Identification of Urine Biomarkers to Improve Eligibility for Prostate Biopsy and Detect High-Grade Prostate Cancer

SIMPLE SUMMARY: The screening of prostate cancer (PCa), based on the serum prostate specific antigen (PSA), is characterized by a high number of false positives, leading to overdiagnosis of healthy men and overtreatment of indolent PCa. This clinical problem severely affects the quality of life of patients, who would benefit from more specific risk stratification models. By performing a mass spectrometry (MS) screening on urine samples collected prior to prostate biopsy, we identified novel biomarkers and validated them by ELISA. Here, we show that an upfront urine test, based on quantitative biomarkers and patient age, has a higher performance compared to PSA (AUC = 0.6020) and is a feasible method to improve the eligibility criteria for prostate biopsy, to detect healthy men (AUC = 0.8196) and clinically significant PCa, thereby reducing the number of unnecessary prostate biopsies. ABSTRACT: PCa screening is based on the measurements of the serum prostate specific antigen (PSA) to select men with higher risks for tumors and, thus, eligible for prostate biopsy. However, PSA testing has a low specificity, leading to unnecessary biopsies in 50–75% of cases. Therefore, more specific screening opportunities are needed to reduce the number of biopsies performed on healthy men and patients with indolent tumors. Urine samples from 45 patients with elevated PSA were collected prior to prostate biopsy, a mass spectrometry (MS) screening was performed to identify novel biomarkers and the best candidates were validated by ELISA. The urine quantification of PEDF, HPX, CD99, CANX, FCER2, HRNR, and KRT13 showed superior performance compared to PSA. Additionally, the combination of two biomarkers and patient age resulted in an AUC of 0.8196 (PSA = 0.6020) and 0.7801 (PSA = 0.5690) in detecting healthy men and high-grade PCa, respectively. In this study, we identified and validated novel urine biomarkers for the screening of PCa, showing that an upfront urine test, based on quantitative biomarkers and patient age, is a feasible method to reduce the number of unnecessary prostate biopsies and detect both healthy men and clinically significant PCa.