Applications of Urinary Extracellular Vesicles in the Diagnosis and Active Surveillance of Prostate Cancer

Simple Summary Prostate cancer is the most common cancer among men. Diagnosis and risk stratification of prostate cancer can be challenging due to gaps in our understanding of the disease as well as the limitations of tests used in clinical practice. Extracellular vesicles are microscopic particles containing genetic material, proteins and other molecules that are released by cells. Urine contains extracellular vesicles which can originate from the prostate gland. This review addresses how extracellular vesicles are involved in the development of prostate cancer, as well as how urinary extracellular vesicles can be analysed to diagnose and monitor prostate cancer.Abstract Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge of the underlying biology and natural history of disease development. Urinary extracellular vesicles (EVs) are microscopic, lipid bilayer defined particles released by cells that carry a variety of molecular cargoes including nucleic acids, proteins and other molecules. Urine is a plentiful source of prostate-derived EVs. In this narrative review, we summarise the evidence on the function of urinary EVs and their applications in the evolving field of prostate cancer diagnostics and active surveillance. EVs are implicated in the development of all hallmarks of prostate cancer, and this knowledge has been applied to the development of multiple diagnostic tests, which are largely based on RNA and miRNA. Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology.