Prostate CancerA Contemporary Prostate Biopsy Risk Calculator Based on Multiple Heterogeneous Cohorts
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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