{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:17:18Z","timestamp":1790223438727,"version":"4.1.0"},"reference-count":112,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Prostate cancer (PCa) is one of the most common malignancies among men worldwide. Current diagnostic methods, such as digital rectal examination (DRE) and prostate\u2010specific antigen (PSA), often lack specificity and lead to overdiagnosis. The Prostate Health Index (PHI), a composite of total PSA, free PSA, and [\u20102]proPSA, has emerged as a promising biomarker for improving PCa detection and risk stratification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This narrative review synthesizes evidence from clinical trials and meta\u2010analyses evaluating the diagnostic and prognostic performance of PHI. Studies on its use in initial and repeat biopsy settings, ethnic variation, integration with multiparametric MRI (mpMRI), and its role in predicting clinically significant PCa were analyzed to provide a comprehensive overview.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PHI consistently demonstrates superior accuracy compared to PSA alone, particularly in the PSA \u201cgray zone\u201d (2\u201310\u2009ng\/mL), reducing unnecessary biopsies while enhancing detection of clinically significant PCa. PHI also shows added value when used in conjunction with mpMRI and risk stratification tools. Ethnic\u2010specific variations suggest the need for population\u2010adjusted reference ranges. Moreover, PHI has shown clinical relevance in predicting Gleason score upgrades and reclassification during active surveillance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PHI is a clinically valuable, noninvasive tool that improves diagnostic precision for PCa, aids in therapeutic decision\u2010making, and may reduce overtreatment. Incorporating PHI into routine clinical practice could optimize PCa management, though further studies are needed to establish standardized thresholds and integrate it into multiparametric diagnostic pathways.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.70025","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T05:29:04Z","timestamp":1754026144000},"page":"1357-1368","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Optimizing Prostate Cancer Care: Clinical Utility of the Prostate Health Index"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8451-0280","authenticated-orcid":false,"given":"I\u2010Ta","family":"Lee","sequence":"first","affiliation":[{"name":"School of Dentistry, College of Oral Medicine Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Ming","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery and Department of Research and Development Taoyuan General Hospital, Ministry of Health and Welfare Taoyuan Taiwan"},{"name":"Department of Urology Xinwu Branch, Taoyuan General Hospital, Ministry of Health and Welfare Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Thuy Tien","family":"Vo","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry Nguyen Tat Thanh University Ho Chi Minh City Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Hua","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Urology National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao\u2010Yuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-8913","authenticated-orcid":false,"given":"Yung\u2010Li","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Oral Medicine Taipei Medical University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6498-4008","authenticated-orcid":false,"given":"Yuh\u2010Lien","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, College of Medicine National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-6791","authenticated-orcid":false,"given":"Chih\u2010Hung","family":"Chiang","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery and Department of Research and Development Taoyuan General Hospital, Ministry of Health and Welfare Taoyuan Taiwan"},{"name":"Department of Urology National Taiwan University Hospital Taipei Taiwan"},{"name":"Division of Urology, Department of Surgery, and Quality Management Center Kaohsiung Veterans General Hospital Kaohsiung Taiwan"},{"name":"Division of Urology, Department of Surgery Kaohsiung Municipal United Hospital Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44197-023-00103-6"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12301-021-00129-x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1370\/afm.2205"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajur.2018.11.007"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2020.01.001"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-040965"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2008.08255.x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2423(08)60334-0"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.5143"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3122\/jabfm.16.2.95"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-016-0268-6"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/aja.2011.141"},{"issue":"3","key":"e_1_2_12_15_1","first-page":"113","article-title":"Twenty Years of PSA: From Prostate Antigen to Tumor Marker","volume":"9","author":"De Angelis G.","year":"2007","journal-title":"Reviews in Urology"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)66519-6"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2003.11.025"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031918"},{"issue":"3","key":"e_1_2_12_19_1","first-page":"756","article-title":"A Precursor Form of Prostate\u2010Specific Antigen Is More Highly Elevated in Prostate Cancer Compared With Benign Transition Zone Prostate Tissue","volume":"60","author":"Mikolajczyk S. D.","year":"2000","journal-title":"Cancer Research"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000000065"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1590\/s1677-5538.ibju.2016.0256"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2010.02.003"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2010.12.032"},{"key":"e_1_2_12_24_1","unstructured":"Premarket Approval (PMA).2024 https:\/\/www.accessdata.fda.gov\/scripts\/cdrh\/cfdocs\/cfpma\/pma.cfm?id=P090026."},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.01.091"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2014.10.121"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.08.010"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2015.08.001"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2018.06.016"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.4178\/epih.e2022088"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2010.08.088"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.06.017"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067687"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.12217"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.195560"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.195784"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2014.02.002"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356240"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22876"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-013-0582-0"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.13139"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.4111\/icu.2016.57.5.336"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.172823"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/21681805.2017.1298155"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23382"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.168687"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/pcan.2016.72"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2018.33.e94"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prnil.2018.02.002"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2018.05.001"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCMA.0000000000000160"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23791"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2019.03.018"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9872146"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja.aja_136_19"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000000495"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2020.04.004"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-78428-6"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13184723"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2021.06.006"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894-021-00897-2"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-020-03585-2"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.864111"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.4111\/icu.20220056"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1159\/000534597"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-023-04860-6"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2024.02.009"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.22465\/juo.234600140007"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-012-0927-9"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.10.047"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2376"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.26896"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.09.042"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.5152\/tud.2017.01058"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000003450"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.7248"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2022.7100"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13712"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1097\/CU9.0000000000000145"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.14098"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-019-02889-2"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-019-02367-z"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000001453"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.901176"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2021-0079-OA"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1068893"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.4111\/icu.20230060"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2023.117270"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.21037\/tau-23-80"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24752"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.133"},{"key":"e_1_2_12_92_1","volume-title":"In: StatPearls [Internet]","author":"Munjal A.","year":"2024"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.06.007"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.06.009"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-013-1566-2"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000002852"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2023.08.011"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18030488"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.06.019"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.13762"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11071912"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2017.08.019"},{"issue":"1","key":"e_1_2_12_103_1","first-page":"3","article-title":"Finding the Wolf in Sheep's Clothing: The 4Kscore Is a Novel Blood Test That Can Accurately Identify the Risk of Aggressive Prostate Cancer","volume":"17","author":"Punnen S.","year":"2015","journal-title":"Reviews in Urology"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.230386"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.7055"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11070664"},{"key":"e_1_2_12_107_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2019.1675515"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.02.3184"},{"key":"e_1_2_12_109_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22898"},{"key":"e_1_2_12_110_1","doi-asserted-by":"publisher","DOI":"10.1038\/pcan.2016.59"},{"key":"e_1_2_12_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.10.029"},{"key":"e_1_2_12_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2016.12.022"},{"key":"e_1_2_12_113_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2022-0354"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:24:04Z","timestamp":1758547444000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.70025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":112,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/pros.70025"],"URL":"https:\/\/doi.org\/10.1002\/pros.70025","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]},"assertion":[{"value":"2025-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}