Validation of the Stockholm3 test for prostate cancer detection in a nationwide Finnish private primary care cohort

OBJECTIVE: The Stockholm3 test combines clinical variables and biomarkers to improve the diagnosis of clinically significant prostate cancer (csPCa). We aimed to validate and compare its performance to prostate-specific antigen (PSA)-based decision-making. MATERIAL AND METHODS: We conducted a prospective observational cohort study at a nationwide Finnish private primary care provider between July 2017 and February 2018. We included 1,379 men scheduled for PSA tests, excluding 74 men with missing PSA results or previously diagnosed prostate cancer. The clinical assessment was based on the PSA value and other clinical parameters, with clinicians unaware of the Stockholm3 result. We compared PSA-based decision-making with counterfactual Stockholm3 reflex testing. RESULTS: Among the 1,305 men, the median age was 58 (interquartile range [IQR]: 51-64). PSA was ≥3 ng/mL in 209/1,305 (16%) men and above the age-specific reference limit in 119/1,305 (9%) men. Among men with PSA ≥1.5 ng/mL, a Stockholm3 Risk Score ≥15% would have selected 44% fewer men for further diagnostic evaluation than PSA ≥3 ng/mL (117/469 vs. 209/469). Over 6 years of registry-based follow-up, men with a Stockholm3 Risk Score ≥15% despite PSA below the age-specific reference limit represented a clinically relevant subgroup with subsequent csPCa diagnoses. The main limitation of this study was its observational design. CONCLUSIONS: The hypothetical clinical implementation of Stockholm3 reflex testing would have reduced referrals, helped standardise decision-making, and identified a different group of men for further diagnostic evaluation.