal

PEM-1

• Initial Evaluation
  • Bullet 1 modified: CT of chest with contrast of chest/ + CT or MRI of abdomen/pelvis with contrast
  • Bullet 5 added: Tumor Ki-67 index
  • Bullet 6 modified: Consider Serum CA-125, Soluble mesothelin-related peptide (SMRP) (optional)
• Differentiation of histology (unicavitary, epithelioid, biphasic/sarcomatoid, bicavitary disease) removed

PEM-2

• This is a new page, replacing the previous PEM-2 and PEM-3 pages.

PEM-A 4 of 8

• Markers as potential prognostic and predictive markers
  • Bullet 1 added: Ki-67 labeling index by IHC staining is independently prognostic for overall survival (OS) for patients undergoing CRS + HIPEC, with Ki-67 index >9% associated with worse survival and is therefore considered a high-risk feature.

PEM-A 7 of 8

• Reference 45 added: Kusamura S, Torres Mesa PA, Cabras A, et al. The role of Ki-67 and precytoreduction parameters in selecting diffuse malignant peritoneal mesothelioma (DMPM) patients for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Ann Surg Oncol 2016;23:1468-1473.

PEM-D 1 of 3

• First-Line Therapy
  • Epithelioid, biphasic or sarcomatoid
    • Cisplatin + gemcitabine changed to (Cisplatin or carboplatin) + gemcitabine
• Footnote removed: Carboplatin is recommended for patients who are not candidates for cisplatin.

PEM-D 2 of 3

• Reference 14 added: Favaretto AG, Aversa SML, Paccagnella A, et al. Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study. Cancer 2003;97:2791-2797.

 

For the complete updated versions of the NCCN Guidelines, NCCN Guidelines with NCCN Evidence Blocks™, the NCCN Drugs & Biologics Compendium (NCCN Compendium^®), the NCCN Biomarkers Compendium^®, the NCCN Chemotherapy Order Templates (NCCN Templates^®), the NCCN Radiation Therapy Compendium™, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC™), please visit NCCN.org.

To view the NCCN Guidelines for Patients^®, please visit NCCN.org/patientguidelines.

Free NCCN Guidelines apps for iPhone, iPad, and Android devices are now available! Visit NCCN.org/apps.

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