TOPLINE:

In a population-based cohort study, a single prostate-specific antigen (PSA) measurement in men aged 45-70 years effectively identified individuals with low risk for cancer. Men with PSA levels < 1.00 ng/mL (55.9% of the cohort) had a low cumulative incidence of prostate cancer (3.3%) over 20 years, whereas higher PSA levels were associated with a substantially greater incidence. Older age, higher PSA levels, and higher PSA density were associated with an increased risk of developing prostate cancer.

METHODOLOGY:

• Prostate cancer incidence is rising globally, but opportunistic PSA screening has led to overdiagnosis and unnecessary biopsies, treatment, and other medical harms. Guidelines recommend identifying feasible biomarkers to enable accurate risk stratification and multimodal, population‑based, risk‑adapted prostate cancer screening.
• Researchers analyzed data from 2651 men aged 45-70 years (median age, 54.0 years) in the Study of Health in Pomerania, a prospective population-based research initiative in Germany with structured 20-year follow-up from October 1997 through September 2021. The study also included an imaging subcohort of 1119 men who underwent MRI for prostate volume measurement.
• The risk for prostate cancer was assessed using clinical biomarkers (age, BMI, and waist‑to‑hip ratio), liquid biomarkers (glycated hemoglobin, total cholesterol, triglycerides, high-density lipoprotein, red and white blood cell counts, platelet count, and hemoglobin), serum PSA levels, and PSA density calculated from MRI‑derived prostate volume.
• The primary outcome was long-term prostate cancer incidence, and researchers evaluated its association with baseline clinical and liquid biomarkers. The median follow-up duration was 10.8 years for the overall study cohort and 9.7 years for the imaging subcohort.
• Overall, the median BMI was 28.4, the median waist‑to‑hip ratio was 1.0, and the median serum PSA level was 0.88 ng/mL; in the imaging subcohort, the median prostate volume was 35.0 mL, and PSA density was 0.03 ng/mL².

TAKEAWAY:

• The cumulative incidence of prostate cancer was 1.8%, 4.6%, and 9.1% at 5, 10, and 20 years, respectively. Overall, 55.9% of participants had PSA levels < 1.00 ng/mL; 36.1% had PSA levels 1.00-3.00 ng/mL, and 8.0% had PSA levels > 3.00 ng/mL.
• Among PSA groups, the cumulative incidence of prostate cancer differed significantly. At 20 years, men with PSA levels < 1.00 ng/mL had a low cumulative incidence of 3.3%, those with PSA levels 1.00-3.00 ng/mL had a cumulative incidence of 11.8%, and those with PSA levels > 3.00 ng/mL had a high cumulative incidence of 34.8%.
• In the multivariable analysis, age (hazard ratio [HR], 1.04; P < .001), PSA level (HR, 1.06; P < .001), and PSA density (HR, 1.41; P < .001) showed consistent associations with the risk for prostate cancer. After adjustment, a higher white blood cell count was inversely associated with the risk for prostate cancer (HR, 0.87; P = .02), whereas prostate volume (HR, 1.01; P = .37) and other clinical or biochemical measures — including BMI, glycated hemoglobin levels, and lipid levels — showed no clear or significant association.
• In the imaging subcohort, the 12-year time-dependent area under the curve was 0.86 for PSA with age and 0.75 for PSA density with age, suggesting that PSA with age performed slightly better than PSA density with age.

IN PRACTICE:

This cohort study “found that a low baseline PSA level was associated with low long-term prostate cancer risk,” the authors wrote. “This finding supports longer screening intervals within population-based, risk-adapted programs,” they concluded, adding that “an initial midlife PSA measurement may help focus resources on individuals at greater risk while reducing unnecessary investigations and overdiagnosis.”

SOURCE:

The study, led by Maximilian Lindholz, MD, MS, Charité Universitatsmedizin Berlin in Berlin, Germany, was published online in JAMA Network Open.

LIMITATIONS:

Although the study demonstrated low prostate cancer incidence in men with low PSA levels, researchers were unable to distinguish between clinically significant and insignificant prostate cancer. The whole-body MRI sequence used was not dedicated to prostate imaging or comparable to the sequences recommended in the Prostate Imaging Reporting and Data System for prostate cancer diagnosis, potentially affecting prostate volume and PSA density calculations. Additionally, prostate cancer-specific mortality could not be assessed.

DISCLOSURES:

This study was supported by grants from Siemens Healthineers and fellowships from the BIH Charité (Junior Digital) Clinician Scientist Program funded by the Charité-Universitatsmedizin Berlin, the Berlin Institute of Health, and Stiftung Charité. Several authors reported receiving grants or personal fees and having other ties with various sources. Complete disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.