Overdiagnosis and overtreatment of early detected prostate cancer

Early detection of prostate cancer is associated with the diagnosis of a considerable proportion of cancers that are indolent, and that will hardly ever become symptomatic during lifetime. Such overdiagnosis should be avoided in all forms of screening because of potential adverse psychological and somatic side effects. The main threat of overdiagnosis is overtreatment of indolent disease. Men with prostate cancer that is likely to be indolent may be offered active surveillance. Evaluation of active surveillance studies and validation of new biological parameters for risk assessment are expected

A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer Screening in Rotterdam, Netherlands

Background: Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. Methods: The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (≥3 ng ml-1), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. Results: The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason 7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P<0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. Conclusions: Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies

Challenges in longitudinal measurements with HR-pQCT: evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility

Definition of identical regions between repeated computed tomography (CT) scans is a key factor to monitor changes in bone microarchitecture. In longitudinal studies, accurate determination of the volume of interest (VOI), using three dimensional (3D) registration may improve precision. Therefore, the aim of our study was to investigate the short-term reproducibility of bone geometry, density, microstructure and biomechanical parameters assessed by HR-pQCT and micro-finite element (µFE) derived analyses, using the cross-sectional area (CSA) registration method in comparison with the use of 3D registration, to find overlapping regions between scans. Fifteen healthy individuals (aged 21–47 years) underwent 3 separate scans at the distal radius and tibia, within a one-month interval. Reproducibility was assessed after double contouring the cortical compartment and after applying three different methods to determine the common region between repeated scans: (i) the VOI was determined with no registration, i.e., on 110 slices, (ii) the VOI was determined after CSA-based registration, and (iii) the VOI was determined after 3D registration. Both pre- and post-registration short-term reproducibility for each subject was determined. With no registration, CVrms of geometry parameters ranged from 0.5 to 3.7%, showing a slight variation in the CSA between scans. When the CSA registration method was employed, the variability of geometry (CVrms &lt;1.8%) and density parameters (CVrms &lt;1.8%), was better than that obtained without registration. By removing the effect of repositioning, the 3D registration further improved the reproducibility of cortical bone measurements compared to other methods. Indeed, significant improvements were found for cortical geometry and microstructure measurements (CVrms ranged from 0.4% to 10.7% at both sites; p &lt;0.05), whereas the impact on trabecular bone measurements was restricted to its geometry parameter. The repositioning error was significantly reduced, most markedly at the radius compared to the tibia. For µFE measures, the impact of 3D registration on whole bone stiffness was negligible, indicating adequate assessment of longitudinal changes in estimated biomechanical properties, even without registration. In conclusion, we have shown that the 3D registration improved the identification of the common region retained for longitudinal analysis, contributing to improve the reproducibility of cortical bone parameter measurements. We also quantified the minimally detectable bone changes to help designing future studies with HR-pQCT