Concerns regarding prostate cancer screening guidelines in minority populations

Prostate-Specific Antigen (PSA) is a first-line recommended serum biomarker used for prostate cancer (PCa) screening. However, this test has critical limitations in specificity within the gray zone of PSA from 4–10 ng/ml. The low specificity for clinically significant Gleason grade group 2–5 (GG2-5) PCa leads to unnecessary negative biopsies, over-detection of indolent cancers, and over-treatment, especially in Black men with favorable risk PCa. The urological community relies on secondary screening tools to augment specificity and increase sensitivity for GG2-5 PCa such as multiparametric magnetic resonance imaging of the prostate (MRI). Current National Comprehensive Cancer Network (NCCN) Early Detection guidelines specifically call for biomarkers and MRI tests to improve the specificity of PSA. Urologists rely on the negative predictive value (NPV) of the secondary screening tools for GG2-5 PCa to defer biopsies for men with elevated PSA. However, the NPV of any threshold chosen decreases in populations with a high prevalence of GG2-5 PCa. For most of these popular secondary biomarkers, specificity and NPV have not been assessed in Black men despite their known high risk. It is necessary to focus on other aspects of accuracy like specificity, NPV and the correlation of predicted risk versus observed risk (i.e., calibration) in populations with both high and low PCa risk (e.g., Black and Asian men). The impact of the new NCCN guideline-supported PSA ≥ 3.0 ng/ml threshold and the currently recommended thresholds of the secondary screening tools should be modeled or prospectively evaluated to see if they provide an acceptable risk-benefit ratio. Beyond discrimination/area under the curve, biomarkers should be evaluated for their calibration, specificity at high sensitivity, and their NPV for men with varied prevalence of GG2-5 PCa before being told to forego prostate biopsy. Clinical, biomarker, and imaging-integrated race stratified risk calculators and statistical modeling can be used to improve screening outcomes in minorities. Guidelines should also involve community providers to better reflect the resource limited settings within the US.