The overdiagnosis nightmare: a time for caution

Overdiagnosis (and overtreatment) of cancers not bound to become symptomatic during lifetime is an unavoidable drawback of mammography screening. The magnitude of overdiagnosis has been estimated to be in the range of 5-10%, and thus acceptable in view of screening benefits as to reduced mortality. In a recent research article in BMC Women's Health, Jørgensen, Zahl and Gøtzsche suggest that overdiagnosis may be as high as 33%, based on their analysis of breast cancer incidence in screened and non-screened areas in Denmark. Here we consider how reliable such analyses can be, why it might have been useful to adjust comparisons between screened and non-screened areas for early detection lead time, and what further evidence might be needed to build on or confirm these results

Misclassification of breast cancer as cause of death in a service screening area

Objective: The aim of this study was to assess the misclassification of cause of death for breast cancer cases, and to evaluate the differential misclassification between cases detected in an organized screening program and cases found in current clinical practice. Methods: All deaths occurring between 1999 and 2002 within breast cancer cases were linked to hospital discharge records. Death certificates and latest available hospital discharge notes were classified into various categories. We created a classification algorithm defining which combinations of categories (of death certificates and hospital discharge notes) suggested the probability of misclassification and the need for an in-depth diagnostic review. Questionable cases were reviewed by a team of experts in order to reach a consensus on cause of death. Based on our algorithmic classification and diagnostic review results, the agreement between original cause of death and that resulting from the assessment process was analyzed stratifying for every variable of interest. Results: According to death certificates, breast cancer was the cause of death in 66.9% of subjects, and after assessment this figure changed to 65.7%. The misclassification rate was 4.3% and did not differ significantly between screen-detected (4.7%) and non-screen-detected (4.3%) cases. Higher misclassification rates in favor of false positivity (cause of death wrongly attributed to breast cancer in death certificates) was observed for subjects with multiple cancers (6.5% vs. 1.9%), with no admission in the year before death (4.6% vs. 2.4%) and with an unknown cancer stage (4.9% vs 2.4% or 2.3%). Conclusions: The cause of death misclassification rate is modest, causing a slight overestimate of deaths attributed to breast cancer, and is not affected by modality of diagnosis. The study confirmed the validity of using cause-specific mortality for service screening evaluation. © 2008 Springer Science+Business Media B.V

Change of tumour characteristics and treatment over time in both arms of the European Randomized study of Screening for Prostate Cancer

Objective: To evaluate a change in tumour characteristics and applied treatments over time in the control arm of all centres of the European Randomized study of Screening for Prostate Cancer (ERSPC) and to compare this with similar data of the screening arm. Methods: Between 1993 and 2003, 182,160 men, aged 50-74 years, were randomised to the screening arm (N = 82,816) and the control arm (N = 99,184). Men in the screening arm were offered Prostate Specific Antigen (PSA) testing every 4 years whilst men in the control arm received usual care. Tumour characteristics and treatment were evaluated in all men diagnosed with prostate cancer up to December 2006 or the third screening round. Data on the control arm were divided into 3 periods: 1994-1998, 1999-2002 and 2003-2006. Results: Tumour characteristics were more favourable over time in both the control and the screening arm, with especially increasing proportions of T1C tumours with 29% in 1994-1998 versus 50% in 2003-2006 and 48% at the initial screening round versus 75% at the third screening round, respectively. Tumour characteristics observed in the last period of the control arm were comparable to tumour characteristics in the initial screening round. In the control arm, treatment changed over time with surgery as the most common treatment in the entire observed period, but almost doubling of expectant management and the combination of hormone therapy and radiotherapy over time. In the initial screening round, surgery was the most common treatment (42%), changing over time to expectant management as the most frequently applied treatment in the third screening round (33%). Conclusion: Tumour characteristics in the control arm became more favourable over time and show similarity with prostate cancer cases detected at the initial screening round. The most prominent change in treatment over time was an increase of application of expectan