Randomised controlled trials of proton beam therapy are needed

Epstein questions whether the investment of £250m (€307m; $405m) in two NHS UK proton facilities is premature.1 The ability of protons to confine the high dose volume to the tumour while minimising the dose to adjacent normal tissues is theoretically attractive in, for example, selected paediatric intracranial tumours, skull based cancers, and prostate tumours. However, the evidence for the clinical efficacy of protons is weak and based mainly on uncontrolled studies,2 3 which are potentially subject to selection bias. The absence of evidence from randomised controlled trials makes the assessment of cost effectiveness difficult, and it is largely based on modelling exercises.4 The lack of such trials partly reflects doctors’ reluctance to enter patients into trials comparing protons and photons because of the perceived superiority of protons.

In the 1980s it was unclear whether fast neutrons improved the therapeutic ratio in hypoxic tumours, such as head and neck cancers. The higher radiobiological effectiveness of neutrons compared with photons offered a theoretical advantage. However, the Edinburgh randomised trial comparing fast neutrons and photons showed that local control was similar but late severe morbidity from radiation was significantly higher in patients treated with neutrons.5 With the projected 1500 patients a year to be referred for proton therapy, the UK should rigorously evaluate the clinical efficacy and toxicity of protons in adequately powered randomised controlled trials. Only then will we know whether proton therapy is a real clinical advance.