title: Impact of prostate-specific antigen on a baseline prostate cancer risk assessment including genetic risk.
abstract: OBJECTIVE
  To determine to what extent prostate cancer (PCa) risk prediction is improved by adding prostate-specific antigen (PSA) to a baseline model including genetic risk.
  
  
  METHODS
  Peripheral blood deoxyribonucleic acid was obtained from Caucasian men undergoing prostate biopsy at the University of Toronto (September 1, 2008 to January 31, 2010). Thirty-three PCa risk-associated single nucleotide polymorphisms were genotyped to generate the prostate cancer genetic score 33 (PGS-33). Primary outcome is PCa on study prostate biopsy. Logistic regression, area under the receiver-operating characteristic curves (AUC), and net reclassification improvement were used to compare models.
  
  
  RESULTS
  Among 670 patients, 323 (48.2%) were diagnosed with PCa. The PGS-33 was highly associated with biopsy-detectable PCa (odds ratio, 1.66; P = 5.86E-05; AUC, 0.59) compared with PSA (odds ratio, 1.33; P = .01; AUC, 0.55). PSA did not improve risk prediction when added to a baseline model (age, family history, digital rectal examination, and PGS-33) for overall risk (AUC, 0.66 vs 0.66; P = .86) or Gleason score ≥7 PCa (AUC, 0.71 vs 0.73; P = .15). Net reclassification improvement analyses demonstrated no appropriate reclassifications with the addition of PSA to the baseline model for overall PCa but did show some benefit for reclassification of men thought to be at higher baseline risk in the high-grade PCa analysis.
  
  
  CONCLUSIONS
  In a baseline model of PCa risk including the PGS-33, PSA does not add to risk prediction for overall PCa for men presenting for "for-cause" biopsy. These findings suggest that PSA screening may be minimized in men at low baseline risk.
authors.affiliation: Department of Urology, Moores Cancer Center, University of California San Diego, San Diego, CA. Electronic address: kkader@ucsd.edu.
authors.forename: A Karim
authors.initials: AK
authors.lastname: Kader
authors.affiliation: Department of Urology, Moores Cancer Center, University of California San Diego, San Diego, CA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Liss
authors.affiliation: Division of Urology, Department of Surgery, University Health Network, Toronto, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Trottier
authors.affiliation: Departments of Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Departments of Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Departments of Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: Division of Urology, Department of Surgery, University Health Network, Toronto, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Chadwick
authors.affiliation: Canadian Partnership Against Cancer, Toronto, Canada.
authors.forename: Gina
authors.initials: G
authors.lastname: Lockwood
authors.affiliation: Departments of Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Division of Urology, Department of Surgery, University Health Network, Toronto, Canada.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Fleshner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D017430:Prostate-Specific Antigen