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Two readers measured the Apparent diffusion coefficient (ADC) of PI-RADS 1\u20135 findings in the peripheral zone. By plotting the cumulative frequency of csPCa versus ADCs and using ROC analysis, we derived four DLs expressing levels of restricted diffusion, i.e., very low DL (VL-DL), low DL (L-DL), intermediate DL (I-DL), and high DL (H-DL). We compared the per-lesion diagnostic performance in assessing csPCa (grading group \u2265\u20092 cancer) assuming to biopsy PI-RADS\u2009\u2265\u20093 lesions (strategy 1), PI-RADS\u2009\u2265\u20093 lesions adjusted with ADC values (strategy 2\u20134), and PI-RADS\u2009\u2265\u20093 lesions adjusted with DLs (strategy 5\u20137). Net benefit was assessed with decision curve analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>csPCa was found in 79\/261 men (30.3%) and 152\/528 lesions (28.8%). There was a negative correlation (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) between ADC versus malignancy rate (tau \u22120.970) and DLs versus csPCa grading group (tau \u22120.614). csPCa prevalence was highest in VL-DL (72.2%) and L-DL (54.4%). Most DLs-based strategies increased specificity, positive predictive value (PPV), and net benefit compared to ADC-based strategies or PI-RADS alone. The best strategy showed 94.7% sensitivity, 82.9% specificity, 69.2% PPV, and 97.5% negative predictive value.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>While larger-scale validation is needed, DLs have the potential to improve PI-RADS-based biopsy decisions for detecting csPCa in the peripheral zone.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key Points<\/jats:title>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Question<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>It is still unclear how to incorporate quantitative information from diffusion-weighted imaging (DWI) into prostate MRI.<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Findings<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>Combining DWI-derived diffusion levels (DLs) with the PI-RADS version 2.1 categorization reduced false positives while preserving high sensitivity for clinically significant prostate cancer.<\/jats:italic>\n            <\/jats:p>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Clinical relevance<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>DLs permit to easily account for ADC values of prostate lesions and, in turn, refine biopsy decisions.<\/jats:italic>\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00330-025-11547-8","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T11:36:51Z","timestamp":1744025811000},"page":"6171-6182","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diffusion levels for quantitative assessment of the apparent diffusion coefficient value in prostate MRI: a proof-of-concept bicentric study"],"prefix":"10.1007","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0904-5147","authenticated-orcid":false,"given":"Rossano","family":"Girometti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Peruzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Clauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"P\u00f6tsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"De Martino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Isola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Giannarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Crestani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Zuiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Cereser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal AT","family":"Baltzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"11547_CR1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.eururo.2015.08.052","volume":"69","author":"JC Weinreb","year":"2016","unstructured":"Weinreb JC, Barentsz JO, Choyke PL et al (2016) PI-RADS Prostate Imaging\u2013Reporting and Data System: 2015, version 2. 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They have not participated in the selection nor review processes for this article. The remaining authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Two of the authors (Maria De Martino and Miriam Isola) are biostatisticians.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Written informed consent was waived by the Institutional Review Board because of the retrospective design.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The study has been approved by the Institutional Review Board (IRB) of the Department of Medicine (DMED) of the University of Udine, with the approval number RIF. Prot. IRB: 263\/2023.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The study population partially overlaps with previous publications without a focus on Diffusion-weighted imaging: (1) Girometti et al []. That study included biopsy-na\u00efve patients only and focused on different PSA-density levels to predict true positivity of prostate target biopsy. (2) Girometti et al []. In this study, we assessed which clinical and imaging variables predict the risk of false positivity of target biopsy. (3) Girometti et al []. In this study, we aimed to assess the impact on biopsy decisions of the Likert score in selectively refining the PI-RADS version 2.1 categorization.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}