title: Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial.
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.
  
  
  CONCLUSIONS
  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.affiliation: School of Medicine and Public Health, University of Newcastle, Australia. Electronic address: Jim.Denham@newcastle.edu.au.
authors.forename: James W
authors.initials: JW
authors.lastname: Denham
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Australia.
authors.forename: Allison
authors.initials: A
authors.lastname: Steigler
authors.affiliation: Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Joseph
authors.affiliation: Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand.
authors.forename: David S
authors.initials: DS
authors.lastname: Lamb
authors.affiliation: Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Spry
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Gillian
authors.initials: G
authors.lastname: Duchesne
authors.affiliation: St Georges Cancer Care Centre, Christchurch, New Zealand.
authors.forename: Chris
authors.initials: C
authors.lastname: Atkinson
authors.affiliation: Auckland Hospital, New Zealand.
authors.forename: John
authors.initials: J
authors.lastname: Matthews
authors.affiliation: Westmead Hospital, Sydney, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Turner
authors.affiliation: Royal Brisbane and Women's Hospital, Australia.
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Kenny
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Keen-Hun
authors.initials: KH
authors.lastname: Tai
authors.affiliation: Mater Radiation Oncology Centre, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Nirdosh Kumar
authors.initials: NK
authors.lastname: Gogna
authors.affiliation: Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Suki
authors.initials: S
authors.lastname: Gill
authors.affiliation: Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Hendrick
authors.initials: H
authors.lastname: Tan
authors.affiliation: Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kearvell
authors.affiliation: Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand.
authors.forename: Judy
authors.initials: J
authors.lastname: Murray
authors.affiliation: Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Ebert
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Annette
authors.initials: A
authors.lastname: Haworth
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Angel
authors.initials: A
authors.lastname: Kennedy
authors.affiliation: Wellington School of Medicine and Health Sciences, University of Otago, New Zealand.
authors.forename: Brett
authors.initials: B
authors.lastname: Delahunt
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Australia; Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Oldmeadow
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Australia; Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Holliday
authors.affiliation: School of Medicine and Public Health, University of Newcastle, Australia; Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Attia
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001918:Brachytherapy; D059248:Chemoradiotherapy; D004164:Diphosphonates / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D016896:Treatment Outcome; D014525:Urethral Stricture / Q000209:etiology; D000077211:Zoledronic Acid
chemical_list: D000726:Androgen Antagonists; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Androgen suppression; Dose escalation; High dose rate brachytherapy boost; Prostate cancer