James W Denham1, Allison Steigler2, David Joseph3, David S Lamb4, Nigel A Spry3, Gillian Duchesne5, Chris Atkinson6, John Matthews7, Sandra Turner8, Lizbeth Kenny9, Keen-Hun Tai5, Nirdosh Kumar Gogna10, Suki Gill3, Hendrick Tan3, Rachel Kearvell3, Judy Murray4, Martin Ebert3, Annette Haworth5, Angel Kennedy5, Brett Delahunt11, Christopher Oldmeadow12, Elizabeth G Holliday12, John Attia12. 1. School of Medicine and Public Health, University of Newcastle, Australia. Electronic address: Jim.Denham@newcastle.edu.au. 2. School of Medicine and Public Health, University of Newcastle, Australia. 3. Sir Charles Gairdner Hospital, Perth, Australia. 4. Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand. 5. Peter MacCallum Cancer Centre, Melbourne, Australia. 6. St Georges Cancer Care Centre, Christchurch, New Zealand. 7. Auckland Hospital, New Zealand. 8. Westmead Hospital, Sydney, Australia. 9. Royal Brisbane and Women's Hospital, Australia. 10. Mater Radiation Oncology Centre, Princess Alexandra Hospital, Brisbane, Australia. 11. Wellington School of Medicine and Health Sciences, University of Otago, New Zealand. 12. School of Medicine and Public Health, University of Newcastle, Australia; Hunter Medical Research Institute, Newcastle, Australia.
Abstract
BACKGROUND: The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. METHODS: We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS±18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. RESULTS:Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (p<0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively. CONCLUSION: RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration.
RCT Entities:
BACKGROUND: The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. METHODS: We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS±18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. RESULTS: Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (p<0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively. CONCLUSION: RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration.
Authors: Calyn R Moulton; Michael J House; Victoria Lye; Colin I Tang; Michele Krawiec; David J Joseph; James W Denham; Martin A Ebert Journal: Radiat Oncol Date: 2016-10-31 Impact factor: 3.481
Authors: Calyn R Moulton; Michael J House; Victoria Lye; Colin I Tang; Michele Krawiec; David J Joseph; James W Denham; Martin A Ebert Journal: Radiat Oncol Date: 2015-12-14 Impact factor: 3.481
Authors: Georgia K B Halkett; Michala Short; Samar Aoun; David Joseph; Sean Bydder; Xingqiong Meng; Nigel Spry Journal: J Contemp Brachytherapy Date: 2017-10-10