A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts

Abstract

Background: Prostate cancer prediction tools provide quantitative guidance for doctor-patient decision-making regarding biopsy. The widely used online Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) utilized data from the 1990s based on six-core biopsies and outdated grading systems.

Objective: We prospectively gathered data from men undergoing prostate biopsy in multiple diverse North American and European institutions participating in the Prostate Biopsy Collaborative Group (PBCG) in order to build a state-of-the-art risk prediction tool.

Design, setting, and participants: We obtained data from 15 611 men undergoing 16 369 prostate biopsies during 2006-2017 at eight North American institutions for model-building and three European institutions for validation.

Outcome measurements and statistical analysis: We used multinomial logistic regression to estimate the risks of high-grade prostate cancer (Gleason score ≥7) on biopsy based on clinical characteristics, including age, prostate-specific antigen, digital rectal exam, African ancestry, first-degree family history, and prior negative biopsy. We compared the PBCG model to the PCPTRC using internal cross-validation and external validation on the European cohorts.

Results and limitations: Cross-validation on the North American cohorts (5992 biopsies) yielded the PBCG model area under the receiver operating characteristic curve (AUC) as 75.5% (95% confidence interval: 74.2-76.8), a small improvement over the AUC of 72.3% (70.9-73.7) for the PCPTRC (p<0.0001). However, calibration and clinical net benefit were far superior for the PBCG model. Using a risk threshold of 10%, clinical use of the PBCG model would lead to the equivalent of 25 fewer biopsies per 1000 patients without missing any high-grade cancers. Results were similar on external validation on 10 377 European biopsies.

Conclusions: The PBCG model should be used in place of the PCPTRC for prediction of prostate biopsy outcome.

Patient summary: A contemporary risk tool for outcomes on prostate biopsy based on the routine clinical risk factors is now available for informed decision-making.

Keywords: Digital rectal exam; Family history; High-grade disease; Prostate cancer; Prostate-specific antigen; Risk prediction.

Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1

Baseline demographics and univariate odds ratios for association between risk factor and high-grade cancer by cohort. Data not shown for African ancestry for Hamburg, Zurich, San Raffaele, Mayo Clinic, and UCSF. No prior negative biopsy for Hamburg and family history for UCSF because numbers were too low to reliably estimate the odds ratios. DRE = digital rectal exam; MSKCC = Memorial Sloan Kettering Cancer Center; PCPT = Prostate Cancer Prevention Trial; PSA = prostate-specific antigen; UCSF = University of California San Francisco; VA = Veterans Affairs.

Fig. 2

Odds ratios (in favor of endpoint listed to right over left) with 95% confidence intervals for the PBCG and PCPTRC multinomial logistic regression models. DRE = digital rectal exam; PBCG = Prostate Biopsy Collaborative Group; PCPTRC = Prostate Cancer Prevention Trial risk calculator; PSA = prostate-specific antigen.

Fig. 3

Calibration plot showing predicted versus observed risks for the PBCG risk model for high-grade cancer compared to the PCPTRC. Stacked histograms (PBCG on top of PCPTRC) showing distributions of risks from the two models are shown at the bottom. (A) North American cohorts. (B) External validation on European cohorts. PBCG = Prostate Biopsy Collaborative Group; PCPTRC = Prostate Cancer Prevention Trial risk calculator.

Fig. 4

Net benefit curves comparing the PBCG model for high-grade risk to the PCPTRC and the strategy of referring to biopsy all men. (A) North American cohorts. (B) External validation on European cohorts. PBCG = Prostate Biopsy Collaborative Group; PCPTRC = Prostate Cancer Prevention Trial risk calculator.