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Publication - Ms Eleanor Walsh

    Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality

    The CAP Randomized Clinical Trial

    Citation

    Martin, R, Donovan, J, Turner, E, Metcalfe, C, Young, G, Walsh, E, Lane, JA, Noble, S, Oliver, S, Evans, S, Sterne, J, Holding, PN, Ben-Shlomo, Y, Brindle, P, Williams, N, Hill, E, Ng, SY, Davis, J, Tazewell, M, Hughes, LJ, Davies, C, Thorn, J, Down, L, Smith, GD, Neal, D, Hamdy, F & , 2018, ‘Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial’. JAMA - Journal of the American Medical Association, vol 319., pp. 883-895

    Abstract

    Importance: Prostate-cancer screening remains controversial because of concerns that potential mortality or quality of life benefits are outweighed by harms from over-detection and subsequent over-treatment.

    Objective: To evaluate the effect of a low-intensity, single PSA screening intervention and standardized diagnostic pathway on prostate cancer specific mortality.

    Design, Setting, Participants: Cluster-randomized clinical trial conducted in 573 general practices (the clusters) across the UK and including 419,582 men aged 50-69 who were randomized between 2001 and 2009. Follow-up was completed March 31, 2016.

    Intervention: An invitation to a single PSA-test versus standard (unscreened) practice.

    Main outcome and measures: Primary outcome: prostate cancer mortality at a median of 10-years’ follow-up, analyzed by intention-to-screen. Pre-specified secondary outcomes: diagnostic stage and grade of prostate cancers identified, all-cause mortality and instrumental variable analysis estimating the causal effect of attending PSA screening.

    Results: Among 415,357 eligible men who were randomized (mean age, 59.0 years), 189,386 men in the intervention-group and 219,439 controls were included in the analysis (n=408,825, 98%). In the intervention-group, 75,707 (40%) attended PSA-testing and 6,857 (4%) had a PSA ≥3-<20ng/ml, of whom 5,850 (85%) had a prostate biopsy. After a median follow-up of 10-years, 549 (0.30 per 1000-person years) men had died from prostate cancer in the intervention group compared with 647 (0.31 per 1000-person years) in the control-group (rate difference -0.013 per 1000-person years, 95%CI -0.047, 0.02; rate-ratio [RR] 0.96, 95%CI 0.85,1.08; p=0.50). The number of prostate cancers diagnosed was higher in the intervention-group (n=8,054; 4.3%) than control-group (n=7,853; 3.6%) (RR 1.19, 95%CI 1.14,1.25; p<0.001). More Gleason grade ≤6 tumors were identified in the intervention than control groups (n=3,263/189,386 [1.7%] vs. n=2,440/219,439 [1.1%]; difference per 1000 = 6.11, 95% CI 5.38, 6.84; p<0.001). In the analysis of all-cause mortality, there were 25,459 deaths in the intervention group, and 28,306 deaths in the control group (RR 0.99, 95%CI 0.94,1.03; p=0.49). In instrumental variable analysis, the adherence-adjusted causal RR for prostate cancer mortality was 0.93 (95%CI 0.67,1.29; p=0.66).

    Conclusion and relevance: Among practices randomized to a low-intensity PSA screening intervention compared with standard practice, there was no significant difference in prostate cancer mortality after a median 10-years follow up, but the detection of low-risk prostate cancers increased. Although longer-term follow-up is in progress, the current findings do not support single PSA-testing for population-based screening.

    Current Controlled Trials number: ISRCTN92187251.

    Full details in the University publications repository