NOVEL research suggests simple blood-based markers could refine MRI use in prostate cancer detection. Magnetic resonance imaging (MRI) has become central to prostate cancer (PCa) diagnostics, particularly for identifying clinically significant disease and guiding targeted prostate biopsy (PB). However, its routine use in men with a previous negative biopsy remains controversial due to cost, accessibility, and the risk of overinvestigation. A new study explores whether prostate-specific antigen (PSA) derivatives can help clinicians better select patients who truly benefit from MRI, potentially reducing unnecessary imaging.
Defining Optimal PSA, PSAD, and %fPSA Thresholds
Researchers retrospectively analysed 251 men with at least one prior negative PB who underwent serum PSA testing, free PSA measurement, and prostate MRI between October 2015 and June 2024. The study focused on identifying optimal PSA-based thresholds that could guide MRI utilisation while maintaining acceptable detection rates for clinically significant PCa, defined as a Gleason score of ≥7.
Using receiver operating characteristic analysis, the authors identified a Prostate Imaging Reporting and Data System (PI-RADS) score of ≥4 as the most appropriate MRI threshold for predicting clinically significant disease. They then evaluated the predictive performance of three PSA derivatives: total PSA, PSA density (PSAD), and the free-to-total PSA ratio (%fPSA).
The optimal cut-off values were determined to be 11.87 ng/mL for PSA, 0.19 ng/mL² for PSAD, and 18.76% for %fPSA, with all parameters showing strong statistical significance (p<0.001). Notably, the findings suggest that restricting MRI to patients meeting these PSA-based criteria could substantially reduce imaging burden.
According to the authors, limiting MRI use to men with PSA <11.87 ng/mL, PSAD <0.19 ng/mL², or %fPSA >18.76% would reduce MRI utilisation by 22.7%. Importantly, this strategy would miss only 9.1% of clinically significant PCa cases detected through MRI-targeted biopsy, indicating a potentially favourable balance between efficiency and diagnostic safety.
Clinical Implications of PSA Derivatives
The study highlights the clinical value of PSA derivatives as accessible, low-cost tools to support decision-making in a challenging patient population. While MRI remains a powerful diagnostic modality, these findings suggest that a more selective approach, guided by PSA metrics, may be both practical and safe in men with prior negative biopsies.
Further prospective validation is needed, but this research offers a promising strategy to optimise prostate cancer diagnostics while minimising unnecessary investigations.
Reference
Lee S et al. Utility of prostate-specific antigen derivatives to minimize unnecessary magnetic resonance imaging in patients with prior negative prostate biopsy. Sci Rep. 2026;doi: 10.1038/s41598-026-36242-6.
