Background: The harm of screening (unnecessary biopsies and overdiagnosis) generally outweighs the benefit of reducing prostate cancer (PCa) mortality in men aged ≥70 yr. Patient selection for biopsy using risk stratification and magnetic resonance imaging (MRI) may improve this benefit-to-harm ratio. Objective: To assess the potential of a risk-based strategy including MRI to selectively identify men aged ≥70 yr with high-grade PCa. Design, setting, and participants: Three hundred and thirty-seven men with prostate-specific antigen ≥3.0 ng/ml at a fifth screening (71-75 yr) in the European Randomized study of Screening for Prostate Cancer Rotterdam were biopsied. One hundred and seventy-nine men received six-core transrectal ultrasound biopsy (TRUS-Bx), while 158 men received MRI, 12-core TRUS-Bx, and fusion TBx in case of Prostate Imaging Reporting and Data System ≥3 lesions. Outcome measurements and statistical analysis: The primary outcome was the overall, low-grade (Gleason Score 3 + 3) and high-grade (Gleason Score ≥ 3 + 4) PCa rate. Secondary outcome was the low- and high-grade PCa rate detected by six-core TRUS-Bx, 12-core TRUS-Bx, and MRI ± TBx. Tertiary outcome was the reduction of biopsies and low-grade PCa detection by upfront risk stratification with the Rotterdam Prostate Cancer Risk Calculator 4. Results and limitations: Fifty-five percent of men were previously biopsied. The overall, low-grade, and high-grade PCa rates in biopsy naïve men were 48%, 27%, and 22%, respectively. In previously biopsied men these PCa rates were 25%, 20%, and 5%. Sextant TRUS-Bx, 12-core TRUS-Bx, and MRI ± TBx had a similar high-grade PCa rate (11%, 12%, and 11%) but a significantly different low-grade PCa rate (17%, 28%, and 7%). Rotterdam Prostate Cancer Risk Calculator 4-based stratification combined with 12-core TRUS-Bx ± MRI-TBx would have avoided 65% of biopsies and 68% of low-grade PCa while detecting an equal percentage of high-grade PCa (83%) compared with a TRUS-Bx all men approach (79%). Conclusions: After four repeated screens and ≥1 previous biopsies in half of men, a significant proportion of men aged ≥70 yr still harbor high-grade PCa. Upfront risk stratification and the combination of MRI and TRUS-Bx would have avoided two-thirds of biopsies and low-grade PCa diagnoses in our cohort, while maintaining the high-grade PCa detection of a TRUS-Bx all men approach. Further studies are needed to verify these results. Patient summary: Prostate cancer screening reduces mortality but is accompanied by unnecessary biopsies and overdiagnosis of nonaggressive tumors, especially in repeatedly screened elderly men. To tackle these drawbacks screening should consist of an upfront risk-assessment followed by magnetic resonance imaging and transrectal ultrasound-guided biopsy. Repeatedly screened men aged ≥70 yr may still benefit from early prostate cancer detection. Careful patient selection, using multivariable risk stratification and magnetic resonance imaging, is mandatory in these men to tackle the drawbacks of unnecessary biopsies and overdiagnosis of low-grade prostate cancer.

Additional Metadata
Keywords Biopsy, MRI, Multivariable risk stratification, Prostate cancer, Risk calculator, Screening
Persistent URL dx.doi.org/10.1016/j.eururo.2017.06.019, hdl.handle.net/1765/100608
Journal European Urology : Official Journal of the European Association of Urology
Citation
Alberts, A.R, Schoots, I.G, Bokhorst, L.P, Drost, F.-J.H, Leenders, G.J.H.L, Krestin, G.P, … Roobol-Bouts, M.J. (2017). Characteristics of Prostate Cancer Found at Fifth Screening in the European Randomized Study of Screening for Prostate Cancer Rotterdam. European Urology : Official Journal of the European Association of Urology. doi:10.1016/j.eururo.2017.06.019