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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:[1,2][Level of evidence: 3iiiA]
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.
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.[Level of evidence: 3iiiA] 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 ≥14.6 g/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.[Level of evidence: 3iii] 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.
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.[Level of evidence: 3iiiA] In a multivariate analysis, the following characteristics were associated with poorer survival:
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, P < .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.[Level of evidence: 3iiiA] For patients treated with aggressive surgical approaches, factors associated with improved long-term survival include the following:[7,8][Level of evidence: 3iiiD]
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.)
A history of asbestos exposure is reported in about 70% to 80% of all cases of mesothelioma.[1,9,10]
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 in 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.[3,4,5]
American Joint Committee on Cancer (AJCC) Stage Groupings and Definitions of TNM
The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define malignant mesothelioma.
Cancers staged using the AJCC cancer staging system include classifications for diffuse malignant pleural mesotheliomas but do not include localized malignant pleural mesotheliomas or other primary tumors of the pleura.
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.
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%.[1,3]
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.[2,4,5] 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.[6,7] Other single-arm, phase II studies investigated neoadjuvant chemotherapy (mainly with platinum and pemetrexed or gemcitabine) followed by definitive surgery followed by adjuvant radiation.[8,9,10] These studies have also shown prolonged survival compared with historical controls; however, this advantage has yet to be confirmed in a randomized study.
Standard Treatment Options for Localized Malignant Mesothelioma (Stage I)
Standard treatment options for localized malignant mesothelioma (stage I) include the following:
Treatment Options Under Clinical Evaluation for Localized Malignant Mesothelioma (Stage I)
Treatment options under clinical evaluation for localized malignant mesothelioma (stage I) include the following:
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Standard Treatment Options for Advanced Malignant Mesothelioma (Stages II, III, and IV)
Standard treatment options for advanced malignant mesothelioma (stages II, III, and IV) include the following:
Information about ongoing clinical trials is available from the NCI website.
Treatment Options Under Clinical Evaluation for Advanced Malignant Mesothelioma (Stages II, III, and IV)
Treatment options under clinical evaluation for advanced malignant mesothelioma (stages II, III, and IV) include the following trials:
After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxic effects.
Dexamethasone (4 mg) or an equivalent corticosteroid was administered orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose.
Combination immune checkpoint inhibitor therapy may be considered as an alternative to combination chemotherapy.
Malignant Peritoneal Mesothelioma
Malignant peritoneal mesothelioma arises from the mesothelial cells of the peritoneum and spreads within the confines of the abdominal cavity. There have been few prospective clinical trials conducted in this patient population. Most clinical evidence arises from single-center retrospective studies. Male sex and sarcomatoid or biphasic subtype disease are correlated with poor prognosis.[18,19]
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are offered to patients with diffuse malignant peritoneal mesothelioma, no extraperitoneal disease spread, a good performance status, and those predicted to achieve complete surgical cytoreduction. Among centers with expertise in this form of therapy, reported median survival for appropriately selected patients approaches 3 to 4 years.[18,19]
In patients with malignant peritoneal mesothelioma, efficacy of pemetrexed plus cisplatin appeared comparable to that seen in pleural mesothelioma, and was been well tolerated. Prospective phase II or III clinical trials of this regimen have not been conducted in patients with peritoneal mesothelioma.
Carboplatin may be substituted for cisplatin.
The pemetrexed/cisplatin/bevacizumab and nivolumab/ipilimumab regimens that improved OS were conducted exclusively in patients with malignant pleural mesothelioma, and data to support the efficacy and safety of these regimens in patients with malignant peritoneal mesothelioma are required.
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 improved 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 is factored into decision-making.[Level of evidence: 3iiiA]
Patients with recurrence are candidates for phase I and II clinical trials evaluating new targeted therapies, biologicals, chemotherapeutic agents, or physical approaches.[2,3,4,5,6,7,8,9] Patients with recurrent malignant mesothelioma who have not received chemotherapy previously are candidates for first-line chemotherapy with cisplatin and pemetrexed or cisplatin and raltitrexed. (Refer to the Advanced Malignant Mesothelioma [Stages II, III, and IV] Treatment section of this summary for more information.) However, patients with recurrent malignant mesothelioma who undergo surgery, or who 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.[Level of evidence: 1iiA] 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.
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) Treatment
Added first-line nivolumab and ipilimumab as a standard treatment option for advanced malignant mesothelioma.
Added text about CheckMate743, an open-label, randomized, phase III study that randomly assigned 605 patients with advanced treatment-naive pleural mesothelioma to receive either nivolumab and ipilimumab or chemotherapy; nivolumab plus ipilimumab significantly extended overall survival (cited Baas et al. as reference 6 and level of evidence 1iiA).
Added text to state that combination immune checkpoint inhibitor therapy may be considered as an alternative to combination chemotherapy.
The Malignant Peritoneal Mesothelioma subsection was extensively revised.
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.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult 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:
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 (Adult) are:
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.
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The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Malignant Mesothelioma Treatment (Adult). Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/mesothelioma/hp/mesothelioma-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389420]
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Last Revised: 2021-03-26
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