Dr. Bossi started with highlighting for the urologists in the room the dose and fractionation schedule for conventional, moderate and extreme treatment plans:
According to Dr. Bossi, there are two different strategies for hypofractionation for treatment of prostate cancer:
- Hypofractionation as a mean to dose escalate (tested in superiority trials) – based on four RCTs, hypofractionation is not superior to standard fractionation
- Hypofractionation as a mean to improve patient convenience and reduce costs (tested in non-inferiority trials) – based on three RCTS, hypofractionation is not inferior to standard fractionation
- 1) RTOG 0415 was designed to assess whether the efficacy of a hypofractionated radiotherapy treatment schedule is no worse than a conventional radiotherapy schedule in men with low-risk prostate cancer 1. There were 1,092 men included with available follow-up information, including 542 patients assigned to conventional radiotherapy (73.8 Gy in 41 fractions over 8.2 weeks) and 550 men to hypofractionated radiotherapy (70 Gy in 28 fractions over 5.6 weeks). Over a median follow-up of 5.8 years, the DFS HR was 0.85 (95%CI, 0.64-1.14), satisfying the non-inferiority criteria (HR < 1.52; p < .001).
- 2) The PROFIT study was a randomized trial designed to test the hypothesis that hypofractionation versus conventional fractionation is similar in efficacy without increased toxicity for patients treated for primary intermediate-risk prostate cancer2. Patients were allocated to conventional radiotherapy of 78 Gy in 39 fractions over 8 weeks (n=598) or to hypofractionated radiotherapy of 60 Gy in 20 fractions over 4 weeks (n=608). Over a median follow-up of 6.0 years, 109 patients in the hypofractionated arm versus 117 in the standard arm experienced biochemical-clinical failure (BCF). The 5-year BCF disease-free survival was 85% in both arms and no significant differences were detected between arms for grade ≥ 3 late genitourinary and GI toxicity.
- 3) The phase III CHHiP trial was designed to assess the efficacy and side-effects of a randomized trial comparing conventional and hypofractionated radiotherapy among patients with T1b-T3aN0M0 prostate cancer with 5 year follow-up 3. Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7.4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks). The primary endpoint for this non-inferiority trial was a biochemical or clinical failure. Among 3,216 patients enrolled, over a median follow-up of 62.4 months, the proportion of patients who were biochemical or clinical failure free at 5 years was 88.3% in the 74 Gy group, 90.6% in the 60 Gy group, and 85.9% in the 57 Gy group. Notably, 60 Gy was non-inferior to 74 Gy (HR 0.84, 90%CI 0.68-1.03) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1.20 90%CI 0.99-1.46). Furthermore, long-term side-effects were similar in the hypofractionated groups and the conventional group.
Presented by: Alberto Bossi, Head of the Urology and Prostate Brachytherapy Unit at the Gustave Roussy Cancer Institute, Villejuif, France
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic
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- Lee WR, Dignam JJ, Amin MB, et al. Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer. J Clin Oncol 2016 Jul 10;34(20);2325-2332.
- Catton CN, Lukka H, Gu CS, et al. Randomized Trial of a Hypofractionated Radiation Regimen for the Treatment of Localized Prostate Cancer. J Clin Oncol 2017 Jun 10;35(17):1884-1890.
- Dearnaley D, Syndikus I, Mossop H, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 2016 Aug;17(8):1047-1060.