FORUM EKSPERTÓW
Mesothelioma and Radical Surgery (MARS): a randomised controlled trial of extrapleural pneumonectomy for malignant pleural mesothelioma

For many surgical interventions the benefits of surgery are self evident. These interventions can be characterised as having a clear mechanistic role in dealing with the problem: the surgical intervention which we employ clearly alters the course of events and corrects the problem. Thus in tension pneumothorax, relief of valvular stenosis, hip replacement, cataract surgery or the simple Thomas’s splint for femoral fracture it is easy to distinguish the signal from the noise and reasonable people need no further persuasion [1]. Then we do not need randomised trials [2, 3].

In contrast in malignant pleural mesothelioma there is characteristically a long interval between the initiating asbestos exposure and the insidious first manifestations of the disease, and there is a variable course thereafter. After Butchart’s work published 35 years ago [4] there was little take up of radical surgery; it was the results when the surgery was combined with chemotherapy which raised hopes once more [5]. From that time on it became increasingly difficult to see the signal from the noise. There was increasing knowledge about which cases survived longer after surgery [6] but whether survival was due to the selection as opposed to the intervention was unproven. Chemotherapy has been shown to improve survival in a randomised controlled trial [7] and when surgery and chemotherapy are combined, the effect of the surgery itself can no longer be clearly discerned. The “signal” of surgery cannot be distinguished from the “noise” of other therapies amongst the highly selected subset of patients put forward for operation. But results were not noticeably improving over time. The median survival in the Brigham and Women’s series published in 2009 [8] was only 13 months – six months shorter than the survival of 19 months which raised hopes for some in 1999 [6]. In so far as one can make uncontrolled comparisons surely this should have signalled that things were heading in the wrong direction.

Thirty five years after the first series of extirpative operations for malignant pleural mesothelioma undertaken in the hope of cure [4] it was pointed out eloquently by Rena and Casadio that belief in cure flies in the face of the clinical evidence gained from years of experience with this disease [9]. Not only, as they argued, had their been no demonstrable cases of cure, and this is after a large number of surgical follow up studies [10] but the operation has...


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