Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context

J Natl Cancer Inst. 2009 Mar 18;101(6):374-83. doi: 10.1093/jnci/djp001. Epub 2009 Mar 10.

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Early Detection of Cancer*
  • Europe / epidemiology
  • Humans
  • Incidence
  • Male
  • Mass Screening / adverse effects
  • Mass Screening / methods*
  • Middle Aged
  • Models, Statistical
  • Models, Theoretical*
  • Netherlands / epidemiology
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / epidemiology*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / prevention & control
  • Risk Assessment
  • Risk Factors
  • SEER Program
  • Sensitivity and Specificity
  • Time Factors
  • United States / epidemiology

Substances

  • Biomarkers, Tumor
  • Prostate-Specific Antigen