title: Early versus delayed hormonal therapy for prostate specific antigen only recurrence of prostate cancer after radical prostatectomy.
abstract: OBJECTIVE
  Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen (PSA) only recurrence (PSAR), however, there is virtually no published literature comparing HT to observation in the clinical setting. The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational database to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach.
  
  
  METHODS
  Of 5382 men in the database who underwent primary radical prostatectomy (RP), 4967 patients were treated in the PSA-era between 1988 and December 2002. Of those patients 1352 men who had PSAR (PSA after surgery greater than 0.2 ng/ml) and had postoperative followup greater than 6 months were used as the study cohort. These patients were further divided into an early HT group in which patients (355) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients (997) who received no HT before clinical metastasis or by current followup. The primary end point was the development of clinical metastases. Of the 1352 patients with PSAR clinical metastases developed in 103 (7.6%). Patients were also stratified by surgical Gleason sum, PSA doubling time and timing of recurrence. Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome.
  
  
  RESULTS
  Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less (Hazards ratio = 2.12, p = 0.01). However, in the overall cohort early HT did not impact clinical metastases. Race, age at RP and PSA at diagnosis had no effect on metastasis-free survival (p >0.05).
  
  
  CONCLUSIONS
  The retrospective observational multicenter database analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup. Further study with longer followup and randomized trials are needed to address this important issue.
authors.affiliation: Department of Surgery, Uniformed Services University of the Health Sciences, National Naval Medical Center, Bethesda 20852, USA. jmoul@cpdr.org
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wu
authors.forename: Leon
authors.initials: L
authors.lastname: Sun
authors.forename: David G
authors.initials: DG
authors.lastname: McLeod
authors.forename: Christopher
authors.initials: C
authors.lastname: Amling
authors.forename: Timothy
authors.initials: T
authors.lastname: Donahue
authors.forename: Leo
authors.initials: L
authors.lastname: Kusuda
authors.forename: Wade
authors.initials: W
authors.lastname: Sexton
authors.forename: Keith
authors.initials: K
authors.lastname: O'Reilly
authors.forename: Javier
authors.initials: J
authors.lastname: Hernandez
authors.forename: Andrew
authors.initials: A
authors.lastname: Chung
authors.forename: Douglas
authors.initials: D
authors.lastname: Soderdahl
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D012189:Retrospective Studies; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen