Prostate Cancer Screening: Outcomes and Risk Prediction

Abstract

Prostate Cancer Screening: Outcomes and Risk Prediction Maria Frånlund, MD Department of Urology, Institute of Clinical Sciences Sahlgrenska Academy at University of Gothenburg, Sweden ABSTRACT The Göteborg Randomized Population-Based Prostate Cancer (PC) screening trial was started in 1995 to evaluate prostate-specific antigen (PSA) screening and its long-term impact on PC-specific mortality and PC incidence. The four papers included in this thesis present the outcomes of PSA-based screening and also describe aspects of the risk of PC at initial screening, during the 22-year follow-up of the programme, and after termination of screening. In this trial, 10,000 men born 1930–1944 were randomized and thereafter invited to PSA screening every second year from 1995 to 2014. An additional 10,000 men were randomized to the control group (i.e., not invited). The complete incidence of PC was ascertained by linkage to the Swedish Cancer Register and the Swedish Population Register. All relevant medical documentation was retrieved continuously for every man with PC. In our first study (Paper I), we investigated whether men with an elevated PSA level ( 3 ng/mL) and voiding symptoms were at higher risk of PC; the results showed no association between such symptoms and an increased risk of PC. Thereafter (Paper II), we evaluated the long-term outcome in men with an initial PSA of < 3 ng/mL. We concluded that men died from PC despite “normal” baseline PSA and regular participation in the programme. Baseline PSA was strongly associated with long-term PC risk. Free-to-total PSA had no additive value to PSA in this PSA range. In our third study (Paper III), we assessed PC mortality and incidence in the screening and the control group after 22 years of follow-up, which showed that screening reduced PC-specific mortality by 29%. The absolute risk reduction has increased over the years, and the number needed to diagnose is now 9, which is an all-time low (NND=9). High risk of PC death was found in men who did not attend to the programme, men who started testing after the age of 60, and men who had a long life expectancy and terminated screening too early. Paper IV describes our evaluation of outcomes in men who stopped PSA screening after the age of 67–70. We found that participants with a PSA > 1.5 ng/mL (at their final screen) had a non-negligible risk of a future Gleason score of ≥ 7 cancer, and later PC death. Notably, approximately 80% of these cases could have been detected and additional PC deaths prevented, if less than half of all men in the cohort had been offered additional testing (or other diagnostics). Keywords: prostate cancer, screening, prostate-specific antigen, mortality, prediction ISBN: 978-91-7833-121-5 (PRINT), ISBN: 978-91-7833-122-2 (PDF)