Young Age on Starting Prostate-specific Antigen Testing Is Associated with a Greater Reduction in Prostate Cancer Mortality: 24-Year Follow-up of the Goteborg Randomized Population-based Prostate Cancer Screening Trial

Background: The risk of death from prostate cancer (PC) depends on age, but the age at which to start prostate-specific antigen (PSA) screening remains uncertain. Objective: To study the relationship between risk reduction for PC mortality and age at first PSA screening. Design, setting, and participants: The randomized Goteborg-1 trial invited men for bien-nial PSA screening between the ages of 50 and 70 yr (screening, n = 10 000) or no invi-tation but exposure to opportunistic PSA testing (control, n = 10 000). Intervention: Regular versus opportunistic PSA screening or no PSA. Outcome measurements and statistical analysis: We modeled the nonlinear association between starting age and the absolute risk reduction in PC mortality in three settings: (1) intention-to-screen (randomized arms); (2) historical control (screening group and 1990-1994 registry data); and (3) attendees only (screening attendees and matched controls). We tested whether the effect of screening on PC mortality depends on the age at starting screening by comparing survival models with and without an interaction between trial arm and age (intention-to-screen and attendees only). Results and limitations: Younger age on starting PSA testing was associated with a greater reduction in PC mortality. Starting screening at age 55 yr approximately halved the risk of PC death compared to first PSA at age 60 yr. The test of association between starting age and the effect of screening on PC mortality was slightly greater than the con-ventional level of statistical significance (p = 0.052) for the entire cohort, and statistically significant among attendees (p = 0.002). This study is limited by the low number of disease-specific deaths for men starting screening before age 55 yr and the difficulty in discriminating between the effect of starting age and screening duration. Conclusions: Given that prior screening trials included men aged up to 70 yr on starting screening, our results suggest that the effect size reported in prior trials underestimates that of currently recommended programs starting at age 50-55 yr. Patient summary: In this study from the Goteborg-1 trial, we looked at the effect of prostate-specific antigen (PSA) screening in reducing men's risk of dying from prostate cancer given the age at which they begin testing. Starting at a younger age reduced the risk of prostate cancer death by a greater amount. We recommend that PSA screen-ing should start no later than at age 55 yr. (c) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.