International guidelines recommend a risk-based magnetic resonance imaging (MRI)-directed diagnostic pathway in prostate cancer (PCa) suspected biopsy-naïve men to reduce overdiagnosis. Prostate-specific antigen (PSA) density has been suggested as a stratification tool for MRI or biopsy testing.
This study aims to investigate the risk-based MRI-directed pathway with PSA density thresholds indicating MRI and/or targeted biopsy in PCa suspected men, reducing safely unproductive interventions.
A post hoc analysis was conducted in the MRI arm of the prospective multicentre MR-PROPER study, originally comparing diagnostic outcomes with a risk calculator-based approach. PSA density thresholding strategies were investigated in PCa-suspected biopsy-naïve men undergoing MRI and targeted biopsy for Prostate Imaging Reporting and Data System (PI-RADS) score ≥3. Outcomes were grade group (GG) ≥2 cancer detection, avoided MRI scans, negative biopsies, and GG1 cancer detection, also addressed by benefit-to-harm ratios.
MR-PROPER included 996 PCa-suspected men in the MRI pathway (per-protocol analysis). The GG ≥2 cancer detection rate was 24% (239/996). False MR-positive results were obtained in 47% (217/456; 133 negative biopsies and 84 GG1 cancer cases). In PI-RADS 3 men, post-MRI PSA density thresholding at ≥0.20 ng/ml2 left 1.3% (0-2.7%; 3/239) GG≥2 cancer cases undetected, while avoiding 29% (22-35%; 38/133) negative biopsies and a 3.6% (0-8.2%; 3/84) GG1 cancer detection rate. To indicate MRI, pre-MRI PSA density thresholding at ≥0.10 ng/ml2 avoided 38% (31-44%; 50/133) unproductive biopsies, GG1 cancer detection in 12% (6.1-17%; 10/84), and 30% (27-33%; 301/996) MRI scans, incurring 9.6% (5.4-14%; 23/239) undetected GG ≥2 cancer cases.
In a community-based diagnostic setting (24% GG ≥2 disease), applying a post-MRI PSA density threshold of ≥0.20 rather than the recommended threshold of 0.10 ng/ml2 in men with PI-RADS 3 lesions reduces unnecessary biopsies while maintaining oncological safety. This improved the benefit-to-harm ratio of risk-based PCa diagnostics, particularly in cancer-averse settings. For MRI indication, a pre-MRI PSA density threshold of ≥0.10 ng/ml2 supports a favourable benefit-to-harm ratio, though with narrow safety margins. These findings may inform risk-adapted strategies, particularly in biopsy-averse settings.
European urology oncology. 2025 Nov 28 [Epub ahead of print]
Anne M A Prinsen, Ivo M Wagensveld, Daniel F Osses, Pieter M Groenendijk, Frank M Zijta, Martijn B Busstra, Elena Rociu, Jelle O Barentsz, J P Michiel Sedelaar, Berber Arbeel, Ton Roeleveld, Remy Geenen, Ingrid Koeter, Saskia van der Meer, Vincent C Cappendijk, Sjoerd Klaver, Hans van der Lely, Tineke Wolters, Maicle R Leter, Henk G van der Poel, Stijn W T P J Heijmink, Jos Immerzeel, Joost A P Leijte, Joep G H van Roermund, Razvan L Miclea, Erik Planken, André N Vis, Igle J de Jong, Jasper Tijsterman, Derk Wolterbeek, Anoesjka Claessen, Joost Nederend, Chris H Bangma, Monique J Roobol, Sebastiaan Remmers, Roderick C N van den Bergh, Diederik M Somford, Ivo G Schoots
Department of Urology, Sint Antonius Ziekenhuis, Nieuwegein, The Netherlands., Department of Radiology, Erasmus University Medical Centre, Rotterdam, The Netherlands., Department of Urology, Radboudumc, Nijmegen, The Netherlands., Bergman Clinics, Rijswijk, The Netherlands., Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands., Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands., Department of Radiology, Franciscus Ziekenhuis, Rotterdam, The Netherlands., Andros Clinics, Arnhem, The Netherlands., Department of Urology, Flevoziekenhuis, Almere, The Netherlands., Department of Urology, Northwest Clinics, Alkmaar, The Netherlands., Department of Radiology, Northwest Clinics, Alkmaar, The Netherlands., Department of Urology, Beatrix Ziekenhuis, Gorinchem, The Netherlands., Department of Urology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands., Department of Radiology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands., Department of Urology, Maasstad Ziekenhuis, Rotterdam, The Netherlands., Department of Radiology, Maasstad Ziekenhuis, Rotterdam, The Netherlands., Department of Urology, Deventer Ziekenhuis, Deventer, The Netherlands., Department of Urology, Dijklander Ziekenhuis, Hoorn, The Netherlands., Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Urology, Amsterdam University Medical Centers, Amsterdam, The Netherlands., Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Department of Urology, Amphia Ziekenhuis, Breda, The Netherlands., Department of Urology, Maastricht University Medical Center, Maastricht, The Netherlands., Department of Urology, Admiraal de Ruyter Ziekenhuis, Goes, The Netherlands., Department of Urology, Amsterdam University Medical Centers, Amsterdam, The Netherlands., Department of Urology, Groningen University Medical Center, Groningen, The Netherlands., Department of Urology, Haga Ziekenhuis, The Hague, The Netherlands., Department of Radiology, Haga Ziekenhuis, The Hague, The Netherlands., Department of Urology, Rode Kruis Ziekenhuis, Beverwijk, The Netherlands., Department of Radiology, Catharina Ziekenhuis, Eindhoven, The Netherlands., Department of Urology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands., Department of Radiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41318235