The Case for Prostate Cancer Screening with Prostate-Specific Antigen

From its early use as a marker of prostate cancer progression, prostate-specific antigen (PSA) has matured into a screening test used by many millions of men to aid prostate cancer detection. Despite criticism over its sensitivity/specificity profile, PSA remains the most readily available and most optimal biomarker for prostate cancer. New evidence also suggests that it is a better marker of more aggressive disease, aiding detection of cancers that most urgently require intervention. While we await the outcomes of large-scale, randomised studies to determine the long-term impact of PSA screening on prostate cancer mortality, there is still substantive evidence from nonrandomised data that PSA testing has a positive impact in shifting the presentation of prostate cancer to earlier stages. What is less clear is how a PSA-based screening programme should be implemented and whether the cost-benefit profile is acceptable in some or all countries. Although lowering of the PSA threshold from 4.0 or 3.0 ng/ml has been advocated, the high false-negative rate has real implications at a population level. Furthermore, the burden of increased intervention for early prostate cancer, with its low overall mortality, represents a significant issue for individual men and society alike. It is becoming evident that we need to take a more flexible approach to threshold values, taking into account the age at which screening starts, and using different thresholds and screening intervals to ensure that, first, the lag time to diagnosis is minimised and, second, that "over-testing" is minimised.