Malignant pleural mesothelioma remains a lethal disease and its incidence is expected to increase until the 2020’s. Disease extent and performance status at diagnosis are the clinical prognostic factors, besides epithelioid subtype which confers a better outcome than the less common sarcomatoid one. Currently, only administration of palliative chemotherapy has a proven impact on outcome. Treatment of early stage malignant pleural mesothelioma should be offered in a multimodality setting, including at least a systemic and a locoregional treatment. The role of radical surgery remains controversial. Optimal treatment schedules are not defined yet. The standard first line palliative treatment consists of platinum in combination with an antifolate, either pemetrexed or raltitrexed. As the outcome in first line remains modest, it is ethical to include these patients in clinical trials comprising a chemotherapy backbone. For maintenance therapy there’s still no standard in malignant pleural mesothelioma. In second line treatment, referral of patients for inclusion in trials is highly recommended.

(BELG J MED ONCOL 2014;8(5):197–205)