External Validation of the Prostate Biopsy Collaborative Group Risk Calculator and the Rotterdam Prostate Cancer Risk Calculator in a Swedish Population-based Screening Cohort

Background: External validation of risk calculators (RCs) is necessary to determine their clinical applicability beyond the setting in which these were developed. Objective: To assess the performance of the Rotterdam Prostate Cancer RC (RPCRC) and the Prostate Biopsy Collaborative Group RC (PBCG-RC). Design, setting, and participants: We used data from the prospective, population-based STHLM3 screening study, performed in 2012–2015. Participants with prostate-specific antigen ≥3 ng/ml who underwent systematic prostate biopsies were included. Outcome measurements and statistical analysis: Probabilities for clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology grade ≥2, were calculated for each participant. External validity was assessed by calibration, discrimination, and clinical usefulness for both original and recalibrated models. Results and limitations: Out of 5841 men, 1054 (18%) had csPCa. Distribution of risk predictions differed between RCs; median risks for csPCa using the RPCRC and PBCG-RC were 3.3% (interquartile range [IQR] 2.1–7.1%) and 20% (IQR 15–28%), respectively. The correlation between RC risk estimates on individual level was moderate (Spearman's r = 0.55). Using the RPCRC's recommended risk threshold of ≥4% for finding csPCa, 36% of participants would get concordant biopsy recommendations. At 10% risk cut-off, RCs agreed in 23% of cases. Both RCs showed good discrimination, with areas under the curves for the RPCRC of 0.74 (95% confidence interval [CI] 0.72–0.76) and the PBCG-RC of 0.70 (95% CI 0.68–0.72). Calibration was adequate using the PBCG-RC (calibration slope: 1.13 [95% CI 1.03–1.23]), but the RPCRC underestimated the risk of csPCa (calibration slope: 0.73 [0.68–0.79]). The PBCG-RC showed a net benefit in a decision curve analysis, whereas the RPCRC showed no net benefit at clinically relevant risk threshold levels. Recalibration improved clinical benefit, and differences between RCs