Prostate-specific antigen levels at age 60 years and lifetime risk of lethal prostate cancer

We investigated the natural history of the relationship between prostate-specific antigen (PSA) at age 60 years and lifetime risk of prostate cancer death in an unscreened cohort followed for 40 years in the Malmö Preventive Project. We also investigated whether percent-free PSA could risk-stratify men with low PSAs.

The cohort included 1162 men aged 58-62 years at blood draw in 1981-1982, with 1151 deaths by December 31, 2020. Total and free PSA were measured for 130 men with prostate cancer and 517 without prostate cancer. Lorenz curves were calculated for life years lost to prostate cancer by baseline PSA level.

Total PSA at age 60 years remained highly predictive for full lifetime risk of lethal prostate cancer (C index = 0.87, 95% confidence interval [CI] = 0.82 to 0.92). More than half of the life years lost to prostate cancer in this cohort were in men who had a PSA above 4.0 ng/ml (59%, 95% CI = 54% to 63%) at age 60 years, with 85% (95% CI = 81% to 89%) and 92% (95% CI = 90% to 94%) in men with a PSA above 2.0 ng/ml and above 1.0 ng/ml, respectively. Percent-free PSA did not aid risk stratification in men with low PSA.

Men with a PSA below 1-2 ng/ml at age 60 years are at low risk for lethal prostate cancer and do not require further PSA screening. Unlike a proven role in men with elevated PSA, percent-free PSA is not useful in informing the decision to stop or continue further PSA screening for men with a PSA below 2 ng/ml at age 60 years.