{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:58:55Z","timestamp":1790258335508,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T00:00:00Z","timestamp":1544572800000},"content-version":"am","delay-in-days":337,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T00:00:00Z","timestamp":1515456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201013\u20101\u20100445"],"award-info":[{"award-number":["W81XWH\u201013\u20101\u20100445"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2018,4]]},"abstract":"\n Objectives<\/jats:title>\n \n To determine the performance of Prostate Health Index (\n PHI<\/jats:styled-content>\n ) density (\n PHID<\/jats:styled-content>\n ) combined with\n MRI<\/jats:styled-content>\n and prior negative biopsy (\n PNB<\/jats:styled-content>\n ) status for the diagnosis of clinically significant prostate cancer (\n PC<\/jats:styled-content>\n a).\n <\/jats:p>\n <\/jats:sec>\n \n Patients and Methods<\/jats:title>\n \n Patients without a prior diagnosis of\n PC<\/jats:styled-content>\n a, with elevated prostate\u2010specific antigen and a normal digital rectal examination who underwent\n PHI<\/jats:styled-content>\n testing prospectively prior to prostate biopsy were included in this study.\n PHID<\/jats:styled-content>\n was calculated retrospectively using prostate volume derived from transrectal ultrasonography at biopsy. Univariable and multivariable logistic regression modelling, along with receiver\u2010operating characteristic (\n ROC<\/jats:styled-content>\n ) curve analysis, was used to determine the ability of serum biomarkers to predict clinically significant\n PC<\/jats:styled-content>\n a (defined as either grade group [\n GG<\/jats:styled-content>\n ] \u22652 disease or\n GG<\/jats:styled-content>\n 1\n PC<\/jats:styled-content>\n a detected in >2 cores or >50% of any one core) on biopsy. Age,\n PNB<\/jats:styled-content>\n status and Prostate Imaging Reporting and Data System (\n PI<\/jats:styled-content>\n \u2010\n RADS<\/jats:styled-content>\n ) score were incorporated into the regression models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of the 241 men who qualified for the study, 91 (37.8%) had clinically significant\n PC<\/jats:styled-content>\n a on biopsy. The median (interquartile range)\n PHID<\/jats:styled-content>\n was 0.74 (0.44\u20131.24); it was 1.18 (0.77\u20131.83) and 0.55 (0.38\u20130.89) in those with and without clinically significant\n PC<\/jats:styled-content>\n a on biopsy, respectively (\n P<\/jats:italic>\n < 0.001). On univariable logistic regression, age and\n PNB<\/jats:styled-content>\n status were associated with clinically significant cancer. Of the tested biomarkers,\n PHID<\/jats:styled-content>\n demonstrated the highest discriminative ability for clinically significant disease (area under the\n ROC<\/jats:styled-content>\n curve [\n AUC<\/jats:styled-content>\n ] 0.78 for the univariable model). That continued to be the case in multivariable logistic regression models incorporating age and\n PNB<\/jats:styled-content>\n status (\n AUC<\/jats:styled-content>\n 0.82). At a threshold of 0.44, representing the 25th percentile of\n PHID<\/jats:styled-content>\n in the cohort,\n PHID<\/jats:styled-content>\n was 92.3% sensitive and 35.3% specific for clinically significant\n PC<\/jats:styled-content>\n a; the sensitivity and specificity were 93.0% and 32.4% and 97.4% and 29.1% for\n GG<\/jats:styled-content>\n \u22652 and\n GG<\/jats:styled-content>\n \u22653 disease, respectively. In the 104 men who underwent\n MRI<\/jats:styled-content>\n ,\n PI<\/jats:styled-content>\n \u2010\n RADS<\/jats:styled-content>\n score was complementary to\n PHID<\/jats:styled-content>\n , with a\n PI<\/jats:styled-content>\n \u2010\n RADS<\/jats:styled-content>\n score \u22653 or, if\n PI<\/jats:styled-content>\n \u2010\n RADS<\/jats:styled-content>\n score \u22642, a\n PHID<\/jats:styled-content>\n \u22650.44, detecting 100% of clinically significant disease. For that subgroup, of the biomarkers tested,\n PHID<\/jats:styled-content>\n (\n AUC<\/jats:styled-content>\n 0.90) demonstrated the highest discriminative ability for clinically significant disease on multivariable logistic regression incorporating age,\n PNB<\/jats:styled-content>\n status and\n PI<\/jats:styled-content>\n \u2010\n RADS<\/jats:styled-content>\n score.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In this contemporary cohort of men undergoing prostate biopsy for the diagnosis of\n PC<\/jats:styled-content>\n a,\n PHID<\/jats:styled-content>\n outperformed\n PHI<\/jats:styled-content>\n and other\n PSA<\/jats:styled-content>\n derivatives in the diagnosis of clinically significant cancer. Incorporating age,\n PNB<\/jats:styled-content>\n status and\n PI<\/jats:styled-content>\n \u2010\n RADS<\/jats:styled-content>\n score led to even further gains in the diagnostic performance of\n PHID<\/jats:styled-content>\n . Furthermore,\n PI<\/jats:styled-content>\n \u2010\n RADS<\/jats:styled-content>\n score was found to be complementary to\n PHID<\/jats:styled-content>\n . Using 0.44 as a threshold for\n PHID<\/jats:styled-content>\n , 35.3% of unnecessary biopsies could have been avoided at the cost of missing 7.7% of clinically significant cancers. Despite these encouraging results, prospective validation is needed.