Stockholm3-magnetic resonance imaging population-based prostate cancer screening study: two-year follow-up

Abstract

Prostate-specific antigen (PSA) testing to screen for prostate cancer is controversial. An alternative approach, Stockholm3, combines PSA, plasma protein biomarkers, polygenic risk, and clinical factors into a multivariable risk score. OBJECTIVE: To compare detection of clinically significant prostate cancer (csPC) using PSA and Stockholm3 in a population-based screening with short-term follow-up. DESIGN: Secondary analysis of the baseline round of the prospective STHLM3-MRI (Prostate Cancer Screening Using a Combination of Risk-Prediction, MRI, and Targeted Prostate Biopsies) randomized screening trial in men aged 50 to 74 years who had PSA and Stockholm3 screening. Men with abnormal screening tests (PSA ≥3 ng/mL or Stockholm3 ≥11) were randomly assigned (2:3) to systematic biopsy or magnetic resonance imaging with systematic and targeted biopsies for lesions with a Prostate Imaging Reporting and Data System score of 3 or greater. Cancer diagnosed within 2 years was identified through linkage to the Swedish National Cancer Register; cancer after a negative baseline test was classified as false negative. (ClinicalTrials.gov: NCT03377881). SETTING: Stockholm region, Sweden, 2018 to 2020. PARTICIPANTS: Men aged 50 to 74 years who had PSA and Stockholm3 screening. INTERVENTION: Prostate-specific antigen and Stockholm3 tests at baseline. MEASUREMENTS: Clinically significant prostate cancer (grade group ≥2) within 2 years of baseline. RESULTS: Among 12 670 men, 443 (3.5%) were diagnosed with csPC. Decision curve analysis showed higher net benefit for Stockholm3 versus PSA across a range of decision thresholds for biopsy, indicating fewer unnecessary biopsies and fewer missed csPC cases. Stockholm3 (≥11) had a false-negative rate of 10% (43 of 443) and a false-positive rate of 11% (1289 of 12 227), whereas PSA (≥3 ng/mL) had a false-negative rate of 26% (116 of 443) and a false-positive rate of 10% (1203 of 12 227). Correspondingly, sensitivity was 90% (95% CI, 87% to 93%) for Stockholm3 and 74% (CI, 69% to 78%) for PSA, with similar specificity (89% vs. 90%). LIMITATIONS: Participation was approximately 25% of invited men; follow-up was limited to 2 years; and the cohort was predominantly Swedish or European, which may limit generalizability. CONCLUSION: In this screening cohort with short-term follow-up, Stockholm3 provided greater clinical net benefit than PSA for detecting csPC, driven by fewer false-negative results, although follow-up was limited to 2 years. PRIMARY FUNDING SOURCE: Swedish Research Council, Swedish Prostate Cancer Society, Stockholm Region, and the Swedish Cancer Society.