Perspective on Prostate Cancer Screening.

Abstract

Undoubtedly, no biomarker has had more profound impact on our approach to cancer detection, staging, and monitoring after treatment than the prostate-specific antigen (PSA)7 test. PSA is a serine protease produced by the prostate epithelium, secreted into seminal fluid, and measurable in peripheral blood by immunoassay laboratory techniques detecting both free unbound forms and that bound to the protease inhibitor α1-antichymotrypsin. The introduction of the PSA test as a diagnostic means to monitor and detect prostate cancer during the 1980s was based on discoveries in the laboratories of Kuriyama, Wang, and Papsidero, together with observations in clinical cohorts never exposed to screening by Stamey, Catalona, and others, noting that men with prostate cancer (or benign prostatic hyperplasia) had higher PSA concentrations compared with healthy controls (1). The PSA test was far more sensitive than assays of prostatic acid phosphatase and digital rectal examination. These findings set off a rapid widespread introduction of the PSA test in clinical practice, mainly in the US, which contributed to a dramatic surge in prostate cancer incidence in the US during the late 1980s through the mid-1990s. There is clear evidence from large population-based randomized trials—the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Goteborg randomized screening trial—that early detection (and concomitant management) by PSA screening reduces a man's risk of dying from prostate cancer. Indeed, extensive use of PSA testing has importantly contributed to a 40% to 50% decline in prostate cancer mortality in the US between 1993 and 2015. However, the widespread use of PSA testing of asymptomatic men, combined with liberal criteria to perform a prostate biopsy, has led to important harms associated with the overdiagnosis of tumors that would never have caused symptoms or harm during a man's lifetime, as well as consequential risk of unnecessary treatment. …