title: Effect of verification bias on screening for prostate cancer by measurement of prostate-specific antigen.
abstract: BACKGROUND
  The sensitivity and specificity of a screening test are biased when disease status is not verified in all subjects and when the likelihood of confirmation depends on the test result itself. We assessed the screening characteristics of the prostate-specific antigen (PSA) measurement after correction for verification bias.
  
  
  METHODS
  Between 1995 and 2001, 6691 men underwent PSA-based screening for prostate cancer. Of these men, 705 (11 percent) subsequently underwent biopsy of the prostate. Under the assumption that the chance of undergoing a biopsy depends only on the PSA-test result and other observed clinical variables, we used a mathematical model to estimate adjusted receiver-operating-characteristic (ROC) curves.
  
  
  RESULTS
  Adjusting for verification bias significantly increased the area under the ROC curve (i.e., the overall diagnostic performance) of the PSA test, as compared with an unadjusted analysis (0.86 vs. 0.69, P<0.001, for men less than 60 years of age; 0.72 vs. 0.62, P=0.008, for men 60 years of age or older). If the threshold PSA value for undergoing biopsy were set at 4.1 ng per milliliter, 82 percent of cancers in younger men and 65 percent of cancers in older men would be missed. A digital rectal examination that is abnormal but not suspicious for cancer does not affect the overall performance characteristics of the test.
  
  
  CONCLUSIONS
  A lower threshold level of PSA for recommending prostate biopsy, particularly in younger men, may improve the clinical value of the PSA test.
authors.affiliation: Joint Center for Radiation Therapy, Harvard Medical School, Boston, USA.
authors.forename: Rinaa S
authors.initials: RS
authors.lastname: Punglia
authors.forename: Anthony V
authors.initials: AV
authors.lastname: D'Amico
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Roehl
authors.forename: Karen M
authors.initials: KM
authors.lastname: Kuntz
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve; D015983:Selection Bias; D012680:Sensitivity and Specificity
chemical_list: D017430:Prostate-Specific Antigen