Screening prostate-specific antigen (PSA) levels at midlife could identify men who are at greater risk of developing prostate cancer later in life and who should be monitored more closely. Screening plasma levels of PSA for detection of prostate cancer can benefit prostate cancer prognosis and decrease death rates because of the benefits of early detection.1

This nested, case-control study examined data from the Physicians’ Health Study (PHS), a randomized, placebo-controlled trial examining risk of cardiovascular outcomes and aspirin use. The PHS, begun in 1982, followed physicians for 30 years. Participants provided blood samples at the beginning of the study.

Using data from 234 patients with prostate cancer at age 40 to 59 years and 711 age-matched controls, researchers measured PSA levels from stored plasma samples and examined the men’s outcomes over time. A total of 71 participants developed lethal prostate cancer, and these were re-matched to 213 controls.

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Baseline PSA measures at midlife accurately predicted future risk of prostate cancer. Among the lethal prostate cancer events, 82% of participants at 40 to 49 years, 71% at 50 to 54 years, and 86% at 55 to 59 years had baseline PSA levels significantly above median.

“We found a single baseline PSA-level measurement during midlife could accurately predict future risk of lethal prostate cancer,” said Mark Preston, MD, MPH, a physician in Brigham and Women’s Hospital Division of Urology, Boston, Massachusetts, and co-lead author of this study.

“These data identify subgroups of men, based on their PSA levels at a given age, who could benefit from screening intervals tailored to their actual magnitude of risk.”

In addition, men with a PSA below median (<1.0 ng/mL) at 60 years were significantly less likely to develop lethal prostate cancer in the future.

“These data support the recommendation that risk-stratified screening for prostate cancer based on mid-life PSA should be considered in men aged 45 to 59 [years],” said Lorelei Mucci, ScD, associate professor of epidemiology in the Department of Epidemiology at Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and senior author of this study.

“Our study does not imply prostate biopsy or definitive treatment is immediately required in younger men with higher PSA levels at baseline, as this could lead to over diagnosis. Rather, these men should undergo more intensive PSA screening to enable earlier identification of cancer and potential cure while still possible.”

A few limitations exist for this study. This study population consisted primarily of Caucasians, the lethal events were limited, and an unknown proportion of participants could have undergone opportunistic screening before the study.


1. Preston MA, Batista JL, Wilson KM, et al. Baseline prostate-specific antigen levels in midlife predict lethal prostate cancer [published online June 13, 2016]. J Clin Oncol. doi:10.1200/JCO.2016.66.7527.