49 In a comprehensive secondary analysis of the CAP randomised clinical trial, researchers have found that a single invitation for prostate-specific antigen (PSA) screening may slightly reduce prostate cancer mortality over a 15-year period. This study, published in JAMA, provides critical insights into the long-term effects of PSA screening and its implications for public health. The CAP trial, involving 415,357 men aged 50 to 69 years from 573 primary care practices across England and Wales, initially reported no significant effect of PSA screening on prostate cancer mortality after a median follow-up of 10 years. This new analysis extends the follow-up to a median of 15 years, aiming to evaluate the long-term impact of a single PSA screening invitation compared with no screening invitation. Participants in the intervention group received an invitation for a PSA test, with subsequent diagnostic tests if PSA levels were 3.0 ng/mL or higher. The control group received standard practice without any formal invitation for screening. The primary outcomes measured were prostate cancer-specific mortality, all-cause mortality, and the stage and Gleason grade of prostate cancer at diagnosis. The analysis included 98% of the eligible men. Among them, 12,013 men in the intervention group and 12,958 men in the control group were diagnosed with prostate cancer. The 15-year cumulative risk of prostate cancer diagnosis was slightly higher in the intervention group (7.08%) compared to the control group (6.94%). At a median follow-up of 15 years, prostate cancer-specific mortality was 0.69% in the intervention group and 0.78% in the control group. This represents a modest reduction in prostate cancer deaths. But the absolute reduction in deaths was minimal. The study also found that PSA screening led to increased detection of low-grade (Gleason score ≤6) and localized (T1/T2) prostate cancers but did not significantly impact the detection of intermediate or high-grade cancers, or locally advanced or distally advanced tumors. The intervention group had a higher risk of low-grade prostate cancer diagnosis (2.2% vs 1.6%) and a higher risk of localised disease (3.6% vs 3.1%). All-cause mortality rates were similar between the two groups, with 23.2% of men in the intervention group and 23.3% in the control group dying from any cause over the 15-year follow-up. This suggests that while PSA screening may slightly reduce prostate cancer-specific mortality, it does not significantly impact overall survival. The findings of this study have important implications for PSA screening practices. The slight reduction in prostate cancer-specific mortality observed in the intervention group highlights the potential benefit of early detection through PSA screening. Bu the minimal absolute reduction in deaths and the lack of significant impact on all-cause mortality underscore the complexity of PSA screening decisions. The study also points to the need for further research to refine screening strategies, potentially incorporating additional biomarkers or imaging techniques to improve the specificity and effectiveness of prostate cancer screening.