National Cancer Institute


Expert-reviewed information summary about the treatment of malignant mesothelioma.

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of malignant mesothelioma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Malignant Mesothelioma Treatment

General Information About Malignant Mesothelioma Treatment

Diagnosis and Prognostic Factors

Prognosis in malignant mesothelioma is difficult to assess consistently because there is great variability in the time before diagnosis and the rate of disease progression. In large retrospective series of pleural mesothelioma patients, the following were found to be important prognostic factors:[]

  • Stage.
  • Age.
  • Performance status.
  • Histology.

Prognostic scoring systems

Two prognostic scoring systems have been developed for advanced unresectable mesothelioma and are used to stratify patients enrolling in clinical trials: the Cancer and Leukemia Group B (CALGB) index and the European Organization for the Research and Treatment of Cancer (EORTC) index.

CALGB index

The CALGB index was developed retrospectively using the clinical characteristics of 337 patients treated on clinical trials of chemotherapy for advanced mesothelioma during a 10-year period.[] These characteristics were used collectively to define six prognostic groups with median survivals ranging from 13.9 months (Eastern Cooperative Oncology Group [ECOG] performance status [PS] = 0, age <49 years; or PS = 0, age ≥49 years and hemoglobin ≥14.6g/dL) to 1.4 months (PS = 1 or 2 and white blood cell [WBC] count ≥15.6 × 109/L).

The prognostic value of the CALGB index was evaluated retrospectively in a phase II clinical trial of 105 patients.[] Median survival in this study for patients in the best CALGB prognostic group was 29.9 months compared with 1.8 months for patients in the worst prognostic group. However, the intermediate groups 2 to 4 overlapped in their survival times.

EORTC index

The EORTC index was also developed retrospectively using the characteristics of 181 patients from five phase II clinical trials of chemotherapy during a 9-year period.[] In a multivariate analysis, the following characteristics were associated with poorer survival:

  • WBC count >8.3 × 109/L.
  • ECOG PS ≥1.
  • Unconfirmed histology on central review.
  • Nonepithelioid histology.
  • Male gender.

Patients were allocated a numerical prognostic score based on each of these variables (+0.55 if WBC >8.3 × 109/L, +0.60 if ECOG PS ≥1, +0.52 if unconfirmed histology, and +0.60 if male gender). Subsequently, patients were classified into two prognostic groups that included low-risk patients with a prognostic score of 1.27 or lower (0–2 risk factors) and high-risk patients with a prognostic score higher than 1.27 (3–5 risk factors). High-risk patients had a relative risk of death of 2.9 compared with low-risk patients, < .001; the 1-year survival rate was 40% for the low-risk group compared with 12% for the high-risk group.

Follow-up and Survivorship

Multimodality therapy incorporating radical surgery (extrapulmonary pneumonectomy or radical pleurectomy with decortication) with or without chemotherapy, administered with or without radiation, may be considered for patients with limited disease and has been associated with a relatively long survival in observational series.[] For patients treated with aggressive surgical approaches, factors associated with improved long-term survival include the following:[]

  • Epithelioid histology.
  • Negative lymph nodes.
  • Negative surgical margins.

For patients treated with aggressive surgical approaches, nodal status is an important prognostic factor. Median survival has been reported as 16 months for patients with malignant pleural disease and 5 months for patients with extensive disease. In some instances, the tumor grows through the diaphragm, making the site of origin difficult to assess. Cautious interpretation of treatment results with this disease is imperative because of the selection differences among series. Effusions, both pleural and peritoneal, represent major symptomatic problems for at least 66% of the patients. (Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.)

Carcinogenesis

A history of asbestos exposure is reported in about 70% to 80% of all cases of mesothelioma.

Cellular Classification of Malignant Mesothelioma

Histologically, these tumors are composed of spindle cells (sarcomatoid) or epithelial elements, or both (biphasic). Desmoplastic mesothelioma, consisting of bland tumor cells between dense bands of stroma, is a subtype of sarcomatoid mesothelioma. The epithelioid form is occasionally confused with lung adenocarcinoma or metastatic carcinomas. Epithelioid tumors account for approximately 60% of mesothelioma diagnoses. Attempts to diagnose by cytology or needle biopsy of the pleura are often unsuccessful. It can be especially difficult to differentiate mesothelioma from adenocarcinoma on small tissue specimens. Thoracoscopy can be valuable in obtaining adequate tissue specimens for diagnostic purposes.

Examination of the gross tumor at surgery and use of special stains or electron microscopy can often help to determine diagnosis. Pancytokeratin stains are positive in nearly all mesotheliomas. Particularly useful immunohistochemical stains for the differential diagnosis of epithelioid mesothelioma include cytokeratin 5 and 6, calretinin, WT-1, and D2-40. Calretinin and D2-40 positivity in combination with pancytokeratin positivity is most useful to distinguish sarcomatoid mesothelioma from sarcoma and other histologies. Histologic appearance seems to be of prognostic value, and most clinical studies show that patients with epithelial mesotheliomas have a better prognosis than patients do with sarcomatoid or biphasic mesotheliomas.

Stage Information for Malignant Mesothelioma

Patients with stage I disease have a significantly better prognosis than patients do with advanced stages. Because of the relative rarity of this disease, exact survival information based on stage is limited.

Definitions of TNM

The American Joint Committee on Cancer (AJCC) and International Union Against Cancer (UICC) have designated staging by TNM classification to define malignant mesothelioma.

AJCC and UICC TNM Staging for Diffuse Malignant Pleural Mesothelioma

Treatment Option Overview

Standard treatment for all but localized mesothelioma is generally not curative. Although some patients will experience long-term survival with aggressive treatment approaches, it remains unclear if overall survival (OS) has been significantly altered by the different treatment modalities or by combinations of modalities.

