ESOU 2019: Treatment of Gleason 3+4 in a Multidisciplinary Scenario: Hypofractionation Radiation Therapy

Prague, Czech Republic (UroToday.com) As part of the multidisciplinary prostate cancer session at ESOU 2019 discussing treatment options for men with Gleason 3+4 disease, Dr. Alberto Bossi presented his thoughts on hypofractionated radiation therapy.

Dr. Bossi started with highlighting for the urologists in the room the dose and fractionation schedule for conventional, moderate and extreme treatment plans:
ESOU 2019 UroToday Treatment of Gleason 34 in a Multidisciplinary Scenario Hypofractionation Radiation Therapy

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
Dr. Bossi then took the opportunity to review the non-inferiority trials in detail:

  • 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. 
Dr. Bossi’s summary of these three non-inferiority trials was (i) all three are consistent with non-inferiority, for low and intermediate risk patients, (ii) there is very little difference in toxicity between hypofractionated and conventional fractionation cohorts, and (iii) dose beyond 60/62 Gy should be used within clinical trials.


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

Further Related Content:
Treatment of Gleason 3+4 in a Multidisciplinary Scenario: Active Surveillance
Treatment of Gleason 3+4 in a Multidisciplinary Scenario: Focal Therapy

Treatment of Gleason 3+4 in a Multidisciplinary Scenario: Surgery  


References:
  1. 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.
  2. 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.
  3. 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.


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