To investigate whether prostate cancer screening with prostate-specific antigen (PSA) is beneficial in reducing prostate cancer mortality, and to determine optimal screening intervals and age groups to be screened.

This is a retrospective cohort study of 400,887 men under age 80, with no history of prostate cancer, who had PSA testing at Kaiser Permanente Northern California in the 5 calendar years 1998-2002, and were followed up for 12-16 years. Subjects were stratified into 6 groups based on the screening interval, and into 7 groups based on age. Prostate cancer mortality rates for each of the 42 subgroups were calculated and compared.

The data show that yearly PSA screening is beneficial, reducing prostate cancer deaths by 64% for men aged 55-75 years (95% confidence interval 50-78%, P <.001), and all-cause mortality by 24% (95% confidence interval 15%-34%, P <.001). This is the first study to evaluate various screening intervals and age groups, showing that yearly screening is the interval of choice. No benefit was found for screening at any interval for men under age 55.

Yearly PSA screening is highly effective in reducing both prostate cancer mortality and all-cause mortality in men with prostate cancer, and when combined with active surveillance to prevent overtreatment, lends support for PSA screening for men in good health aged 55-75.