Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer: The Triumph of Radiobiology

Background: Radiotherapy represents one of the main therapeutic modalities for localized prostate cancer. In the last two decades, emerging data regarding the radiobiology of prostate cancer suggests a very low α/β value, which has led the scientific community to evaluate the potential advantage of hypofractionation. Objective: The aim of this manuscript is to present the rationale of prostate radiobiology and the medical evidence of moderate hypofractionation for prostate cancer. Methods: Existing literature was reviewed, including data from prospective clinical trials dealing with the efficacy and toxicity of hypofractionated radiotherapy. Fifteen prospective phase II studies, nine randomized phase III studies and ten meta-analyses were selected. For every study included, the equivalent dose was calculated for both biochemical control and late toxicity. Results: The efficacy of hypofractionated radiotherapy, compared to conventional radiotherapy, regarding biochemical control, was evaluated in five superiority and four non-inferiority randomized phase III studies. The majority of participants in these studies were patients with low- and intermediate- risk prostate cancer. Even though the superiority criterion of the hypofractionation was not met in all studies, the noninferiority criterion was met. Prospective phase II studies of hypofractionation reported a low rate of acute and late toxicity. In randomized phase III studies, acute and late toxicity grade 3 and higher for the bowel and bladder was comparable between hypofractionated and conventional radiotherapy. The included meta-analyses showed no difference in efficacy and toxicity. Conclusion: Moderate hypofractionation is feasible and safe, and may be considered as an alternative option in low- and intermediate-risk prostate cancer patients.