Prostate cancer (PCA) is a major health concern in current times. Ever since prostate specific antigen (PSA) was introduced in clinical practice almost three decades ago, the diagnosis and management of PCA have been revolutionized. With time, concerns arose as to the inherent shortcomings of this biomarker and alternatives were actively sought. Over the past decade new PCA biomarkers have been identified in tissue, blood, urine, and other body fluids that offer improved specificity and supplement our knowledge of disease progression. This review focuses on superiority of circulating biomarkers over tissue biomarkers due to the advantages of being more readily accessible, minimally invasive (blood) or noninvasive (urine), accessible for sampling on regular intervals, and easily utilized for follow-up after surgery or other treatment modalities. Some of the circulating biomarkers like PCA3, IL-6, and TMPRSS2-ERG are now detectable by commercially available kits while others like microRNAs (miR-21, -221, -141) and exosomes hold potential to become available as multiplexed assays. In this paper, we will review some of these potential candidate circulating biomarkers that either individually or in combination, once validated with large-scale trials, may eventually get utilized clinically for improved diagnosis, risk stratification, and treatment. 1. Introduction In 2014, more than 200,000 American men will be diagnosed with prostate cancer (PCA). It is the most frequently diagnosed solid tumor and the second leading cause of cancer-related deaths amongst men in the United States. It is estimated to cause 28% of the total number of cancer cases and 10% of the total cancer deaths amongst adult male cancer patients. One in 6 men carries a lifetime risk of a PCA diagnosis [1]. Prostate-specific antigen (PSA) is the biomarker currently being used for PCA. PSA-based screening test has been proved to be a useful prognostic tool. Usually high preoperative values have been related to advanced disease and a poorer clinical outcome. Clinicians initially used PSA for monitoring PCA patients after treatment to detect disease progression, treatment failure, or potential relapse [2] and then subsequently recommended its use for screening purposes [3–5]. Since the late 1980s, the introduction of PSA screening along with digital rectal exam (DRE) and transrectal ultrasound (TRUS) in general clinical practice has led to an increase in the documented incidence of PCA [6, 7]. This trend has been accompanied by an increase in invasive procedures with radical prostatectomy rates
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