Elsevier

European Urology

Volume 74, Issue 2, August 2018, Pages 197-203
European Urology

Prostate Cancer
A Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts

https://doi.org/10.1016/j.eururo.2018.05.003Get rights and content

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Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) utilized data from the 1990s based on six-core biopsies and outdated grading systems.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.

Introduction

The decision to conduct a prostate biopsy for the suspicion of prostate cancer is far from trivial, with potential consequences including sepsis, over-diagnosis of indolent disease or, conversely, delayed diagnosis of an aggressive cancer [1], [2]. The new emphasis on shared-decision making for medical procedures has increased interest in decision tools to allow improved explanation of risk during the physician–patient interaction [3]. Many of the risk tools were developed on large comprehensive cohorts, where statistical modeling integrated the influences of established risk factors, such as prostate-specific antigen (PSA), digital rectal exam (DRE), race, and age, on biopsy outcomes.

Two of the most commonly used risk tools were built on large prospective screening trials: the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk tool and the Prostate Cancer Prevention Trial (PCPT) risk calculator (PCPTRC) [4], [5]. Both trials were performed during the 1990s and hence based on the study populations and clinical practice standards of that time. The PCPT was a heavily screened population of primarily healthy North American white men, requiring a PSA ≤3 ng/ml and a normal DRE to enter the trial, annual PSA and DRE screening, and a required end-of-study biopsy at the end of 7 yr. The ERSPC comprised a near exclusively white European population also heavily screened [6], [7]. These populations are not in accord with contemporary patients from diverse backgrounds who are likely to undergo limited screening during the lifetime and only ever encounter risk assessment after an elevated PSA prompts referral to a tertiary care center. Both the ERSPC and PCPT involved sextant biopsy and grading scheme current in the 1990s. Contemporary biopsies utilize 10–12 twelve cores and are subject to pathologic grading under contemporary schemes that reclassify some cancers to higher Gleason scores [8], [9].

To better understand the relationships between prostate biopsy outcomes and established risk factors in heterogeneous cohorts, the Prostate Biopsy Collaborative Group (PBCG) was formed in 2009 as a consortium collecting retrospective data from 10 screening studies and tertiary referral centers [10]. Validation of both the ERSPC and PCPT risk tools revealed differences in operating characteristics across the cohorts, demonstrating that validation is a property of both the risk tool and the validation cohort [11], [12]. Significant amounts of missing risk factors prohibited robust conclusions and further use from the retrospective data.

To ensure high data quality for production of a new prostate cancer risk tool based on heterogeneous contemporary populations and practice, the PBCG began prospective collection from participating centers in 2014. The new risk tool was to be modeled after the PCPTRC, with the hypothesis that such a risk tool would have better external validation for contemporary populations [13].

Section snippets

Patients and methods

Data from 11 participating sites under local internal review board approval were prospectively collected. Cleveland Clinic, Hamburg, Mayo Clinic, San Raffaele, Zurich, Memorial Sloan Kettering Cancer Center (MSKCC), and University of California San Francisco (UCSF) were participating tertiary referral centers. Durham Veterans Affairs (VA) and San Juan VA served a lower socioeconomic status population with a high percentage of African Americans and Hispanics, respectively. Sunnybrook and UT

Results

We fit the PBCG model on 5992 biopsies from eight institutions in North America and validated it on 10 377 biopsies from three institutions in Europe. Descriptions of the pooled cohorts for fitting and validation are provided in Table 1 and by individual cohort in the Supplementary Appendix. Median age (approximately 65 yr) and PSA (approximately 6 ng/ml) were fairly consistent between cohorts. The rate of positive DRE varied from 13% in MSKCC to 51% in San Juan VA; the proportion of patients

Discussion

The foundation of the North American PBCG risk tool on contemporary North American biopsy patients contrasts that of the PCPTRC, which was built on a healthy predominantly Caucasian population (the PCPT required a PSA ≤4 ng/ml and normal DRE at entry and screened men annually up to 7 yr after) with a required end of study biopsy for all participants regardless of PSA level. One corollary is that only 10% of the PCPT population used to build the PCPTRC had PSA >4 ng/ml; this number exceeded 60%

Conclusions

We have developed an online prostate cancer risk calculator based on multiple, contemporary biopsy cohorts with better performance characteristics compared to one of the currently most widely used online tools, the PCPTRC.

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