title: A multicenter study of [-2]pro-prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate specific antigen range.
abstract: OBJECTIVE
  Prostate specific antigen and free prostate specific antigen have limited specificity to detect clinically significant, curable prostate cancer, leading to unnecessary biopsy, and detection and treatment of some indolent tumors. Specificity to detect clinically significant prostate cancer may be improved by [-2]pro-prostate specific antigen. We evaluated [-2]pro-prostate specific antigen, free prostate specific antigen and prostate specific antigen using the formula, ([-2]pro-prostate specific antigen/free prostate specific antigen × prostate specific antigen(1/2)) to enhance specificity to detect overall and high grade prostate cancer.
  
  
  METHODS
  We enrolled 892 men with no history of prostate cancer, normal rectal examination, prostate specific antigen 2 to 10 ng/ml and 6-core or greater prostate biopsy in a prospective multi-institutional trial. We examined the relationship of serum prostate specific antigen, free-to-total prostate specific antigen and the prostate health index with biopsy results. Primary end points were specificity and AUC using the prostate health index to detect overall and Gleason 7 or greater prostate cancer on biopsy compared with those of free-to-total prostate specific antigen.
  
  
  RESULTS
  In the 2 to 10 ng/ml prostate specific antigen range at 80% to 95% sensitivity the specificity and AUC (0.703) of the prostate health index exceeded those of prostate specific antigen and free-to-total prostate specific antigen. An increasing prostate health index was associated with a 4.7-fold increased risk of prostate cancer and a 1.61-fold increased risk of Gleason score greater than or equal to 4 + 3 = 7 disease on biopsy. The AUC of the index exceeded that of free-to-total prostate specific antigen (0.724 vs 0.670) to discriminate prostate cancer with Gleason 4 or greater + 3 from lower grade disease or negative biopsy. Prostate health index results were not associated with age and prostate volume.
  
  
  CONCLUSIONS
  The prostate health index may be useful in prostate cancer screening to decrease unnecessary biopsy in men 50 years old or older with prostate specific antigen 2 to 10 ng/ml and negative digital rectal examination with minimal loss in sensitivity.
authors.affiliation: Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. wcatalona@nmff.org
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sanda
authors.forename: John T
authors.initials: JT
authors.lastname: Wei
authors.forename: George G
authors.initials: GG
authors.lastname: Klee
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Slawin
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Marks
authors.forename: Stacy
authors.initials: S
authors.lastname: Loeb
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Broyles
authors.forename: Sanghyuk S
authors.initials: SS
authors.lastname: Shin
authors.forename: Amabelle B
authors.initials: AB
authors.lastname: Cruz
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Chan
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Sokoll
authors.forename: William L
authors.initials: WL
authors.lastname: Roberts
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Isaac A
authors.initials: IA
authors.lastname: Mizrahi
mesh_terms: D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012044:Regression Analysis; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen