Development of Protein Biomarkers in Post-DRE Urine for use in Liquid Biopsy of Prostate Cancer

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Prostate cancer is a major and growing health problem. Prostate cancer is distinguished from almost every other adult cancer by its remarkable clinical heterogeneity. While some cancer types are almost universally curable (e.g. thyroid cancer), and others are almost universally lethal (e.g. pancreatic cancer), prostate cancers are characterized by their variability. Prostate specific antigen (PSA) is used to screen for prostate cancer, and the introduction of PSA screening detected more low risk cancers than in the “pre-PSA” era. About 40% of newly diagnosed prostate cancers are indolent and will not cause significant health problems during a man’s life. However, the remainder range from intermediate to high risk, and despite definitive local therapy about 10-20% will end up progressing to more aggressive disease. Thus, the key clinical problem in prostate cancer is not early detection of disease, but rather early detection of aggressive disease. African American (AA) men have a significantly higher incidence of prostate cancer overall, along with elevated rates of relapse after definitive local therapy and disease-specific mortality. AA men with low-risk disease who opt for surgery have almost twice the rate of upgrading, and increased frequency of adverse pathologies. These findings have led to a reluctance to recruit AA men onto active surveillance due to concern for presence of aggressive disease. It is also clear that current tissue-based prostate cancer biomarkers perform differently in AA men relative to men of European Ancestry (EA). For example, PTEN loss and ERG expression is less frequent in prostate tumors arising in AA men. It is a general consensus that with the appropriate biomarkers current clinical management strategies can be tailored to achieve ancestral equity. We hypothesize that non-invasive biomarkers developed in men of Caucasian ancestry will not be equally effective in men of AA ancestry and dedicated biomarker development strategies will improve prognosis of AA patients