{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:48:42Z","timestamp":1791805722104,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>PI\u2010RADS 3 lesions represent a clinical gray zone in prostate cancer diagnostics, often leading to unnecessary biopsies. Additional biomarkers are needed to improve risk stratification and safely exclude clinically significant prostate cancer (csPCa). This study aimed to compare the performance of whole\u2010gland prostate\u2010specific antigen density (PSAD) and transition zone PSA density (TZ\u2010PSAD) in predicting csPCa and to evaluate their clinical utility in biopsy decision\u2010making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single\u2010center retrospective cohort study between 2022 and 2024, including 395 biopsy\u2010na\u00efve patients with PI\u2010RADS 3 lesions on mpMRI. All patients underwent systematic and cognitive targeted prostate biopsy. PSAD and TZ\u2010PSAD were calculated using MRI\u2010derived prostate and transition zone volumes. Clinically significant prostate cancer (csPCa) was defined as ISUP Grade Group \u2265\u20092. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis, and area under the curve (AUC) values were compared using the DeLong test. Optimal cut\u2010off values were determined using the Youden index. Multivariable logistic regression was performed to evaluate predictors, and clinical utility was assessed using 10\u2010fold cross\u2010validated decision curve analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 395 patients, clinically significant prostate cancer (csPCa) was detected in 22 cases (5.6%). In ROC analysis, AUC values were 0.737 for PSA, 0.902 for PSAD, and 0.927 for TZ\u2010PSAD. Both PSAD and TZ\u2010PSAD demonstrated significantly higher discriminative performance than PSA (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), while no statistically significant difference was observed between PSAD and TZ\u2010PSAD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.163). In multivariable analysis, only TZ\u2010PSAD remained statistically significant (OR\u2009=\u20091.06; 95% CI: 1.02\u20131.10;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). Using a TZ\u2010PSAD threshold of \u2265\u20090.331\u2009ng\/mL\n                      <jats:sup>2<\/jats:sup>\n                      , 74.9% of biopsies could be avoided, while the csPCa detection rate among biopsied patients increased to 35.7%. In comparison, a PSAD threshold of \u2265\u20090.15\u2009ng\/mL\n                      <jats:sup>2<\/jats:sup>\n                      resulted in a 65.8% reduction in biopsies with a csPCa detection rate of 19.3%. The number of missed csPCa cases was identical in both strategies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092). Decision curve analysis indicated a potential net clinical benefit of TZ\u2010PSAD over PSAD within low\u2010to\u2010intermediate probability thresholds despite comparable ROC performance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TZ\u2010PSAD demonstrated discriminative performance comparable to PSAD, remained an independent predictor in multivariable analysis, and reduced unnecessary biopsies without compromising the detection of clinically significant prostate cancer in patients with PI\u2010RADS 3 lesions. The zone\u2010specific normalization of PSA may account for PSA elevation related to benign prostatic hyperplasia (BPH) and may facilitate more individualized biopsy decision\u2010making in patients with PI\u2010RADS 3 lesions. These findings suggest that TZ\u2010PSAD may serve as a clinically useful parameter for reducing unnecessary biopsies in patients with PI\u2010RADS 3 lesions; however, further prospective and multicenter studies are warranted to validate its role in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70237","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:09:56Z","timestamp":1787508596000},"page":"1479-1488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of Whole\u2010Gland and Transition Zone PSA Density in Predicting Clinically Significant Prostate Cancer in PI\u2010RADS 3 Lesions"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0439-5532","authenticated-orcid":false,"given":"Mehmet Akif","family":"Do\u011fan","sequence":"first","affiliation":[{"name":"Department of Urology Sivas Numune Hospital Sivas Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6875-0882","authenticated-orcid":false,"given":"H\u00fcseyin","family":"Sayg\u0131n","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine Cumhuriyet University Sivas Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9141-6727","authenticated-orcid":false,"given":"Aydemir","family":"Asdemir","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine Cumhuriyet University Sivas Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9267-2681","authenticated-orcid":false,"given":"\u0130brahim","family":"Karaca","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine Cumhuriyet University Sivas Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9176-8490","authenticated-orcid":false,"given":"Adem","family":"K\u0131r","sequence":"additional","affiliation":[{"name":"Department of Urology G\u00f6ksun State Hospital Kahramanmara\u015f Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0318-0353","authenticated-orcid":false,"given":"Esat","family":"Kor\u011fal\u0131","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine Cumhuriyet University Sivas Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_3_1","unstructured":"M. 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