A LARGE population-based cohort study suggests that a single low prostate-specific antigen (PSA) measurement in midlife may identify men at very low risk of developing prostate cancer for up to two decades, supporting more personalised screening strategies.
Researchers analysed data from 2,651 men aged 45–70 years enrolled in the German Study of Health in Pomerania (SHIP), a long-running prospective cohort with up to 20 years of follow-up. The study evaluated whether commonly available clinical factors and liquid biomarkers could help refine risk-adapted prostate cancer screening.
Higher PSA and PSA Density Drive Risk
Over half of participants (55.9%) had baseline PSA levels below 1.00 ng/mL. In this group, cumulative prostate cancer incidence remained low at 0.1% after five years, 0.6% after ten years, and 3.3% at 20 years. By contrast, men with intermediate PSA levels (1.00–3.00 ng/mL) experienced markedly higher rates, with incidence rising to 11.8% at 20 years. The highest-risk group, defined by PSA above 3.00 ng/mL, showed a 20-year incidence of 34.8%.
Statistical modelling identified older age, PSA concentration, and PSA density as the most consistent predictors of long-term risk. Each year of age increased risk modestly, while PSA density demonstrated a particularly strong association. Other clinical variables, including metabolic measures such as body mass index and glycated haemoglobin, showed limited or inconsistent links to prostate cancer incidence.
Implications for Future Screening Strategies
The findings arrive amid growing international interest in organised prostate cancer screening programmes that move away from uniform testing intervals toward risk-stratified approaches. Prostate cancer incidence is projected to rise substantially worldwide by 2040, raising concerns about balancing early detection with the harms of overdiagnosis and unnecessary procedures.
According to the authors, men with very low PSA levels in midlife may safely undergo longer screening intervals, potentially reducing biopsies, imaging, and associated healthcare costs without compromising cancer detection. Conversely, individuals with higher PSA or PSA density may benefit from closer monitoring.
While the observational design limits causal inference, the long follow-up period and population-based sampling strengthen the relevance of the findings for real-world screening strategies. The investigators suggest that integrating simple biomarkers into clinical decision-making could help tailor prostate cancer screening intensity, aligning testing frequency with an individual’s long-term risk profile.
Reference
Lindholz M et al. Clinical and liquid biomarkers of 20-year prostate cancer risk in men aged 45 to 70 years. JAMA Netw Open. 2026; 9(2):e2556732.