Extrapleural pneumonectomy in selected patients with early-stage disease may improve recurrence-free survival, but its impact on OS is unknown. Pleurectomy and decortication can provide palliative relief from symptomatic effusions, discomfort caused by tumor burden, and pain caused by invasive tumor. (Refer to the PDQ summary on Cancer Pain for more information.) Trimodality therapy refers to a combination of chemotherapy, definitive surgery, and radiation therapy. Because of the rarity of mesothelioma and the complexities of patient selection, surgical technique, and optimal sequencing of therapy, delivery of such therapy in centers with medical personnel who have established experience and expertise in the management of mesothelioma has shown better results. Operative mortality from pleurectomy with decortication is less than 2%, while mortality from extrapleural pneumonectomy has ranged from 6% to 30%.

Several single-arm, phase II studies have demonstrated prolonged survival times (compared with historic controls) for selected patients who received adjuvant radiation therapy after definitive surgery. The use of radiation therapy in pleural mesothelioma has also been shown to alleviate pain in the majority of patients treated; however, the duration of symptom control is short-lived. Other single-arm, phase II studies investigated neoadjuvant chemotherapy (mainly with platinum and pemetrexed or gemcitabine) followed by definitive surgery followed by adjuvant radiation. These studies have also shown prolonged survival compared with historical controls; however, this advantage has yet to be confirmed in a randomized study.

Localized Malignant Mesothelioma (Stage I)

Standard treatment options:

Treatment options under clinical evaluation:

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with localized malignant mesothelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Advanced Malignant Mesothelioma (Stages II, III, and IV)

Standard treatment options:

Information about ongoing clinical trials is available from the NCI website.

Treatment trials for advanced malignant mesothelioma

Malignant Peritoneal Mesothelioma

A multi-institutional registry study evaluated cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse, malignant, peritoneal mesothelioma. Among 401 patients, 187 (46%) had complete or near-complete cytoreduction, and 372 (92%) received HIPEC. Of the HIPEC patients, 311 (83%) received cisplatin and doxorubicin. The median follow-up period was 33 months (range, 1–235 months). Grade 3 to 4 complications were seen in 127 (31%) of the 401 patients, and 9 patients (2%) died perioperatively.

The mean length of hospital stay was 22 days (standard deviation, 15 days). The overall median survival was 53 months (1–235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis:

  • Epithelial subtype ( < .001).
  • Absence of lymph node metastasis ( < .001).
  • Completeness of cytoreduction (CC) scores of CC-0 or CC-1 ( < .001).
  • HIPEC ( = .002).

This kind of analysis is subject to the biases of strong patient selection.

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with advanced malignant mesothelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Recurrent Malignant Mesothelioma

Treatment of patients with recurrent malignant mesothelioma usually utilizes procedures and agents not previously employed in the initial treatment attempt. No standard treatment approaches have been proven to improve survival or control symptoms for a prolonged period. Selected patients with localized disease recurrence may be candidates for additional chest wall resection. One trial of 47 carefully selected patients at a single institution indicated that chest wall resection could be safely performed; time-to-recurrence from initial resection appeared to be predictive of expected survival benefit and gets factored into decision-making.[]

Patients with recurrence are candidates for phase I and II clinical trials evaluating new targeted therapies, biologicals, chemotherapeutic agents, or physical approaches. Patients with recurrent malignant mesothelioma who have not received chemotherapy previously are candidates for first-line chemotherapy with cisplatin pemetrexed or cisplatin raltitrexed. (Refer to the Advanced Malignant Mesothelioma (Stages II, III, and IV) section of this summary for more information.) However, patients with recurrent malignant mesothelioma who undergo surgery, or at least do not receive chemotherapy as part of the primary treatment and whose disease recurs subsequently, are candidates for chemotherapy.

A large randomized study compared pemetrexed with best supportive care in 243 patients who received one previous regimen of chemotherapy that did not include pemetrexed.[] No survival benefit was shown in patients who received pemetrexed, although the progression-free survival rate, time-to-progression, and the response rates favored the pemetrexed arm.

Current Clinical Trials

Check the list of NCI-supported cancer clinical trials that are now accepting patients with recurrent malignant mesothelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Changes to This Summary (10/14/2016)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Advanced Malignant Mesothelioma (Stages II, III, and IV)

Revised text in a standard treatment option to state that first-line combination chemotherapy with cisplatin, pemetrexed, and bevacizumab showed improved survival compared with single-agent cisplatin (cited Zalcman et al. as reference 7).

Added text to state that a randomized, controlled, open-label, phase III trial evaluated the addition of bevacizumab to chemotherapy and showed an improved overall survival with the three-drug regimen. Also added that the trial included 448 patients with unresectable malignant pleural mesothelioma who were randomly allocated to receive intravenous pemetrexed plus cisplatin with or without bevacizumab in 21-day cycles for up to six cycles, until progression or toxic effects were seen; statistical data related to survival outcomes and adverse events were included (added level of evidence1iiA).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of malignant mesothelioma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Malignant Mesothelioma Treatment are:

  • Janet Dancey, MD, FRCPC (Ontario Institute for Cancer Research & NCIC Clinical Trials Group)
  • Patrick Forde, MD (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins)
  • Raymond Mak, MD (Harvard Medical School)
  • Eva Szabo, MD (National Cancer Institute)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Malignant Mesothelioma Treatment. Bethesda, MD: National Cancer Institute. Updated . Available at: http://www.cancer.gov/types/mesothelioma/hp/mesothelioma-treatment-pdq. Accessed . [PMID: 26389420]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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