Critical appraisal of prostate-specific antigen in prostate cancer screening: 20 years later.

Prostate-specific antigen (PSA) is secreted by all types of prostate epithelial cells and has been used for 2 decades as a biologic marker for prostate cancer (PCa). Since the implementation of PSA screening in the United States, the detection of PCa has increased, accompanied by a decrease in the incidence of high-grade cancer and PCa-specific mortality rates. It has been suggested that these decreases have resulted from the enhanced detection of PCa while still curable. These data have been the impetus for early detection programs, which have recommended the initiation of screening as early as 40 years of age. Despite widespread use, PSA screening remains controversial, principally because of the lack of evidence from randomized controlled trials demonstrating a mortality benefit that could outweigh the concerns of the costs of overdiagnosis and overtreatment. Two ongoing, randomized controlled trials are examining whether screening reduces the risk of PCa-related mortality, and the results of these studies are expected soon. Although it has its limitations, PSA still remains the best-studied marker for the detection of PCa.