Research in context
Evidence before this study
We searched PubMed between Jan 1, 2000, and Dec 31, 2006, when the HYPRO trial design was completed, with the terms “prostate” AND (“randomized trial” OR “randomised trial”) AND (“hypofractionated” OR “hypofractionation”). We retrieved published reports of three randomised phase 3 trials, mostly of low radiotherapy treatment doses by current standards. The suggested low α/β ratio for prostate cancer clearly showed a need for additional, large, randomised hypofractionation trials to test the predicted increase in radiobiological tumour dose using hypofractionated radiotherapy. The aim of the HYPRO trial was to show superiority of hypofractionation compared with conventional fractionation in terms of relapse-free survival.
Added value of this study
The hypofractionated treatment regimen used in this trial (19 fractions of 3·4 Gy) was not superior to conventional treatment (39 fractions of 2·0 Gy) with respect to relapse-free survival. The postulated superiority of hypofractionation was based on calculations with the linear quadratic model, assuming an α/β ratio for prostate cancer of 1·5 Gy. Results of the HYPRO trial accord with those of other studies and, therefore, raise questions about the actual α/β ratio for prostate cancer, which might be higher than originally predicted. However, frequent use of long-term (>12 months) androgen deprivation therapy could have obscured potential differences between both treatment regimens.
Implications of all available evidence
Hypofractionated treatment with 19 fractions of 3·4 Gy cannot be regarded as the standard of care for patients with intermediate-risk and high-risk prostate cancer. Hypofractionation could be offered to selected patients with few genitourinary and gastrointestinal baseline complaints based on our previously published acute and late toxicity results. Prolonged follow-up of the HYPRO trial results and those of other large randomised trials is needed to define further the role of hypofractionation for prostate cancer in clinical practice.