Prostate Cancer (PCa) is one of the most common malignancies of men. The incidence rates are especially high in developed countries, which have the oldest population profiles and, therefore, increased risk of prostate cancer (around 6 in 10 prostate cancers cases are diagnosed in men over the age of 65).The diagnostic incidence of prostate cancer across the US, France, Germany, Italy, Spain, UK, Japan, Brazil, and Canada is expected to increase at an Annual Growth Rate (AGR) of 3.6 per cent from 2013 to 2023 (GlobalData Report, 2015).
Thus, the diagnostic and screening market for prostate cancer is estimated to reach over US$17 billion by 2017 (BCC Research, 2013). The unmet need for reliable and highly-specific diagnostic tools indicates a requirement for new diagnostic approaches aimed at overcoming the two main problems associated with current Prostate Specific Antigen (PSA)-based testing: high over-diagnosis rates and inability to predict aggressive disease.
Current Standard for Early Detection
Prostate cancer can be detected at early stages by Digital Rectal Examination (DRE) or the PSA test. During the DRE a doctor inserts a gloved finger into the rectum to feel the prostate surface for swelling, harder areas or lumps that can indicate the presence of a tumour. Men with abnormal DRE should be referred to an urologist for further testing, regardless of PSA results. PSA, a serine protease kallikrein protein secreted by the prostate epithelial cells, is involved in seminal liquefaction. PSA testing measures the levels of this protein in blood. Normally, serum PSA levels are low in healthy men, but they increase if there is a disruption of the basement membrane of the prostate gland (e.g. during prostate cancer) and PSA is released into the peripheral circulation. PSA levels under 4 ng/mL are considered ‘normal’; levels between 4 and 10 ng/mL are considered ‘intermediate’, with cancer present in 30-35 per cent of patients; and PSA levels over 10 ng/mL are considered ‘high’, with a 67 per cent probability of advanced disease (National Comprehensive Cancer Network, 2016). DRE and PSA tests are only indicators of cancer risk and, if abnormal results are obtained, a biopsy is often recommended to examine prostate tissue samples for cancer cells. If cancer cells are present, the pathologist will assign a Gleason score on a scale of 2 to 10, based on the appearance of cancer cells compared to normal cells, to help evaluate the prognosis of patients.
The Need for Better Diagnostic Tests
Despite PSA having been considered the gold-standard biomarker for the detection of prostate cancer for almost two decades, PSA screening has led to a high rate of over-diagnosis resulting in men with indolent disease undergoing unnecessary biopsies and subsequent treatment (Etzioni et al., 2002). This is because PSA is not specific for prostate cancer, and can be elevated in other prostate conditions, such as prostatitis or Benign Prostatic Hyperplasia (BPH).
PSA Derivatives and Isoforms