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Objectives: To assess the applicability of the Prostate Cancer Prevention Trial High Grade (Gleason grade ≥ 7) Risk Calculator (PCPTHG) in ten international cohorts, representing a range of populations., Methods: A total of 25,512 biopsies from 10 cohorts (6 European, 1 UK and 3 US) were included; 4 implemented 6-core biopsies, and the remaining had 10 or higher schemes; 8 were screening cohorts, and 2 were clinical. PCPTHG risks were calculated using prostate-specific antigen, digital rectal examination, age, African origin and history of prior biopsy and evaluated in terms of calibration plots, areas underneath the receiver operating characteristic curve (AUC) and net benefit curves., Results: The median AUC of the PCPTHG for high-grade disease detection in the 10- and higher-core cohorts was 73.5% (range, 63.9-76.7%) compared with a median of 78.1% (range, 72.0-87.6%) among the four 6-core cohorts. Only the 10-core Cleveland Clinic cohort showed clear evidence of under-prediction by the PCPTHG, and this was restricted to risk ranges less than 15%. The PCPTHG demonstrated higher clinical net benefit in higher-core compared with 6-core biopsy cohorts, and among the former, there were no notable differences observed between clinical and screening cohorts, nor between European and US cohorts., Conclusions: The PCPTHG requires minimal patient information and can be applied across a range of populations. PCPTHG risk thresholds ranging from 5 to 20%, depending on patient risk averseness, are recommended for clinical prostate biopsy decision-making.

Background: The National Comprehensive Cancer Network and American Urological Association guidelines on early detection of prostate cancer recommend biopsy on the basis of high prostate-specific antigen (PSA) velocity, even in the absence of other indications such as an elevated PSA or a positive digital rectal exam (DRE)., Methods: To evaluate the current guideline, we compared the area under the curve of a multivariable model for prostate cancer including age, PSA, DRE, family history, and prior biopsy, with and without PSA velocity, in 5519 men undergoing biopsy, regardless of clinical indication, in the control arm of the Prostate Cancer Prevention Trial. We also evaluated the clinical implications of using PSA velocity cut points to determine biopsy in men with low PSA and negative DRE in terms of additional cancers found and unnecessary biopsies conducted. All statistical tests were two-sided., Results: Incorporation of PSA velocity led to a very small increase in area under the curve from 0.702 to 0.709. Improvements in predictive accuracy were smaller for the endpoints of high-grade cancer (Gleason score of 7 or greater) and clinically significant cancer (Epstein criteria). Biopsying men with high PSA velocity but no other indication would lead to a large number of additional biopsies, with close to one in seven men being biopsied. PSA cut points with a comparable specificity to PSA velocity cut points had a higher sensitivity (23% vs 19%), particularly for high-grade (41% vs 25%) and clinically significant (32% vs 22%) disease. These findings were robust to the method of calculating PSA velocity., Conclusions: We found no evidence to support the recommendation that men with high PSA velocity should be biopsied in the absence of other indications; this measure should not be included in practice guidelines.

Purpose: The relationship between prostate-specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesized that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study., Experimental Design: We used data from five European and three U.S. cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally weighted scatterplot smoothing., Results: The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased the risk of cancer (odds ratio for >6- versus 6-core biopsy, 1.35; 95% confidence interval, 1.18-1.54; P < 0.0005); recent screening led to a smaller increase in risk per unit change in PSA (P = 0.001 for interaction term) and U.S. cohorts had higher risk than the European cohorts (2.14; 95% confidence interval, 1.99-2.30; P < 0.0005)., Conclusions: Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated.

Background: It is difficult to estimate the diagnostic accuracy of biopsy for prostate cancer because men with negative biopsy do not undergo radical prostatectomy and thus have no confirmation of biopsy findings., Methods: We performed 18-core needle biopsies on autopsy prostates from 164 men who had no history of prostate cancer. Six-core biopsies were taken from each of the mid peripheral zone (MPZ), the lateral peripheral zone (LPZ), and the central zone (CZ). We tested associations between age and tumor characteristics and analyzed the sensitivity of biopsies at each site. All statistical tests were two-sided., Results: Prostate cancer was present in 47 (29%) prostates. Of the 47 cancers detected, 20 were clinically significant according to histologic criteria. Tumor volume was associated with tumor grade (P = .012) and with age (P<.001). The biopsies from the CZ did not detect any cancer that was not present in biopsies of either the MPZ or LPZ. The sensitivity of the biopsies taken from the MPZ and LPZ together (53%, 95% confidence interval [CI] = 38% to 68%) was therefore the same as that of 18-core biopsies and was superior to that of biopsies of the MPZ alone (30%, 95% CI = 17% to 45%) (P = .003). The sensitivities of biopsies from the MPZ for clinically significant and insignificant cancer were 55% (95% CI = 32% to 77%) and 11% (95% CI = 2% to 29%), respectively, compared with 80% (95% CI = 56% to 94%) and 33% (95% CI = 17% to 54%) for those from the MPZ and LPZ combined., Conclusions: The ability to detect prostate cancer was more related to the biopsy site than to the number of biopsy cores taken. The 12-core biopsies, six cores each from the MPZ and LPZ, were most likely to detect the majority of clinically significant cancers but also detected many insignificant cancers. When the six-core biopsies from the CZ were added, no increase in sensitivity was observed.