title: The change of PSA doubling time and its association with disease progression in patients with biochemically relapsed prostate cancer treated with intermittent androgen deprivation.
abstract: BACKGROUND
  We sought to determine the change of PSA doubling time (PSADT) and its association with disease progression during intermittent androgen deprivation (IAD) therapy for prostate cancer.
  
  
  METHODS
  Data were retrospectively analyzed in 96 patients with biochemically relapsed prostate cancer (BRPC) treated with IAD since 1995. IAD consisted of LHRH-agonists ± antiandrogen given usually at PSA threshold (ng/ml) of 10-20, for 6-9 months. Cycles were repeated until the development of castration resistance. Mixed effects model was used to study PSADT change over cycles. Multivariate cox regression model was used to identify outcome-associated variables.
  
  
  RESULTS
  Patients received a mean of 2.8 treatment cycles over a mean follow-up time of 71 months. Fifty-seven (59%) remain on treatment and 39 (41%) developed PSA refractoriness (n = 8) or positive scans (n = 31). First off treatment interval PSADT (median 2.3 months) was significantly shorter than the baseline (median 7.34) but remained stable in subsequent cycles. Off treatment interval PSADT adjusted for testosterone recovery (median 3.7) was significantly longer than that based on all PSA determinations (median 2). Factors associated with disease progression were pre-treatment PSADT (≥6 vs. <6), first off treatment interval PSADT (≥3 vs. <3), and PSA nadir during the first treatment interval (<0.1 vs. ≥0.1).
  
  
  CONCLUSIONS
  During IAD for BRPC, PSADT becomes shorter, and is associated with testosterone recovery. PSADT before treatment and during the first off treatment interval is associated with disease progression. If prospectively validated these data may guide treatment with IAD and clinical trial design.
authors: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA. dkejzma2@jhmi.edu
authors: Daniel
authors: D
authors: Keizman
authors: Peng
authors: P
authors: Huang
authors: Emmanuel S
authors: ES
authors: Antonarakis
authors: Victoria
authors: V
authors: Sinibaldi
authors: Michael A
authors: MA
authors: Carducci
authors: Samuel
authors: S
authors: Denmeade
authors: Jenny J
authors: JJ
authors: Kim
authors: Janet
authors: J
authors: Walczak
authors: Mario A
authors: MA
authors: Eisenberger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage*; D018450:Disease Progression; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009376:Neoplasms, Hormone-Dependent / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D013739:Testosterone / Q000097:blood; D013997:Time Factors
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D017430:Prostate-Specific Antigen