Serum PSA-based early detection of prostate cancer in Europe and globally: past, present and future

In the pre-PSA-detection era, a large proportion of men were diagnosed with metastatic prostate cancer and died of the disease; after the introduction of the serum PSA test, randomized controlled prostate cancer screening trials in the USA and Europe were conducted to assess the effect of PSA screening on prostate cancer mortality. Contradictory outcomes of the trials and the accompanying overdiagnosis resulted in recommendations against prostate cancer screening by organizations such as the United States Preventive Services Task Force. These recommendations were followed by a decline in PSA testing and a rise in late-stage diagnosis and prostate cancer mortality. Re-evaluation of the randomized trials, which accounted for contamination, showed that PSA-based screening does indeed reduce prostate cancer mortality; however, the debate about whether to screen or not to screen continues because of the considerable overdiagnosis that occurs using PSA-based screening. Meanwhile, awareness among the population of prostate cancer as a potentially lethal disease stimulates opportunistic screening practices that further increase overdiagnosis without the benefit of mortality reduction. However, in the past decade, new screening tools have been developed that make the classic PSA-only-based screening an outdated strategy. With improved use of PSA, in combination with age, prostate volume and with the application of prostate cancer risk calculators, a risk-adapted strategy enables improved stratification of men with prostate cancer and avoidance of unnecessary diagnostic procedures. This combination used with advanced detection techniques (such as MRI and targeted biopsy), can reduce overdiagnosis. Moreover, new biomarkers are becoming available and will enable further improvements in risk stratification. In this Perspective, the authors discuss the past, present and future of PSA screening for the early detection of aggressive prostate cancer and propose a way forward for the rational use of PSA testing as part of a risk-adapted screening strategy.