**5. Clinical features**

The symptoms of MPM typically present insidiously with vague symptoms [75]. The charac‐ teristic symptoms are pain in half the patients, breathlessness in a third, and constitutional symptoms in less than 10%. At the beginning, symptoms are usually ill-defined and mild, but as the disease progresses, the initial heaviness becomes an ache and pain that interferes with sleep, and the breathlessness would often force the patient to stop working. Medical attention is usually only sought after a median of 3.5 months of progressing symptoms [76].

Physical examination is helpful insofar as suggesting a pleural effusion or pleural thickening, but is nonspecific for the diagnosis of MPM. Peripheral stigmata of pulmonary diseases such as clubbing and hypertrophic pulmonary osteoarthropathy are not features of MPM, and palpable lymphadenopathy is rare.

In those with large effusion, drainage may lead to rapid improvement of symptoms but a trapped lung is also common. As the disease progresses, less fluid is produced and there is progressively more pleural thickening, eventually the fluid disappears and the chest becomes contracted and filled with tumour. Local invasion of the chest wall can result in intractable pain and paresthesia, whilst invasion of the contralateral pleural space, pericardial space or through the diaphragm usually herald a rapid deterioration. Distant spread is common but is usually less symptomatic than the primary site.

The outlook for patients with mesothelioma is bad. For patients who present asymptomatically on a chest radiograph, the median survival is 20 months with best supportive care [76], and it is with this baseline in mind that we should evaluate noncomparative studies on new therapies.
