title: The impact of reducing the prostate-specific antigen threshold and including isoform reflex tests on the performance characteristics of a prostate-cancer detection programme.
abstract: OBJECTIVE
  To assess the effects on the performance characteristics, in a prostate-cancer detection programme using prostate-specific antigen (PSA) levels, of a lower PSA threshold and the incorporation of reflex (free or complexed PSA) tests.
  
  
  METHODS
  We reviewed publications and extracted data on PSA distributions and performance characteristics of the PSA test and isoform tests from population-based surveys. We estimated the rate of biopsy, cancers detected, and cancers missed that would result from lowering PSA thresholds and including reflex testing.
  
  
  RESULTS
  Lowering the PSA threshold for biopsy referral to 2 ng/mL would increase the number of referrals from 110 to 230 per 1000 men tested, with most of the extra biopsies being among men with no cancer, i.e. an increase from 74 to 172 per 1000 men tested. However, this increased testing would result in an increase in the cancer-detection rate from 3.6% to 5.8%. Including a reflex test for men with moderately elevated PSA levels has little effect on programme performance, with only a modest (10-15%) reduction in unnecessary biopsies and a small increase in the numbers of missed cancers.
  
  
  CONCLUSIONS
  Lowering PSA thresholds, with or without the concurrent introduction of reflex tests, would increase both the numbers of cancers detected and the number of patients referred for biopsy procedures, of which most would be unnecessary. As the extra cancers detected are likely to be clinically localized, and with no evidence that their treatment improves the outcome of the disease, such changes place a possibly unjustified additional burden on the healthcare provider.
authors.affiliation: Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK. andrew.roddam@ceu.ox.ac.uk
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roddam
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Price
mesh_terms: D000368:Aged; D001707:Biopsy, Needle / Q000706:statistics & numerical data; D005188:False Negative Reactions; D005189:False Positive Reactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D020033:Protein Isoforms / Q000378:metabolism; D012016:Reference Values; D012017:Referral and Consultation / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity
chemical_list: D020033:Protein Isoforms; D017430:Prostate-Specific Antigen