J Clin Oncol 2017 Jun 15;35(17):1884-1890. Epub 2017 Mar 15.
Charles N. Catton, Peter W.M. Chung, Patrick Cheung, Padraig Warde, and Tim K. Craig, University of Toronto, Toronto; Himu Lukka, Chu-Shu Gu, Theodoros Tsakiridis, Tom B. Corbett, Ian S. Dayes, Jim A. Julian, and Mark N. Levine, McMaster University, Hamilton; Glenn S. Bauman, University of Western Ontario, London, Ontario; Jean-Paul Bahary, University of Montreal, Montreal, Quebec; Shahida Ahmed, University of Manitoba, Winnipeg, Manitoba; Jackson S. Wu, University of Calgary, Calgary; Matthew B. Parliament, University of Alberta, Edmonton, Alberta, Canada; Jarad M. Martin, University of Newcastle, Newcastle, New South Wales; Keen Hun Tai, University of Melbourne, Melbourne, Victoria; Colin Tang, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; and Stéphane Supiot, University of Nantes, Nantes, France.
Purpose Men with localized prostate cancer often are treated with external radiotherapy (RT) over 8 to 9 weeks. Hypofractionated RT is given over a shorter time with larger doses per treatment than standard RT. We hypothesized that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity. Patients and Methods We conducted a multicenter randomized noninferiority trial in intermediate-risk prostate cancer (T1 to 2a, Gleason score ≤ 6, and prostate-specific antigen [PSA] 10.1 to 20 ng/mL; T2b to 2c, Gleason ≤ 6, and PSA ≤ 20 ng/mL; or T1 to 2, Gleason = 7, and PSA ≤ 20 ng/mL). Patients were allocated to conventional RT of 78 Gy in 39 fractions over 8 weeks or to hypofractionated RT of 60 Gy in 20 fractions over 4 weeks. Androgen deprivation was not permitted with therapy. The primary outcome was biochemical-clinical failure (BCF) defined by any of the following: PSA failure (nadir + 2), hormonal intervention, clinical local or distant failure, or death as a result of prostate cancer. The noninferiority margin was 7.5% (hazard ratio, < 1.32). Results Median follow-up was 6.0 years. One hundred nine of 608 patients in the hypofractionated arm versus 117 of 598 in the standard arm experienced BCF. Most of the events were PSA failures. The 5-year BCF disease-free survival was 85% in both arms (hazard ratio [short v standard], 0.96; 90% CI, 0.77 to 1.2). Ten deaths as a result of prostate cancer occurred in the short arm and 12 in the standard arm. No significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity. Conclusion The hypofractionated RT regimen used in this trial was not inferior to conventional RT and was not associated with increased late toxicity. Hypofractionated RT is more convenient for patients and should be considered for intermediate-risk prostate cancer.