Importance: Magnetic resonance imaging (MRI) has been proposed to enhance the benefit-to-harm ratio of prostate cancer screening, but data on repeated screening outcomes are lacking.
Objective: To describe outcomes of prostate-specific antigen (PSA)-based screening with MRI and prostate biopsies at repeat screening.
Design, setting, and participants: This secondary analysis examined the population-based, screen-by-invitation STHLM3-MRI randomized clinical trial, which recruited Swedish men aged 50 to 74 years. Men were eligible for repeat screening at 2 to 3 years if they had PSA levels of 1.5 ng/mL or greater at trial inclusion, were randomized to the MRI-targeted group (including screening using biomarkers and MRI), and were not diagnosed with prostate cancer after the first screening round. Repeat screening was performed between November 10, 2021, and February 20, 2023. Data analysis was performed between May and August 2023.
Intervention: Participants underwent blood sampling, including PSA testing. A biparametric MRI scan was performed if PSA levels were 3 ng/mL or greater, and men with lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or greater were referred for targeted and systematic biopsies.
Main outcomes and measures: The primary outcome was clinically significant prostate cancer (Gleason score of ≥3 + 4). Secondary outcomes included the proportion of men with clinically insignificant cancer (Gleason score of 6), the number of elevated PSA tests, MRI scans, and biopsy procedures.
Results: Of 7609 men from the first screening round, 2078 (27.3%) were eligible for and were invited for rescreening. Among the invitees, 1500 (72.2%) participated. Their median age was 67 (IQR, 61-72) years. Of 1094 men with PSA levels between 1.5 and 2.9 ng/mL in the first screening round, 326 (29.8%) had levels of 3 ng/mL or greater in the second round. Overall, 667 men (44.5%) had PSA levels of 3 ng/mL or greater: 617 underwent MRI (92.5%), revealing 51 (7.6%) with equivocal lesions (PI-RADS score of 3) and 33 (4.9%) with suspicious lesions (PI-RADS score of ≥4). Only 10 of 383 men (2.6%) with a prior negative MRI result had a lesion with a PI-RADS score of 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had a Gleason score of 3 + 4 or greater, including 19 (1.3%) with a score of 4 + 3 or greater and 11 (0.7%) with a score of 6.
Conclusions and relevance: In this secondary analysis of the STHLM3-MRI randomized clinical trial, cancer detection during the second screening round in biennial PSA and MRI-based prostate cancer screening was limited, and the detection of low-grade tumors remained low. A substantial proportion of men exhibited elevated PSA levels during rescreening, and a considerable portion of MRI scans performed lacked lesions suggestive of cancer. Future studies should explore strategies to reduce MRI-related resource use.
Trial registration: ClinicalTrials.gov Identifier: NCT03377881.