David Joseph1, James W Denham2, Allison Steigler3, David S Lamb4, Nigel A Spry5, John Stanley6, Tom Shannon7, Gillian Duchesne8, Chris Atkinson9, John H L Matthews10, Sandra Turner11, Lizbeth Kenny12, David Christie13, Keen-Hun Tai8, Nirdosh Kumar Gogna14, Rachel Kearvell15, Judy Murray4, Martin A Ebert16, Annette Haworth17, Brett Delahunt4, Christopher Oldmeadow18, John Attia18. 1. Department of Medicine and Surgery, University of Western Australia, Western Australia, Australia; GenesisCare, Joondalup, Western Australia, Australia; 5D Clinics, Claremont, Western Australia, Australia. 2. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia. Electronic address: Jim.Denham@newcastle.edu.au. 3. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia. 4. Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand. 5. GenesisCare, Joondalup, Western Australia, Australia. 6. Hollywood Specialist Centre, Nedlands, Western Australia, Australia. 7. The Prostate Clinic, Nedlands, Western Australia, Australia. 8. Peter MacCallum Cancer Centre and University of Melbourne, Victoria, Australia. 9. St Georges Cancer Care Centre, Christchurch, New Zealand. 10. Cancer and Blood Services, Auckland District Health Board, Auckland, New Zealand. 11. Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia. 12. Royal Brisbane and Women's Hospital, Brisbane, Australia; School of Medicine, University of Queensland, Queensland, Australia. 13. Genesiscare, Tugun, Queensland, Australia. 14. Mater Radiation Oncology Centre, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 15. GenesisCare, St Andrew's Hospital, Adelaide, South Australia, Australia. 16. 5D Clinics, Claremont, Western Australia, Australia; Department of Physics, University of Western Australia, Crawley, Western Australia, Australia. 17. School of Physics, University of Sydney, Sydney, New South Wales. 18. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Abstract
PURPOSE: To clarify the relative effects of duration of androgen suppression (AS) and radiation dose escalation (RDE) on distant progression (DP) in men with locally advanced prostate cancer. METHODS AND MATERIALS: Participants with locally advanced prostate cancer in the TROG 03.04 RADAR trial were randomized to 6 or 18 months AS ± 18 months zoledronic acid (Z). The trial incorporated a RDE program by stratification at randomization and dosing options were 66, 70, or 74 Gy external beam radiation therapy (EBRT), or 46 Gy EBRT plus high-dose-rate brachytherapy boost (HDRB). The primary endpoint for this study was distant progression (DP). Secondary endpoints included local progression, bone progression, prostate cancer-specific mortality and all-cause mortality. Effect estimates for AS duration and RDE were derived using Fine and Gray competing risk models adjusting for use of Z, age, tumor stage, Gleason grade group, prostate-specific antigen, and treatment center. Cumulative incidence at 10 years was estimated for each RDE group. RESULTS:A total of 1051 out of 1071 randomized subjects were eligible for inclusion in this analysis. Compared with 6 months AS, 18 months AS significantly reduced DP independently of radiation dose (subhazard ratio 0.70; 95% confidence interval [CI], 0.56-0.87; P = .002). No statistically significant interaction between effect of AS duration and RT dose was observed (Wald test P = .76). In subgroup analyses, DP was significantly reduced by the longer duration of AS in the 70 Gy and HDRB groups but not in the 66 Gy and 74 Gy. Compared with 70 Gy, HDRB significantly reduced DP (subhazard ratio 0.68 [95% CI, 0.57-0.80]; P < .0001) independently of AS duration. At 10 years, adjusted cumulative incidences were 26.1% (95% CI, 18.9%-33.2%), 26.7% (22.9%-30.6%), 24.9% (20.0%-29.8%) and 19.7% (15.5%-23.8%) for DPs in the respective radiation dose groups. CONCLUSIONS: Compared with 6 months AS, 18 months AS reduced DP independently of radiation dose. Men treated with HDRB gained a significant benefit from a longer duration of AS. Evidence of improved oncologic outcomes for HDRB compared with dose-escalated EBRT needs to be confirmed in a randomized trial.
