Stockholm3 is a multi-analyte blood test developed for primary prostate cancer (PCa) screening to reduce overdiagnosis and unnecessary testing among men with elevated PSA, while improving detection in men with lower PSA levels. Prior studies have shown a paradoxical U-shaped relationship between PSA and PCa mortality, where men with PSA <2.5–4 ng/mL and higher-grade cancer exhibit higher mortality than those with PSA ≥4 ng/mL adjusting for treatment and other diagnostic features, underscoring the need for more effective screening methods in this group. This study evaluated detection of PCa with Stockholm3 in men with PSA 1.5–3 ng/ml.
All men in Stockholm without prior PCa who underwent Stockholm3 testing outside a trial setting from 2018 were included and linked to the Swedish National Prostate Cancer Registry. Men were followed from test date until diagnosis, death, or emigration, with follow-up through 2023. Cumulative risks of Grade Group (GG) ≥2 PCa were estimated per 100 men annually by Stockholm3 and overall. Alternative grade endpoints were evaluated along with indications for biopsy. Risks in subgroups defined by Stockholm3 risk groups were compared to the total using risk ratios.
In total, 16,358 men were identified undergoing a Stockholm3 screening test with a median age of 61.2 years (IQR: 55.0-67.5), median PSA of 1.74 ng/ml (IQR: 0.86-3.28), with 54.5% attaining ≥12 years of education. Of these 4,441 men (27%) had a PSA between 1.5-3 ng/ml, with 1,247/4,441 (28%) having elevated Stockholm3 risk at baseline. Median follow up was 1.8 years (IQR:1.1-2.1). The incidence of GG≥2 cancer at 2- and 5-years follow-up for the population of men with PSA 1.5-3 ng/ml was 3.53 (3.02-4.12) and 8.17 (6.41-10.43) per 100 men. The RR of being diagnosed with GG≥2 cancer compared to all men with PSA 1.5-3 ng/ml at 5 years was 0.43 (95% CI:0.22-0.83) for men with Stockholm3 <6, 0.85 (95% CI: 0.51-1.42) for men with Stockholm3 6-10 and 1.84 (95% CI: 1.18-2.86) for men with Stockholm3 ≥11.
Men with PCa detected at lower PSA levels often harbor clinically significant disease. These findings suggest that incorporating Stockholm3 into screening can effectively identify men at high risk while minimizing unnecessary evaluation among those with low risk based on PSA alone in men with an intermediate PSA level by contemporary definitions.
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