3rd Annual Jefferson Urology Symposium: Men’s Health Forum

© The Canadian Journal of Urology TM : International Supplement, August 2020 25 An overview of biomarkers in the diagnosis and management of prostate cancer overall health and life expectancy, ethnicity, genetic predisposition and pathologic tumor characteristics. In men with elevated PSA > 4 ng/mL, up to 75% will have a negative prostate biopsy. Over the last fewyears biomarker testing has become popular as supplemental tools to aid in decision-making. The use of prostate cancer molecular biomarker analysis of the tumor is now included in guidelines such as in the National Comprehensive Cancer Network (NCCN) for risk stratification and staging of localized disease. Avariety of molecular based tests are commercially available that may provide useful adjunctive information at various stages in the prostate cancer pathway including diagnosis, primary treatment or adjuvant therapy. The presentation, summarized here, provided a basic overview of the biomarker tests that are currently available, stratified by indication for each specific test, Figure 1. For patients with clinical suspicion of prostate cancer who are considering biopsy Prostate Health Index (PHI ) (Beckman Coulter, Brea, California, USA) score is an FDA approved blood test that takes into account multiple proteins including PSA, free PSA and pro2PSA in a single formulated value that is more specific for prostate cancer than PSA alone. It is indicated for menwith no prior biopsy who have a PSA between 4-10 ng/mL and non-suspicious DRE. It has been associated with both the presence of prostate cancer on biopsy, and a Gleason score of 4+3 or greater. It also reduces the rate of negative biopsy. PHI is reported in one of four categories correlating with increased probability of cancer. 8,9 Progensa Prostate cancer gene 3 (PCA3) (Hologic, Marlborough, Massachusetts, USA) is a urine based biomarker collected after DRE for use in men with suspected prostate cancer before initial biopsy or after prior negative biopsy. PCA3 is a prostate specific protein not expressed in other tissues or cancers, and is overexpressed by prostate cancer cells. Unlike PSA, it is unrelated to overall prostate size, and unchanged by 5 alpha-reductase inhibitor status. It has been suggested that for biopsy naïve patients, PCA3 > 60 increases likelihood that cancer will be detected, and a value < 20 has a high negative predictive value for cancer presence. 11-15 Select MDx (MDxHealth, Irvine, California, USA) is a non-invasive urine methylation assay for biopsy naïve men with an elevated PSA and/or DRE that produces a likelihood of detecting prostate cancer on biopsy (illustratedby a percentage). Itmeasures urinarymRNA levels of HOXC6 and DLX1 proteins; higher levels are associated with increased probability of having aggressive cancer. This test predicts Gleason ≥ 7 disease with 98% negative predictive value (NPV) and Gleason ≥ 8 diseasewith 99%NPVandhas been shown to reduce the number of unnecessary biopsies by up to 53%. 3 ExoDx IntelliScore (Exosome Diagnostics, Cambridge, Massachusetts, USA) is a validated urine test in men over 50 years old who are scheduled for initial prostate biopsy with PSA levels 2-10 ng/mL to predict the likelihood of harboring grade group 2 or greater cancer. It is a standalone result calculated solely from exosome gene expressionwith exclusion of clinical parameters to produce a lowor high risk score. Using a validated pre- determined cut off point of 15.6, the test has a negative predictive value > 90%, and a sensitivity of 92%. 16 Figure 1. Clinical applications of some commonly used biomarkers in prostate cancer. 4K score (OPKO Hea l th , Elmwood Park, New Jersey, USA) is a blood based test that considers 4 kallikreins (total PSA, free PSA, intact PSA, hK2) as well as clinical information (age, DRE, prior biopsy results) in an algorithm to predict aggressive prostate cancer. It is reported as a percentage of having Gleason ≥ 7 disease. It also stratifies the 20 year risk of developing metastatic disease and prostate cancer mortality. It is indicated in men considering initial biopsy or those with prior negative biopsy with ongoing clinical suspicion of cancer. 10