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bju.14098","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T09:03:02Z","timestamp":1513069382000},"page":"619-626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Combining Prostate Health Index density, magnetic resonance imaging and prior negative biopsy status to improve the detection of clinically significant prostate cancer"],"prefix":"10.1111","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4379-3675","authenticated-orcid":false,"given":"Sasha C.","family":"Druskin","sequence":"first","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Tosoian","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Young","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Collica","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-0028","authenticated-orcid":false,"given":"Arnav","family":"Srivastava","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamyar","family":"Ghabili","sequence":"additional","affiliation":[{"name":"Department of Urology Yale School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna J.","family":"Macura","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Department of Radiology and Radiological Sciences Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Ballentine","family":"Carter","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan W.","family":"Partin","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori J.","family":"Sokoll","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley E.","family":"Ross","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore MD USA"},{"name":"Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Pavlovich","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Department of Urology Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/95.12.868"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.12.062"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)37393-7"},{"key":"e_1_2_7_5_1","first-page":"7312","article-title":"PSA density improves prediction of prostate cancer","volume":"21","author":"Verma A","year":"2014","journal-title":"Can J Urol"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2017.04.015"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.195784"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2015.08.001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2013.10.023"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2010.12.032"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.13762"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2016.11.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.3422"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2013.12.005"},{"key":"e_1_2_7_15_1","first-page":"1650","article-title":"Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer","volume":"185","author":"Loeb S","year":"2016","journal-title":"BJU Int"},{"key":"e_1_2_7_16_1","unstructured":"MottetN BellmuntJ BriersEet al.EAU \u2010 ESTRO \u2010 SIOG Guidelines on Prostate Cancer March 2016 update [Internet]. pp.1\u2013146. Available at:https:\/\/uroweb.org\/wp-content\/uploads\/EAU-Guidelines-Prostate-Cancer-2016.pdf. Accessed November 2016"},{"key":"e_1_2_7_17_1","unstructured":"EberhardtSC CarterS CasalinoDDet al.American College of Radiology ACR Appropriateness Criteria: Prostate Cancer \u2014 Pretreatment Detection Staging and Surveillance [Internet].2012. pp.1\u201316. Available at:https:\/\/acsearch.acr.org\/docs\/69371\/Narrative\/. Accessed November 2016"},{"key":"e_1_2_7_18_1","unstructured":"RosenkrantzAB VermaS ChoykePet al.American Urological Association (AUA) Society of Abdominal Radiology (SAR) Joint Consensus Statement: Prostate MRI and MRI\u2010Targeted Biopsy in Patients With Prior Negative Biopsy [Internet].2016. pp.1\u201319. Available at:https:\/\/www.auanet.org\/common\/pdf\/education\/clinical-guidance\/Consensus-Statement-Prostate-MRI-and-MRI-Targeted-Biopsy.pdf. Accessed November 2016"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.05.024"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.03.041"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32401-1"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.03.002"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35364"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/pcan.2016.72"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.08.052"},{"key":"e_1_2_7_26_1","doi-asserted-by":"crossref","unstructured":"EpsteinJI EgevadL AminMBet al.The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.2016: pp.244\u201352.","DOI":"10.1097\/PAS.0000000000000530"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510290050036"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20586"},{"key":"e_1_2_7_29_1","unstructured":"MohlerJL AntonarakisES ArmstrongAJet al.NCCN Clinical Practice Guidelines in Oncology \u2010 Prostate Cancer (2.2017)[Internet]. Available at:http:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/prostate.pdf. Accessed April 2017"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60525-0"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1311593"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113162"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606220"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2015.0183"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2014.10.121"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ucl.2015.08.003"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2012.03.002"}],"container-title":["BJU International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbju.14098","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bju.14098","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bju.14098","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/bju.14098","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bju.14098","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T09:47:19Z","timestamp":1761731239000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/10.1111\/bju.14098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,9]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1111\/bju.14098"],"URL":"https:\/\/doi.org\/10.1111\/bju.14098","archive":["Portico"],"relation":{},"ISSN":["1464-4096","1464-410X"],"issn-type":[{"value":"1464-4096","type":"print"},{"value":"1464-410X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,9]]},"assertion":[{"value":"2018-01-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}