title: Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context.
abstract: BACKGROUND
  The time by which prostate-specific antigen (PSA) screening advances prostate cancer diagnosis, called the lead time, has been reported by several studies, but results have varied widely, with mean lead times ranging from 3 to 12 years. A quantity that is closely linked with the lead time is the overdiagnosis frequency, which is the fraction of screen-detected cancers that would not have been diagnosed in the absence of screening. Reported overdiagnosis estimates have also been variable, ranging from 25% to greater than 80% of screen-detected cancers.
  
  
  METHODS
  We used three independently developed mathematical models of prostate cancer progression and detection that were calibrated to incidence data from the Surveillance, Epidemiology, and End Results program to estimate lead times and the fraction of overdiagnosed cancers due to PSA screening among US men aged 54-80 years in 1985-2000. Lead times were estimated by use of three definitions. We also compared US and earlier estimates from the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) that were calculated by use of a microsimulation screening analysis (MISCAN) model.
  
  
  RESULTS
  The models yielded similar estimates for each definition of lead time, but estimates differed across definitions. Among screen-detected cancers that would have been diagnosed in the patients' lifetimes, the estimated mean lead time ranged from 5.4 to 6.9 years across models, and overdiagnosis ranged from 23% to 42% of all screen-detected cancers. The original MISCAN model fitted to ERSPC Rotterdam data predicted a mean lead time of 7.9 years and an overdiagnosis estimate of 66%; in the model that was calibrated to the US data, these were 6.9 years and 42%, respectively.
  
  
  CONCLUSIONS
  The precise definition and the population used to estimate lead time and overdiagnosis can be important drivers of study results and should be clearly specified.
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. g.draisma@erasmusmc.nl
authors.forename: Gerrit
authors.initials: G
authors.lastname: Draisma
authors.forename: Ruth
authors.initials: R
authors.lastname: Etzioni
authors.forename: Alex
authors.initials: A
authors.lastname: Tsodikov
authors.forename: Angela
authors.initials: A
authors.lastname: Mariotto
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wever
authors.forename: Roman
authors.initials: R
authors.lastname: Gulati
authors.forename: Eric
authors.initials: E
authors.lastname: Feuer
authors.forename: Harry
authors.initials: H
authors.lastname: de Koning
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D055088:Early Detection of Cancer; D005060:Europe / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008403:Mass Screening / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D015233:Models, Statistical; D008962:Models, Theoretical; D009426:Netherlands / Q000453:epidemiology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D012680:Sensitivity and Specificity; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen