Overdiagnosis in breast cancer screening: the importance of length of observation period and lead time

Abstract

BackgroundOverdiagnosis in breast cancer screening is a controversial topic. One difficulty in estimation of overdiagnosis is the separation of overdiagnosis from lead time that is the advance in the time of diagnosis of cancers, which confers an artificial increase in incidence when a screening programme is introduced.MethodsWe postulated a female population aged 50-79 with a similar age structure and age-specific breast cancer incidence as in England and Wales before the screening programme. We then imposed a two-yearly screening programme; screening women aged 50-69, to run for twenty years, with exponentially distributed lead time with an average of 40 months in screen-detected cancers. We imposed no effect of the screening on incidence other than lead time.ResultsComparison of age- and time-specific incidence between the screened and unscreened populations showed a major effect of lead time, which could only be adjusted for by follow-up for more than two decades and including ten years after the last screen. From lead time alone, twenty-year observation at ages 50-69 would confer an observed excess incidence of 37%. The excess would only fall below 10% with 25 years or more follow-up. For the excess to be nullified, we would require 30 year follow-up including observation up to 10 years above the upper age limit for screening.ConclusionStudies using shorter observation periods will overestimate overdiagnosis by inclusion of cancers diagnosed early due to lead time among the nominally overdiagnosed tumours.

Were Our Estimates of Overdiagnosis With Mammography Screening 
in the United States “Based on Faulty Science”?

“…The most recent estimate on how long women should be followed after they are screened to thoroughly eliminate lead time bias is 30 years [52].Time of assessment on the RCTs averaged 12 years and ranged from 8 to 19 years (Table 4) www.TheOncologist.com ©AlphaMed Press 2014 Bleyer As to evidence of overdiagnosis of invasive breast cancer per se, we did estimate the frequency of overdiagnosis of invasive breast cancer in our original report [2] under the assumption that all cases of DCIS were overdiagnosed. This analysis suggested that invasive disease accounted for about half of all overdiagnoses and that about 20% of all invasive breast cancers were overdiagnosed, estimates that replicate those of other studies [26].To the extent that less than 100% of DCIS is overdiagnosed, the amount of invasive disease that is overdiagnosed must be proportionately greater.…”

Real and artificial controversies in breast cancer screening

“…To the extent that some overdiagnosis of breast cancer may occur, to be reliable, estimates of overdiagnosis derived from breast cancer incidence rates over time should take account of any longterm underlying trends in incidence taking place independent of screen ing, and of the phenomenon of lead time -that is, the estimate of overdiagnosis should not include cancers detected a few years earlier than they would have been in the absence of screening. It has been pointed out that the most recent and arguably the highest profile publication, that of Bleyer and Welch [5], fails to take full account of underlying incidence trends [8], that the publica tion by Kalager et al [23] fails to fully adjust for lead time [24] and the study of Jørgensen et al [22] has been criticized on both counts [25].…”

“…However, ignor ing these phenomena results in a higher cost to validity than estimating them. Duffy and Par mar [24] show that lead time alone can generate artificial increases in incidence of the order of 30-50%, and that failure to include data up to 10 years after the age that screening ceases will cause overdiagnosis to be overestimated. This suggests that almost all published estimates of overdiagnosis, including our own, exaggerate the problem of excess incidence attributable to screening [2][3][4][5]22,23].…”

Oversimplifying Overdiagnosis

“…3,4 The reason for this is that, because all cancers are latent for at least some time, the introduction of screening always produces a rapid increase in disease incidence. This increase in incidence is attributable to a combination of overdiagnosed cases and non-overdiagnosed cases whose date of detection has been brought forward in time by the screening test.…”

“…However, a simulation study 4 showed that this method may require waiting for many years. A recent report from the Canadian National Breast Screening study 5 waited 10 years after the end of the initial 5-year screening period.…”