The PROSA randomized clinical trial was designed to address this gap by testing whether a contrast-free, biparametric MRI (bpMRI)–first screening strategy could improve the early detection of clinically significant disease while maintaining an acceptable balance between benefits, harms, and costs.
Why MRI-First Screening?
Multiple population-based trials have demonstrated that integrating MRI into diagnostic and screening pathways improves early detection of prostate cancer. Importantly, significant cancers may exist even in men with PSA levels traditionally considered “normal.” PROSA specifically explored whether removing PSA as the initial triage test and adopting bpMRI as a primary screening tool could uncover these otherwise missed csPCa cases, without increasing overdiagnosis.
Study Design
PROSA is a prospective, randomized, single-center trial enrolling asymptomatic men aged 49–69 years (≥40 with family history). Participants were randomized to:
- Arm A (MRI-first): bpMRI performed regardless of PSA level;
- Arm B (PSA-based): bpMRI performed only if PSA ≥3 ng/mL (or ≥2.5 ng/mL with family history).
Key Findings
The MRI-first strategy doubled the detection rate of clinically significant prostate cancer compared with the PSA-based pathway (4.6% vs 1.8%), with nearly half of csPCa cases in the MRI-first arm occurring in men with normal PSA levels. Importantly, this increase in detection did not come at the expense of substantially higher clinically insignificant cancer diagnoses, supporting the notion that MRI-first screening preferentially identifies clinically significant disease. The number needed to treat to detect one additional csPCa was 36.
Benefit–harm analyses further favoured MRI-first screening, showing improved grade selectivity (1,89 in Arm A and 1,75 in Arm B), higher biopsy efficiency (0,74 in Arm A and 0,54 in Arm B), and greater biopsy avoidance (23,1 in Arm A and 11,9 in Arm B). Furthermore, the number needed to biopsy to detect one csPCa was 2,35 in Arm A and 2,86 in Arm B. These metrics are increasingly recognized as essential for evaluating screening pathways beyond simple cancer detection rates.
Economic Evaluation
A defining feature of PROSA is its economic evaluation. Using a micro-costing-based HTA approach, the MRI-first strategy demonstrated an incremental cost-effectiveness ratio (ICER) of €2.201,75 per additional csPCa detected, remaining robust across wide sensitivity analyses. When translated into quality-adjusted life years using evidence-based estimates, the incremental cost-utility ratio (ICUR) resulted in €8.468, remaining well below commonly accepted willingness-to-pay thresholds in European healthcare systems.
These findings are particularly relevant given growing concerns about sustainability and resource allocation in population-level screening programs.
Toward Optimized MRI-Based Screening
An exploratory analysis suggested that raising the biopsy threshold to PI-RADS ≥4 could further enhance both clinical and economic efficiency, substantially reducing unnecessary biopsies while missing very few csPCa cases. This supports future risk-adapted strategies, potentially integrating PSA density or family history to refine management of PI-RADS 3 lesions.
Clinical and Policy Implications
PROSA provides pragmatic, real-world evidence that contrast-free MRI-first screening can improve early detection of csPCa, remaining economically sustainable. While longer follow-up is needed to assess downstream outcomes such as mortality reduction and overdiagnosis, these results strengthen the case for rethinking traditional PSA-centric screening paradigms.
As healthcare systems move toward more personalized and value-based care, MRI-based screening strategies may represent a viable next step in prostate cancer early detection and screening.
Written by: Emanuele Messina and Valeria Panebianco
- Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Rome, Italy