Primary Noncontrast Magnetic Resonance Imaging for Prostate Cancer Screening: A Randomized Clinical Trial (PROSA)

Background and objective Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) has limited accuracy, and it is linked to overdiagnosis. The PROSA trial aimed to evaluate whether a contrast-free biparametric magnetic resonance imaging (bpMRI)-first screening strategy improves the detection of clinically significant PCa (csPCa) as the primary outcome. The secondary outcomes included overall PCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective. Methods This single-center, randomized controlled trial enrolled 816 asymptomatic men aged 49–69 yr (≥40 yr with a PCa family history). Participants were randomized into two arms: arm A underwent bpMRI regardless of the PSA levels; arm B received bpMRI only if PSA ≥3 ng/ml (or 2.5 ng/ml with a family history). Men with Prostate Imaging Reporting and Data System score ≥3 were directed to a targeted biopsy. Imaging and pathology assessors were blinded; csPCa is defined as International Society of Urological Pathology grade group ≥2. The primary outcomes included csPCa detection, benefit-harm metrics, and cost effectiveness from a health care payer perspective. Key findings and limitations Among 759 randomized men, biopsy and csPCa detection rates were higher in arm A (10.8% and 4.6%, respectively) than in arm B (5.2% and 1.8%, respectively), with a relative risk of 2.6 (95% confidence interval 1.1–6.1; p = 0.05) for the csPCa detection rate. Benefit-harm metrics favored the MRI-first strategy, showing higher grade selectivity (1.89 vs 1.75), biopsy efficiency (0.74 vs 0.54), and biopsy avoidance (23.1 vs 11.9). No serious adverse event was recorded. The MRI-first strategy yielded an incremental cost-effectiveness ratio of €2201.75 per csPCa case detected. Limitations include single-round design and short follow-up. Conclusions and clinical implications In this randomized screening trial, a contrast-free MRI-first pathway improved csPCa detection, enhanced benefit-harm metrics, and showed favorable cost effectiveness.