Diagnostic Strategies for Prostate Cancer

ContextProstate cancer (PCa)is the most common malignancy in men in westernized cultures and the incidence of PCa is rapidly rising in low-risk countries due to significant westernization in these populations. Prostate-specific antigen (PSA) is the gold standard for screening of PCa. Means to improve the specificity and sensitivity of this screening method are imperative.ObjectiveIn this article, we review novel blood-, urine-, and tissue-based biomarkers for screening and early diagnosis of PCa.Evidence acquisitionWe discuss three studies: the 2001 Tyrol study, the European Randomized Study of Screening for Prostate Cancer (ERSPC), and the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.Evidence synthesisThe new molecular forms of PSA, or precursor isoforms (pPSA), are exciting, but further studies are required to validate their clinical application. Measurement of p2PSA, benign PSA (bPSA), and intracellular macrophage PSA (imPSA) proved to be more stable and promising compared to free PSA and serum total PSA, thus improving early diagnosis of PCa, especially in patients with low serum PSA levels. Novel approaches in molecular technology seem to overcome hurdles in detecting PCa cells and markers in urinary samples. Recent results revealed the proteins PCA3 and AMACR to be useful and efficient new tools for PCa detection. PSA density and PSA velocity are certainly superior to a single PSA measurement, and PCa risk calculators may further enhance cancer prediction.ConclusionsThe use of PSA has led to overdiagnosis and overtreatment of PCa, resulting in controversy about its use for screening. PSA also has limited accuracy and poor specificity for early detection of PCa. Novel markers for PCa detection, staging, and monitoring are required.