TY - JOUR
T1 - 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
AU - Prinsen, Anne M A
AU - Wagensveld, Ivo M
AU - Osses, Daniel F
AU - Groenendijk, Pieter M
AU - Zijta, Frank M
AU - Busstra, Martijn B
AU - Rociu, Elena
AU - Barentsz, Jelle O
AU - Sedelaar, J P Michiel
AU - Arbeel, Berber
AU - Roeleveld, Ton
AU - Geenen, Remy
AU - Koeter, Ingrid
AU - van der Meer, Saskia
AU - Cappendijk, Vincent C
AU - Klaver, Sjoerd
AU - van der Lely, Hans
AU - Wolters, Tineke
AU - Leter, Maicle R
AU - van der Poel, Henk G
AU - Heijmink, Stijn W T P J
AU - Immerzeel, Jos
AU - Leijte, Joost A P
AU - van Roermund, Joep G H
AU - Miclea, Razvan L
AU - Planken, Erik
AU - Vis, André N
AU - de Jong, Igle J
AU - Tijsterman, Jasper
AU - Wolterbeek, Derk
AU - Claessen, Anoesjka
AU - Nederend, Joost
AU - Bangma, Chris H
AU - Roobol, Monique J
AU - Remmers, Sebastiaan
AU - van den Bergh, Roderick C N
AU - Somford, Diederik M
AU - Schoots, Ivo G
PY - 2025/11/28
Y1 - 2025/11/28
N2 - 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/ml 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/ml 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/ml 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/ml supports a favourable benefit-to-harm ratio, though with narrow safety margins. These findings may inform risk-adapted strategies, particularly in biopsy-averse settings.
AB - 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/ml 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/ml 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/ml 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/ml supports a favourable benefit-to-harm ratio, though with narrow safety margins. These findings may inform risk-adapted strategies, particularly in biopsy-averse settings.
KW - Prostate biopsy
KW - Prostate cancer
KW - Prostate magnetic resonance imaging
KW - Prostate-specific antigen density
KW - Risk assessment
U2 - 10.1016/j.euo.2025.11.002
DO - 10.1016/j.euo.2025.11.002
M3 - Article
SN - 2588-9311
JO - European Urology Oncology
JF - European Urology Oncology
ER -