title: Derivation and application of upper limits for prostate specific antigen in men aged 50-74 years with no clinical evidence of prostatic carcinoma.
abstract: OBJECTIVE
  To derive age-specific upper limits for prostate specific antigen (PSA) level in men 50-74 years of age with no clinical evidence of prostatic carcinoma, and to test the sensitivity and specificity for cancer detection of these upper limits.
  
  
  METHODS
  A total of 6166 men were recruited for a multicentre study of prostate cancer detection and underwent a serum PSA determination and digital rectal examination (DRE). Men considered to be clinically free of prostatic carcinoma were those with a normal DRE and a PSA level < or = 4.0 ng/mL, and men with an abnormality in either parameter who underwent ultrasonography-guided prostate biopsy that revealed no evidence of carcinoma. By these criteria, 5469 men had no evidence of prostatic carcinoma. Dividing the population into 5-year age increments, three statistical methods were assessed to derive upper limits for serum PSA level by age; the mean +2 SD, the 99th percentile, and a 97.5% prediction interval based on linear regression.
  
  
  RESULTS
  Newly-derived upper limits calculated by each method in the 50-54 and the 70-74 age group were 3.9 ng/mL and 7.6 ng/mL (mean +2 SD), 5.2 ng/mL and 14.0 ng/mL (99th percentile), and 4.7 ng/mL and 8.2 ng/mL (97.5% prediction interval). The sensitivity of the newly-derived upper limits was tested using receiver operating characteristic curves derived from men with no suspicious findings on DRE and a serum PSA concentration > 4.0 ng/mL. Although the specificity of the test increased with increasing PSA upper limits, no upper limits derived from these three methods yielded adequate sensitivity to detect cancer; sensitivities by age range were from 53 to 94%, using mean +2 SD, from 25 to 50% with the 99th percentile, and from 47 to 64% with the 97.5% prediction interval.
  
  
  CONCLUSIONS
  We do not recommend age-referenced adjustments in upper limits for serum PSA concentration, but recommend that an upper limit of 4.0 ng/mL be used in all men 50-74 years of age.
authors.affiliation: Division of Urology, University of Arizona, College of Medicine, Tucson, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Dalkin
authors.forename: F R
authors.initials: FR
authors.lastname: Ahmann
authors.forename: J B
authors.initials: JB
authors.lastname: Kopp
authors.forename: W J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: T L
authors.initials: TL
authors.lastname: Ratliff
authors.forename: M A
authors.initials: MA
authors.lastname: Hudson
authors.forename: J P
authors.initials: JP
authors.lastname: Richie
authors.forename: P T
authors.initials: PT
authors.lastname: Scardino
authors.forename: R C
authors.initials: RC
authors.lastname: Flanigan
authors.forename: J B
authors.initials: JB
authors.lastname: Dekernion
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen