Journal of the National Cancer Institute Advance Access published online on March 10, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djp001
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Lead Time and Overdiagnosis in Prostate-Specific Antigen Screening: Importance of Methods and Context
Affiliations of authors: Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, the Netherlands (GD, EW, HdK); Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (RE, RG); Department of Biostatistics, University of Michigan, Ann Arbor, MI (AT); Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD (AM, EF)
Correspondence to: Gerrit Draisma, PhD, Department of Public Health, Erasmus MC, University Medical Center, PO Box 2040 3000 CA, Rotterdam, the Netherlands (e-mail: g.draisma{at}erasmusmc.nl).
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.
| CONTEXT AND CAVEATS Prior knowledge Estimates of lead time, which is the time that screening advances cancer diagnosis, and overdiagnosis, the detection by screening of cancers that would not be detected in the absence of screening, are highly variable for prostate cancer screening using prostate-specific antigen (PSA) testing. Study design Lead times and fractions of overdiagnosis for PSA testing of US men aged 54–80 years in 1985–2000 were estimated using three models of prostate cancer progression and detection calibrated to the Surveillance, Epidemiology, and End Results program. Estimates of lead times using different definitions were compared across models. Contributions Estimated lead times ranged from 5.4 to 6.9 years and were similar across models but different according to the definition used. Overdiagnosis ranged from 23% to 42% of all prostate cancers detected by PSA testing. Implications When reporting lead times in screening studies, the definition of lead time used can impact the outcome and thus should always be specified. Limitations A portion of the PSA screening tests included in the models was likely performed for diagnostic purposes after prostate cancer diagnosis. The estimates are imperfect, and it is unknown in which direction they may be biased. From the Editors
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Manuscript received July 18, 2008; revised December 9, 2008; accepted December 31, 2008.
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J Natl Cancer Inst 2009 101: 361.
J Natl Cancer Inst 2009 101: 361.
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