Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an uncommon tumor with approximately 2000 to 3000 new cases diagnosed in United States each year. The incidence varies from 13 to 33 to 66 per million per year in the United States, South Africa, and Western Australia, respectively. Between 1940 and 1970, there has been a steady increase in the incidence due to occupational exposure to asbestos, and is expected to peak somewhere between 1990 and 2010. However, additional factors are likely to contribute to the development of this malignancy, since approximately 20% of patients who develop MPM have no history of asbestos exposure. Regardless of its cause, the natural history of MPM is one of locoregional progression of disease with the ultimate development of distant metastases. Despite aggressive multimodality therapy, the median survival of patients diagnosed with this disease ranges from 9 months to 20 months. The association of asbestos with MPM was first recognized by Wagner et al. and confirmed by others. Asbestos fibers lodged in the respiratory bronchioles and alveoli promote alveolar inflammation, interstitial pneumonitis, and eventual fibrosis, resulting in the clinical syndrome of asbestosis. The fibers are also conveyed to the pleural space by subpleural lymphatics where chronic inflammation and subsequent fibrosis form parietal pleural plaques. Such plaques can transform into malignant mesothelioma. Initially manifesting as small nodules, they coalesce and ultimately invade adjacent structures such as the visceral pleura, mediastinum, pericardium, and diaphragm. The tumor is notorious for its nonspecific presentation and extensive local infiltration. Diagnosis is often delayed by 2 months and even beyond 6 months in a quarter of patients. Overall median survival of unresected patients ranges from 7 to 11 months, with more than 80% of patients succumbing to local disease rather than metastatic spread. While the natural history of this debilitating disease is well recognized, treatment options are limited and controversial. In addition, there is no “standard” therapy in the management of patients with this disease. Surgery, radiation therapy, chemotherapy, and immunotherapy have all been used with varying success. More recently, multimodality treatment regimens have combined surgery with adjuvant radiation therapy and chemotherapy. However, most patients with this disease have been treated in an individualized manner, and this has hampered the ability to accurately identify factors of prognostic significance. Despite the limitations just described, earlier retrospective and recent prospective studies have identified prognostic variables using univariate and multivariate analyses of large groups of patients with MPM. These factors can be broadly grouped into clinical and pathologic factors. Clinical factors associated with a favorable prognosis include: (1) age less than 65, (2) absence of chest pain, (3) long duration of symptoms, (4) weight loss of less than 5% at presentation, (5) good performance status, and (6) a normal platelet count. Surgical–pathologic factors include (1) epithelial histology, (2) absence of nodal metastases, (3) early surgical–pathologic stage, and (4) complete resection. Although some of the clinical factors identified by univariate analysis lose their statistical significance when evaluated by multivariate analysis, they remain important because they often serve to identify patients with advanced disease who are unlikely to benefit from aggressive multimodality therapy. Keywords: stage; histologic type; age; weight loss; ECOG performance status; completeness of resection; symptoms; gender