Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer

Abstract

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.

Faculty of Radiation Oncology 2018 workforce census

“…Hypofractionation has been widely adopted with highest utilisation in breast cancer, but recent randomised trials on both prostate cancer and glioblastoma multiforme demonstrating noninferiority should see these areas rise …”

Impact of interfractional motion on hypofractionated pencil beam scanning proton therapy and VMAT delivery for prostate cancer

“…Although radiotherapy of prostate is currently practiced using standard fractionation regimens (eg, 44 fx at 1.8 Gy/fx over ~9 weeks), hypofractionation is gaining more clinical attention and momentum. Several clinical trials have found hypofractionated radiotherapy to be well‐tolerated by prostate cancer patients with no apparent differences in outcome and toxicities . Moderate hypofractionation protocols (eg, 60 Gy in 20 fx) were demonstrated as non‐inferior to conventional fractionations and were recommended to become the new standard of care for radiotherapy of localized prostate cancer …”

Use of hydrogel spacer for improved rectal dose-sparing in patients undergoing radical radiotherapy for localized prostate cancer: First Canadian experience

“…7 Based on this and other studies, [8][9] mild hypofractionation has become an accepted and increasingly adopted dose schedule at ours and many other institutions. Nonetheless, in approximately 10-25% of cases, strict rectal dose-constraints are not met, generating a concern for increased risk of late toxicities, particularly in the context of higher dose per fraction.…”