title: Paradoxical metastatic progression following 3 months of neo-adjuvant androgen suppression in the TROG 96.01 trial for men with locally advanced prostate cancer.
abstract: OBJECTIVE
  In the TROG 96.01 trial 6 month neo-adjuvant androgen suppression (NAS) and radiotherapy (RT) for locally advanced prostate cancer prevented distant progressions (DPs) when compared to RT alone, but 3 months did not. We ask why?
  
  
  METHODS
  Between 1996 and 2000, 802 men with T2-4 N0 M0 prostate cancers received RT alone (0 month NAS) to 66 Gy, 3 months or 6 months NAS before RT. Interval hazards and cumulative incidences of DP were compared using competing risks methodology.
  
  
  RESULTS
  In the first 4 follow-up years 39, 40 and 26 DPs were diagnosed in subjects treated with 0, 3 and 6 month NAS, respectively. Compared with 0 month, significant reductions in PSA doubling time in subjects with DP occurred following 3 month NAS (p=0.01), but a significant reduction (p=0.01) and a near significant delay in DPs (p=0.06) occurred after 6 month NAS. Subsequently 25, 20 and 11 DPs occurred in the three trial arms. After early secondary therapy for PSA or local progression 34, 19 and 12 DPs were diagnosed after median delays of almost 4 years.
  
  
  CONCLUSIONS
  The data are consistent with the failure of 3 month NAS to prevent the progression of sub-clinical metastatic deposits already present before treatment.
authors.affiliation: School of Medicine and Public Health, The University of Newcastle, 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: Keen-Hun
authors.initials: KH
authors.lastname: Tai
authors.forename: David
authors.initials: D
authors.lastname: Joseph
authors.forename: John
authors.initials: J
authors.lastname: Matthews
authors.forename: Chris
authors.initials: C
authors.lastname: Atkinson
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Spry
authors.forename: Sandra
authors.initials: S
authors.lastname: Turner
authors.forename: John
authors.initials: J
authors.lastname: North
authors.forename: David
authors.initials: D
authors.lastname: Christie
authors.forename: Chris
authors.initials: C
authors.lastname: Wynne
authors.forename: David S
authors.initials: DS
authors.lastname: Lamb
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen