A single, baseline prostate-specific antigen (PSA) level measured at midlife predicted risk of lethal prostate cancer over a 30-year follow-up, according to a nested, case-control study among men who participated in the Physicians’ Health Study.

PSA levels at the 90th percentile and above, compared with levels at the median and lower, were associated with increased risk of lethal prostate cancer (PCa) across all age groups: for men aged 40-49 years, the odds ratio was 8.7 (95% confidence interval, 1.0-78.2), for 50-54 years, 12.6 (1.4-110.4), and for 55-59 years, 6.9 (2.5-19.1). PSA levels above the median were associated with increased risk of all PCa: odds ratios were 7.3 (95% CI, 2.4-21.8) for 40-49 years, 7.6 (3.4-17.2) for 50-54 years, and 10.1 (5.2-19.6) for 55-59 years.

“These data identify subgroups of men, on the basis of their PSA levels at a given age, with widely divergent lifetime risk of PCa death, who therefore could benefit from screening intervals tailored to their actual magnitude of risk,” wrote Dr. Mark Preston of Brigham and Women’s Hospital, Boston, and colleagues (J Clin Oncol. 2016 Jun 13. doi: 10.1200/JCO.2016.66.7527).

The investigators noted that one of seven men with PSA greater than 2.1 mg/mL at 55-59 years and one of 12 men with PSA greater than 2.1 ng/mL at 50-54 years died as a result of PCa within 30 years.

“These findings do not necessarily imply that prostate biopsy or definitive treatment is immediately required in younger men with higher PSA levels at baseline, because this could lead to overdiagnosis, but only that they undergo more intensive PSA screening to enable earlier identification of cancer and potential cure while still possible,” the investigators wrote.

As a subset of the Physicians’ Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene, 14,916 men aged 40-84 years provided a blood sample during 1982-1984. Total PSA was determined from stored specimens, and self-reported incident PCa cases from 1982 to 2012 were confirmed through medical records.

In answer to the question of whether a low PSA level at 40-49 years might safely exempt men from further screening, results showed that for PSA levels below the 25th percentile, cumulative incidence of lethal PCa at 30 years was 0.37% (0.05-1.70) for men 40-44 years and 0.97% (0.30-2.49) for men 45-49 years. Because a small risk remains even with an exceptionally low first measure, another PSA test during the lifetime of men 40-49 is prudent, according to the researchers. At age 60 years, men with PSA below the median are unlikely to develop lethal PCa, based on the analysis.


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