title: Free prostate-specific antigen improves prostate cancer detection in a high-risk population of men with a normal total PSA and digitalrectal examination.
abstract: OBJECTIVE
  Uncertainty exists regarding optimal prostate cancer screening parameters for high-risk populations. The purpose of this study is to report the use of percent free prostate-specific antigen (PSA) as an indication for biopsy in men at increased risk for developing prostate cancer who have a normal digital rectal examination (DRE) and total PSA level between 2 and 4 ng/mL.
  
  
  METHODS
  African-American men and men with at least one first-degree relative with prostate cancer are eligible for enrollment into the Prostate Cancer Risk Assessment Program (PRAP) at our institution. Between October 1996 and April 2002, 310 asymptomatic high-risk men with no history of prostate cancer, benign prostatic hyperplasia (BPH), or prostatic intraepithelial neoplasia (PIN) were screened in the PRAP with DRE and total PSA. Percent free PSA was obtained in men with a total PSA between 2 and 10 ng/mL. Men with a normal DRE and total PSA between 2 and 4 ng/mL were advised to undergo transrectal ultrasound-guided (TRUS) biopsies of the prostate if the percent free PSA was less than 27%. Other indications for biopsy included an abnormal DRE or a total PSA greater than 4 ng/mL. The primary endpoint evaluated was prostate cancer detection in high-risk men with a benign prostate examination, a normal total PSA between 2 and 4 ng/mL, and percent free PSA less than 27%.
  
  
  RESULTS
  Of the 310 men, 174 (56%) were African American and 202 (65%) had at least one first-degree relative with prostate cancer. Sixty-two of the 310 men were referred for prostate biopsy, and 40 of 62 had biopsy performed. Twenty-one of 40 men were diagnosed with prostate cancer for a cancer detection rate of 53% in all men undergoing biopsy and an overall cancer detection rate of 6.8% in this high-risk population. Thirty-seven high-risk men (median age 54 years) with a total PSA level between 2 and 4 ng/mL (median 2.7 ng/mL) and a normal DRE were found to have a percent free PSA level of less than 27% (median 16%, range 8% to 25%). Twenty-three of these 37 men (62%) proceeded with the recommended prostate biopsy. Prostatic adenocarcinoma was diagnosed in 12 of 23 men for a cancer detection rate of 52% in men undergoing biopsy and 32% in all men with a normal DRE, a total PSA between 2 and 4 ng/mL, and a percent free PSA less than 27%. All positive biopsies demonstrated clinically significant Gleason score 6 or 7 disease. In all men electing radical prostatectomy, bilateral organ-confined disease (pT2bN0M0) was confirmed.
  
  
  CONCLUSIONS
  In this unique population of men at high risk for prostate cancer, a percent free PSA of less than 27% was found to be useful for detecting early-stage but clinically significant cancers in men with a total PSA value between 2 and 4 ng/mL and normal DRE findings.
authors.affiliation: Department of Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.forename: Wayne H
authors.initials: WH
authors.lastname: Pinover
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Alicia
authors.initials: A
authors.lastname: Parlanti
authors.forename: Susan
authors.initials: S
authors.lastname: Mazzoni
authors.forename: Susan
authors.initials: S
authors.lastname: Raysor
authors.forename: Ila
authors.initials: I
authors.lastname: Mirchandani
authors.forename: Richard E
authors.initials: RE
authors.lastname: Greenberg
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Hanks
authors.forename: Deborah
authors.initials: D
authors.lastname: Watkins-Bruner
mesh_terms: D001707:Biopsy, Needle; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D010173:Palpation; D011467:Prostate / Q000000981:diagnostic imaging / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014463:Ultrasonography
chemical_list: D017430:Prostate-Specific Antigen