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.
The PROSA randomised clinical trial evaluates whether a primary biparametric MRI (bpMRI)–first approach can improve prostate cancer (PCa) screening compared with a traditional PSA-gated imaging strategy. In this single-centre Italian study, 759 asymptomatic men aged 49–69 years were randomised either to undergo bpMRI irrespective of PSA levels or to receive MRI only if PSA exceeded conventional thresholds (≥ 3 ng/ml). All participants with PI-RADS scores of 3 or higher underwent targeted fusion biopsy. The study found that the MRI-first strategy resulted in a higher biopsy rate but also in a considerably higher detection rate of clinically significant PCa (4.6% vs 1.8%). Nearly half of the significant tumours detected in the MRI-first arm occurred in men with normal PSA values, highlighting the ability of bpMRI to reveal relevant disease that PSA screening would have missed. Benefit–harm indicators such as grade selectivity and biopsy efficiency were more favourable in the MRI-first arm, while no serious adverse events were reported. Furthermore, a cost-effective analysis demonstrated an incremental cost-effectiveness ratio favouring the MRI-first approach even across wide variations in cost and detection rates.
The PROSA findings raise important considerations for the future landscape of PCa screening and individual early detection. Most opportunistic early detection or screening pathways for PCa diagnostic recommend PSA-gated strategies. However, these may fail to capture a sizeable proportion of significant cancers. PROSA provides real-world confirmation of this concern, observing that almost half of the significant cancers identified by MRI occurred in men with PSA ≤ 3ng/ml. The bpMRI-gated pathway on the other hand, increased the overall number of biopsies. Yet, it did so while improving the ratio of significant to insignificant cancers detected, thereby enhancing the “quality” of diagnostic yield. The results suggest that bpMRI first may offer a more favourable benefit–harm profile than PSA-driven decision-making. However, whether this translates into long-term reductions in overtreatment or improvements in PCa–specific mortality requires further investigation through multi-round or population-based screening trials.
The cost-effectiveness findings provide valuable insight at a time when healthcare systems must justify the expanded use of advanced imaging. While MRI-first screening carries higher upfront imaging expenditures, its ability to detect significant cancers earlier, reduce unnecessary biopsies among MRI-negative men, and potentially shift treatment toward less morbid interventions may offset long-term costs. The cost model used in PROSA supports this possibility, although broader economic analyses across different healthcare environments will be essential.
Thus, the PROSA trial adds pragmatic evidence that primary bpMRI screening could represent a more sensitive, more efficient, and still economically feasible alternative to the long-standing PSA-triggered paradigm.