Total and Free PSA, PCA3, PSA Density and Velocity

Since the late 1980s, the diagnosis and follow-up of prostate cancer (PCa) has relied on the use of prostate-specific antigen (PSA), a blood laboratory measurement that was shown to be associated with pathological diagnosis of cancer and had both diagnostic and prognostic clinical validity and utility. In 1986 the Food and Drug Administration approved the test to monitor those men already diagnosed with cancer, and in 1994 it went further, authorizing the test to help detect cancer in men aged 50 and older. Through the years, PSA has provided significant advancements in diagnosis and prognosis of PCa, although it was counterbalanced by its low sensitivity and specificity. PSA clinical availability triggered a frenzied hunt for the tumor, but its indiscriminate use let critics of the testing, once regarded as heretics, gain credibility. In 2004 the World Health Organization arranged an international consultation to assess new markers recognizing the limitation of PSA testing. Recently, PSA has been thrust into the public spotlight after several publications showed the risk of overdiagnosis and overtreatment of low-risk PCa in particular, which showed that nonperformance of PSA testing would not have affected the longevity or the quality of life. Such shortcoming led urologists to optimized the use of PSA (PSA density and velocity), to investigate some isoforms of PSA (free PSA, [-2]proPSA) and to develop novel molecular markers (PCA3 or molecular markers, i.e., cell cycling processing genes).