title: Association of prostate-specific antigen doubling time and cancer in men undergoing repeat prostate biopsy.
abstract: OBJECTIVE
  To analyze the association between prostate-specific antigen doubling time with prostate cancer risk and grade among men with prostate-specific antigen levels ≥4.0 ng/mL undergoing repeat prostate biopsy.
  
  
  METHODS
  A total of 286 patients with prostate-specific antigen ≥4 ng/mL and available prostate-specific antigen doubling time data, who underwent repeat prostate biopsy from 1996-2009, were included in this analysis. Prostate-specific antigen doubling time was divided into three groups: >9 years, 3-9 years and <3 years. Multivariate analyses of prostate-specific antigen doubling time with cancer risk and grade (≤3 + 4 vs ≥4 + 3) were carried out using logistic regression adjusting for prebiopsy prostate-specific antigen, race, age, digital rectal examination, year of biopsy and number of prior negative biopsies.
  
  
  RESULTS
  The median prostate-specific antigen doubling time before biopsy was 4.5 years (interquartile range = 2.5-10). Shorter prostate-specific antigen doubling time was associated with higher prostate-specific antigen (P < 0.001), but it was unrelated to age, digital rectal examination or race. Shorter prostate-specific antigen doubling time as a continuous variable was associated with greater prostate cancer risk in both uni- (hazard ratio = 0.99, 95% confidence interval = 0.98-0.99, P = 0.001) and multivariate analysis (hazard ratio = 0.99, 95% confidence interval = 0.98-0.99, P = 0.004). The prevalence of cancer among prostate-specific antigen doubling time groups (>9, 3-9, <3 years) was 17%, 37% and 40%, respectively. Shorter prostate-specific antigen doubling time groups were associated with higher cancer risk (P = 0.001). Stratified by grade, short prostate-specific antigen doubling time as a continuous variable significantly predicted both low- (P = 0.010) and high-grade disease (P = 0.049). The inclusion of prostate-specific antigen doubling time groups in a multivariate model to predict biopsy positivity increased its accuracy from 0.69 to 0.74.
  
  
  CONCLUSIONS
  Prostate-specific antigen doubling time seems to provide further cancer risk assessment in men undergoing repeat biopsy for prostate-specific antigen ≥4.0 ng/mL. If validated in future studies, the present findings support the use of prostate-specific antigen doubling time in the risk stratification of this patient population.
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Duke Prostate Center, Duke University School of Medicine, Durham, North Carolina 27710, USA. daniel.moreira@duke.edu
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Moreira
authors.forename: Leah
authors.initials: L
authors.lastname: Gerber
authors.forename: Jean-Alfred
authors.initials: JA
authors.lastname: Thomas
authors.forename: Lionel L
authors.initials: LL
authors.lastname: Bañez
authors.forename: Madeline G
authors.initials: MG
authors.lastname: McKeever
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000368:Aged; D001706:Biopsy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology*
chemical_list: D017430:Prostate-Specific Antigen