• Bridget F Koontz, Alberto Bossi, Cesare Cozzarini, Thomas Wiegel, and Anthony D'Amico.
• Department of Radiation Oncology, Duke Cancer Institute, Durham, NC, USA. Electronic address: bridget.koontz@duke.edu.
• Eur. Urol. 2015 Oct 1; 68 (4): 683-91.

ContextTechnological advances in radiation therapy delivery have permitted the use of high-dose-per-fraction radiation therapy (RT) for early-stage prostate cancer (PCa). Level 1 evidence supporting the safety and efficacy of hypofractionated RT is evolving as this modality becomes more widely utilized and refined.ObjectiveTo perform a systematic review of the current evidence on the safety and efficacy of hypofractionated RT for early-stage PCa and to provide in-context recommendations for current application of this technology.Evidence AcquisitionEmbase, PubMed, and Scopus electronic databases were queried for English-language articles from January 1990 through June 2014. Prospective studies with a minimum of 50 patients were included. Separate consideration was made for studies involving moderate hypofractionation (doses of 2.5-4Gy per fraction) and extreme hypofractionation (5-10Gy in 4-7 fractions).Evidence SynthesisSix relatively small superiority designed randomized trials of standard fractionation versus moderate hypofractionation in predominantly low- and intermediate-risk PCa have been published with follow-up ranging from 4 to 8 yr, noting similar biochemical control (5-yr freedom from biochemical failure in modern studies is >80% for low-risk and intermediate-risk patients) and late grade ≥2 genitourinary and gastrointestinal toxicities (between 2% and 20%). Noninferiority studies are pending. In prospective phase 2 studies, extreme hypofractionation has promising 2- to 5-yr biochemical control rates of >90% for low-risk patients. Results from a randomized trial are expected in 2015.ConclusionsModerate hypofractionation has 5-yr data to date establishing safety compared with standard fractionation, but 10-yr outcomes and longer follow-up are needed to establish noninferiority for clinical effectiveness. Extreme hypofractionation is promising but as yet requires reporting of randomized data prior to application outside of a clinical protocol.Patient SummaryHypofractionation for prostate cancer delivers relatively high doses of radiation per treatment. Prospective studies support the safety of moderate hypofractionation, while extreme fractionation may have greater toxicity. Both show promising cancer control but long-term results of noninferiority studies of both methods are required before use in routine treatment outside of clinical protocols.Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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