RCT Entities:
PURPOSE: To clarify the relative effects of duration of androgen suppression (AS) and radiation dose escalation (RDE) on distant progression (DP) in men with locally advanced prostate cancer. METHODS AND MATERIALS: Participants with locally advanced prostate cancer in the TROG 03.04 RADAR trial were randomized to 6 or 18 months AS ± 18 months zoledronic acid (Z). The trial incorporated a RDE program by stratification at randomization and dosing options were 66, 70, or 74 Gy external beam radiation therapy (EBRT), or 46 Gy EBRT plus high-dose-rate brachytherapy boost (HDRB). The primary endpoint for this study was distant progression (DP). Secondary endpoints included local progression, bone progression, prostate cancer-specific mortality and all-cause mortality. Effect estimates for AS duration and RDE were derived using Fine and Gray competing risk models adjusting for use of Z, age, tumor stage, Gleason grade group, prostate-specific antigen, and treatment center. Cumulative incidence at 10 years was estimated for each RDE group. RESULTS: A total of 1051 out of 1071 randomized subjects were eligible for inclusion in this analysis. Compared with 6 months AS, 18 months AS significantly reduced DP independently of radiation dose (subhazard ratio 0.70; 95% confidence interval [CI], 0.56-0.87; P = .002). No statistically significant interaction between effect of AS duration and RT dose was observed (Wald test P = .76). In subgroup analyses, DP was significantly reduced by the longer duration of AS in the 70 Gy and HDRB groups but not in the 66 Gy and 74 Gy. Compared with 70 Gy, HDRB significantly reduced DP (subhazard ratio 0.68 [95% CI, 0.57-0.80]; P < .0001) independently of AS duration. At 10 years, adjusted cumulative incidences were 26.1% (95% CI, 18.9%-33.2%), 26.7% (22.9%-30.6%), 24.9% (20.0%-29.8%) and 19.7% (15.5%-23.8%) for DPs in the respective radiation dose groups. CONCLUSIONS: Compared with 6 months AS, 18 months AS reduced DP independently of radiation dose. Men treated with HDRB gained a significant benefit from a longer duration of AS. Evidence of improved oncologic outcomes for HDRB compared with dose-escalated EBRT needs to be confirmed in a randomized trial.
Authors: Neal Andruska; Temitope Agabalogun; Benjamin W Fischer-Valuck; Randall J Brenneman; Yi Huang; Hiram A Gay; Jeff M Michalski; Ruben Carmona; Brian C Baumann Journal: Brachytherapy Date: 2022-05-28 Impact factor: 2.441
Authors: I-Chow Hsu; Joseph P Rodgers; Katsuto Shinohara; James Purdy; Jeff Michalski; Mack Roach; Eric Vigneault; Robert A Ivker; Rodger M Pryzant; Michael Kuettel; Daniel Taussky; Gary S Gustafson; Adam Raben; Howard M Sandler Journal: Int J Radiat Oncol Biol Phys Date: 2020-11-10 Impact factor: 8.013
Authors: Amar U Kishan; R Jeffrey Karnes; Tahmineh Romero; Jessica K Wong; Giovanni Motterle; Jeffrey J Tosoian; Bruce J Trock; Eric A Klein; Bradley J Stish; Robert T Dess; Daniel E Spratt; Avinash Pilar; Chandana Reddy; Rebecca Levin-Epstein; Trude B Wedde; Wolfgang A Lilleby; Ryan Fiano; Gregory S Merrick; Richard G Stock; D Jeffrey Demanes; Brian J Moran; Michelle Braccioforte; Hartwig Huland; Phuoc T Tran; Santiago Martin; Rafael Martínez-Monge; Daniel J Krauss; Eyad I Abu-Isa; Ridwan Alam; Zeyad Schwen; Albert J Chang; Thomas M Pisansky; Richard Choo; Daniel Y Song; Stephen Greco; Curtiland Deville; Todd McNutt; Theodore L DeWeese; Ashley E Ross; Jay P Ciezki; Paul C Boutros; Nicholas G Nickols; Prashant Bhat; David Shabsovich; Jesus E Juarez; Natalie Chong; Patrick A Kupelian; Anthony V D'Amico; Matthew B Rettig; Alejandro Berlin; Jonathan D Tward; Brian J Davis; Robert E Reiter; Michael L Steinberg; David Elashoff; Eric M Horwitz; Rahul D Tendulkar; Derya Tilki Journal: JAMA Netw Open Date: 2021-07-01
Authors: Amit Roy; Randall J Brenneman; Jacob Hogan; Justin M Barnes; Yi Huang; Robert Morris; Sreekrishna Goddu; Michael Altman; Jose Garcia-Ramirez; Harold Li; Jacqueline E Zoberi; Arnold Bullock; Eric Kim; Zachary Smith; Robert Figenshau; Gerald L Andriole; Brian C Baumann; Jeff M Michalski; Hiram A Gay Journal: Clin Transl Radiat Oncol Date: 2021-05-13