title: Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial.
abstract: BACKGROUND
  Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer.
  
  
  METHODS
  818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat.
  
  
  RESULTS
  802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3 months' treatment had significantly improved local failure (hazard ratio [HR] 0.56 [95% CI 0.39-0.79], p=0.001), biochemical failure-free survival (0.70 [0.56-0.88], p=0.002), disease-free survival (0.65 [0.52-0.80], p=0.0001), and freedom from salvage treatment (0.73 [0.56-0.96], p=0.025). 6 months' androgen deprivation significantly improved local failure (0.42 [0.28-0.62], p<0.0001), biochemical failure-free survival (0.58 [0.46-0.74], p<0.0001), disease-free survival (0.56 [0.45-0.69], p<0.0001), freedom from salvage treatment (0.53 [0.40-0.71], p<0.0001), distant failure (0.67 [0.45-0.99], p=0.046) and prostate-cancer-specific survival (0.56 [0.32-0.98], p=0.04) compared with no androgen deprivation.
  
  
  CONCLUSIONS
  6 months' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit.
authors.affiliation: Newcastle Mater Hospital, Newcastle, New South Wales, Australia. Jim.Denham@newcastle.edu.au
authors.forename: James W
authors.initials: JW
authors.lastname: Denham
authors.forename: Allison
authors.initials: A
authors.lastname: Steigler
authors.forename: David S
authors.initials: DS
authors.lastname: Lamb
authors.forename: David
authors.initials: D
authors.lastname: Joseph
authors.forename: Hedy
authors.initials: H
authors.lastname: Mameghan
authors.forename: Sandra
authors.initials: S
authors.lastname: Turner
authors.forename: John
authors.initials: J
authors.lastname: Matthews
authors.forename: Ian
authors.initials: I
authors.lastname: Franklin
authors.forename: Chris
authors.initials: C
authors.lastname: Atkinson
authors.forename: John
authors.initials: J
authors.lastname: North
authors.forename: Michael
authors.initials: M
authors.lastname: Poulsen
authors.forename: David
authors.initials: D
authors.lastname: Christie
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Spry
authors.forename: Keen-Hun
authors.initials: KH
authors.lastname: Tai
authors.forename: Chris
authors.initials: C
authors.lastname: Wynne
authors.forename: Gillian
authors.initials: G
authors.lastname: Duchesne
authors.forename: Olga
authors.initials: O
authors.lastname: Kovacev
authors.forename: Catherine
authors.initials: C
authors.lastname: D'Este
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005485:Flutamide / Q000627:therapeutic use*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*
chemical_list: D000726:Androgen Antagonists; D017273:Goserelin; D005485:Flutamide