Malignant mesothelioma and asbestos-related lung cancer: diagnosis, prognosis and burden

Abstract

The negative health-related consequences of the use of asbestos have become very clear and widely recognized. This thesis focused on the most frequent asbestos induced cancers: mesothelioma and lung cancer. Mesothelioma A confirmed diagnosis of malignant mesothelioma is important to ensure proper medical care but is also required for patients to initiate a claim for financial compensation. We found that some patients may not obtain compensation when still alive as mesothelioma presence could not be confirmed pathologically, which is the gold standard for mesothelioma. If pathologic material is not sufficient, however, a consensus diagnosis by an expert panel using all available patient information is a valid alternative. To speed up the diagnostic process numerous so-called non-invasive biomarker tests have been developed to facilitate the diagnostic work-up of malignant mesothelioma. To investigate the diagnostic performance of these markers for the detection of malignant mesothelioma a structured review was conducted. We showed that the most frequently studied immunohistochemical markers for cytological analysis were EMA, Ber-Ep4, CEA, and calretinin. The most frequently investigated serum marker was SMRP. However, none of these markers was able to discriminate between malignant mesothelioma and other (lung) diseases. As more treatment options have become available for patients with malignant mesothelioma it is valuable to regularly update survival estimates in patients with malignant mesothelioma. Using a large group of patients with a confirmed diagnosis of malignant mesothelioma we found that only 47% of the patients were still alive one year after diagnosis, 20% after two years and 15% after three years. Prognostic variables independently associated with worse survival were: older age, a specific subtype of the cancer, and a non-pleural localization of the cancer. Asbestos-related lung cancer Exposure to asbestos is known to increase the risk of lung cancer but the exact relationship between exposure and risk is unknown. Particularly at relatively low exposure levels, it is important to estimate the excess risk due to asbestos, as these exposure levels are most frequently seen in The Netherlands. We provided new evidence that at lower asbestos exposure levels the increase in relative risk of lung cancer due to asbestos exposure may be larger than was expected and calculated from previous studies. Finally, we estimated the expected total number of lung cancers due to asbestos exposure in the coming twenty years in the Netherlands using three different, plausible modeling methods. Assumptions and evidence used as input varied widely between these methods. We found that the three modeling methods yield an estimated number of asbestos related lung cancer in the next two decades varying from 6,500 to 22,000 cases. Until more accurate evidence becomes available, the exact impact of asbestos exposure on the lung cancer burden will remain uncertain, but likely between these estimated numbers.