Extending Current Guideline-recommended Prostate-specific Antigen Density Thresholds for Improving Benefit/Harm Balance in Risk-based Magnetic Resonance Imaging-directed Prostate Cancer Diagnosis, from the Community-based Multicentre MR-PROPER Study

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

doi:10.1016/j.euo.2025.11.002

Extending Current Guideline-recommended Prostate-specific Antigen Density Thresholds for Improving Benefit/Harm Balance in Risk-based Magnetic Resonance Imaging-directed Prostate Cancer Diagnosis, from the Community-based Multicentre MR-PROPER Study

Eur Urol Oncol. 2025 Nov 28:S2588-9311(25)00290-1. doi: 10.1016/j.euo.2025.11.002. Online ahead of print.

Authors

Anne M A Prinsen¹, Ivo M Wagensveld², Daniel F Osses³, Pieter M Groenendijk⁴, Frank M Zijta⁵, Martijn B Busstra⁶, Elena Rociu⁷, Jelle O Barentsz⁸, J P Michiel Sedelaar³, Berber Arbeel⁹, Ton Roeleveld¹⁰, Remy Geenen¹¹, Ingrid Koeter¹², Saskia van der Meer¹³, Vincent C Cappendijk¹⁴, Sjoerd Klaver¹⁵, Hans van der Lely¹⁶, Tineke Wolters¹⁷, Maicle R Leter¹⁸, Henk G van der Poel¹⁹, Stijn W T P J Heijmink²⁰, Jos Immerzeel⁸, Joost A P Leijte²¹, Joep G H van Roermund²², Razvan L Miclea⁵, Erik Planken²³, André N Vis²⁴, Igle J de Jong²⁵, Jasper Tijsterman²⁶, Derk Wolterbeek²⁷, Anoesjka Claessen²⁸, Joost Nederend²⁹, Chris H Bangma⁶, Monique J Roobol⁶, Sebastiaan Remmers⁶, Roderick C N van den Bergh⁶, Diederik M Somford³⁰, Ivo G Schoots³¹

Affiliations

¹ Department of Urology, Sint Antonius Ziekenhuis, Nieuwegein, The Netherlands.
² Department of Radiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
³ Department of Urology, Radboudumc, Nijmegen, The Netherlands.
⁴ Bergman Clinics, Rijswijk, The Netherlands.
⁵ Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
⁶ Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands.
⁷ Department of Radiology, Franciscus Ziekenhuis, Rotterdam, The Netherlands.
⁸ Andros Clinics, Arnhem, The Netherlands.
⁹ Department of Urology, Flevoziekenhuis, Almere, The Netherlands.
¹⁰ Department of Urology, Northwest Clinics, Alkmaar, The Netherlands.
¹¹ Department of Radiology, Northwest Clinics, Alkmaar, The Netherlands.
¹² Department of Urology, Beatrix Ziekenhuis, Gorinchem, The Netherlands.
¹³ Department of Urology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands.
¹⁴ Department of Radiology, Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands.
¹⁵ Department of Urology, Maasstad Ziekenhuis, Rotterdam, The Netherlands.
¹⁶ Department of Radiology, Maasstad Ziekenhuis, Rotterdam, The Netherlands.
¹⁷ Department of Urology, Deventer Ziekenhuis, Deventer, The Netherlands.
¹⁸ Department of Urology, Dijklander Ziekenhuis, Hoorn, The Netherlands.
¹⁹ Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Urology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
²⁰ Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
²¹ Department of Urology, Amphia Ziekenhuis, Breda, The Netherlands.
²² Department of Urology, Maastricht University Medical Center, Maastricht, The Netherlands.
²³ Department of Urology, Admiraal de Ruyter Ziekenhuis, Goes, The Netherlands.
²⁴ Department of Urology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
²⁵ Department of Urology, Groningen University Medical Center, Groningen, The Netherlands.
²⁶ Department of Urology, Haga Ziekenhuis, The Hague, The Netherlands.
²⁷ Department of Radiology, Haga Ziekenhuis, The Hague, The Netherlands.
²⁸ Department of Urology, Rode Kruis Ziekenhuis, Beverwijk, The Netherlands.
²⁹ Department of Radiology, Catharina Ziekenhuis, Eindhoven, The Netherlands.
³⁰ Department of Urology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The Netherlands.
³¹ Department of Radiology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Electronic address: i.schoots@erasmusmc.nl.

PMID: 41318235
DOI: 10.1016/j.euo.2025.11.002

Abstract

Background and objective: 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.

Methods: 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.

Key findings and limitations: 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.

Conclusions and clinical implications: 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.

Keywords: Prostate biopsy; Prostate cancer; Prostate magnetic resonance imaging; Prostate-specific antigen density; Risk assessment.