GENERAL INFORMATION

Prognosis in this disease is difficult to assess consistently because there is great variability in the time before diagnosis and the rate of disease progression. Various surgical procedures may be possible in selected patients, providing long-term survival without cure. In large retrospective series of pleural mesothelioma patients, important prognostic factors were found to be stage, age, performance status, and histology.[1,2] For patients treated with aggressive surgical approaches, factors associated with improved long-term survival include epithelial histology, negative lymph nodes, and negative surgical margins.[3,4] For those patients treated with aggressive surgical approaches, nodal status is an important prognostic factor.[3] Median survival for malignant local pleural disease has been reported as 16 months, and extensive disease as 5 months. In some instances the tumor grows through the diaphragm making site of origin difficult to assess. Cautious interpretation of treatment results in this disease is imperative because of the selection differences among series. Effusions, both pleural and peritoneal, represent major symptomatic problems for at least two thirds of the patients. A history of asbestos exposure is reported in about 70%-80% of all cases of mesothelioma.

CELLULAR CLASSIFICATION

STAGE INFORMATION

Patients with stage I disease have a significantly better prognosis than those with more advanced stages. However, because of the relative rarity of this disease, exact survival information based upon stage is limited. proposed staging system based upon thoracic surgery principles and clinical data is shown below.It is a modification of the older system proposed by Butchart et al.[ Other staging systems that have been employed, including a proposed new international TNM staging system, are summarized by the International Mesothelioma Interest Group.

Stage I: Disease confined within the capsule of the parietal pleura: ipsilateral pleura, lung, pericardium, and diaphragm

Stage II: All of stage I with positive intrathoracic (N1 or N2) lymph nodes

Stage III: Local extension of disease into the following: chest wall or mediastinum; heart or through the diaphragm, peritoneum; with or without extrathoracic or contralateral (N3) lymph node involvement

Stage IV: Distant metastatic disease

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 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 overall survival is unknown.[1] Pleurectomy and decortication can provide palliative relief from symptomatic effusions, discomfort caused by tumor burden, and pain caused by invasive tumor. Operative mortality from pleurectomy/decortication is less than 2%,[2] while mortality from extrapleural pneumonectomy has ranged from 6% to 30%.[1,3] The addition of radiation therapy and/or chemotherapy following surgical intervention has not demonstrated improved survival.[2] The use of radiation therapy in pleural mesothelioma has been shown to alleviate pain in the majority of patients treated. However, the duration of symptom control is short-lived.[4,5] Single agent and combination chemotherapy have been evaluated in single and combined modality studies. The most studied agent is doxorubicin, which has produced partial responses in approximately 15%-20% of patients studied.[6] Some combination chemotherapy regimens have been reported to have higher response rates in small phase II trials. However the toxicity reported is also higher and there is no evidence that combination regimens result in longer survival or longer control of symptoms.[6,7]. Recurrent pleural effusions may be treated with pleural sclerosing procedures; however, failure rates are high secondary to the restrictive nature of the tumor.

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.

LOCALIZED MALIGNANT MESOTHELIOMA (STAGE I)

Treatment options:[1]

Standard:

1. Solitary mesotheliomas: Surgical resection en bloc including contiguous structures to ensure wide disease-free margins. Sessile polypoid lesions should be treated with surgical resection to ensure maximal potential for cure.[2]
2. Intracavitary mesothelioma: A. Palliative surgery (pleurectomy and decortication) with or without postoperative radiation therapy B. Extrapleural pneumonectomy C. Palliative radiation therapy

Under clinical evaluation:

ADVANCED MALIGNANT MESOTHELIOMA (STAGES II, III, AND IV)

Treatment options: