title: Risk factors for prostate cancer detection after a negative biopsy: a novel multivariable longitudinal approach.
abstract: OBJECTIVE
  To introduce a novel approach for the time-dependent quantification of risk factors for prostate cancer (PCa) detection after an initial negative biopsy.
  
  
  METHODS
  Data for 1,871 men with initial negative biopsies and at least one follow-up biopsy were available. Piecewise exponential regression models were developed to quantify hazard ratios (HRs) and define cumulative incidence curves for PCa detection for subgroups with specific patterns of risk factors over time. Factors evaluated included age, race, serum prostate-specific antigen (PSA) concentration, PSA slope, digital rectal examination, dysplastic glands or prostatitis on biopsy, ultrasound gland volume, urinary symptoms, and number of negative biopsies.
  
  
  RESULTS
  Four hundred sixty-five men had PCa detected, after a mean follow-up time of 2.8 years. All of the factors were independent predictors of PCa detection except for PSA slope, as a result of its correlation with time-dependent PSA level, and race. PSA (HR = 3.90 for > 10 v 2.5 to 3.9 ng/mL), high-grade prostatic intraepithelial neoplasia/atypical glands (HR = 2.97), gland volume (HR = 0.39 for > 50 v < 25 mL), and number of repeat biopsies (HR = 0.36 for two v zero repeat biopsies) were the strongest predictors. Men with high-risk versus low-risk event histories had a 20-fold difference in PCa detection over 5 years.
  
  
  CONCLUSIONS
  Piecewise exponential models provide an approach to longitudinal analysis of PCa risk that allows clinicians to see the interplay of risk factors as they unfold over time for individual patients. With these models, it is possible to identify distinct subpopulations with dramatically different needs for monitoring and repeat biopsy.
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA. pgann@uic.edu
authors.forename: Peter H
authors.initials: PH
authors.lastname: Gann
authors.forename: Angela
authors.initials: A
authors.lastname: Fought
authors.forename: Ryan
authors.initials: R
authors.lastname: Deaton
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: Edward
authors.initials: E
authors.lastname: Vonesh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D012307:Risk Factors; D013997:Time Factors