{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:45:23Z","timestamp":1773211523158,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Early detection of prostate cancer (PCa) enables timely therapeutic intervention and improved clinical outcomes. Screening strategies are increasingly individualized and now incorporate multiparametric MRI findings, reported using the Prostate Imaging Reporting and Data System (PI-RADS), to refine biopsy decision-making. PROSTest is a novel machine learning (ML)-enhanced, 30-gene mRNA liquid biopsy assay developed to detect PCa from whole blood. In this prospective study (NCT06872619), we evaluated whether PROSTest could function as a pre-biopsy triage tool to inform biopsy decisions while preserving sensitivity for clinically significant prostate cancer (csPCa). Methods: Of 121 men evaluated, 111 (91.7%) completed the full diagnostic work-up\u2014including PSA testing, PROSTest analysis, and PI-RADS assessment\u2014and subsequently underwent image-guided biopsy. Peripheral blood samples for PROSTest were collected prior to biopsy. RNA-stabilized samples underwent RNA isolation followed by reverse transcription and quantitative PCR. Gene expression data were processed using a proprietary machine learning algorithm to generate a continuous range from 0 to 100. A clinically validated cut-off \u2265 50 was applied to produce a binary (positive\/negative) result. The diagnostic accuracy of PROSTest was assessed against histology-confirmed prostate cancer. Results: The median age of participants was 69 years (47\u201383 years) and the median PSA was 7.5 ng\/mL (IQR: 5.8\u201311.4 ng\/mL); most patients (104 of 111; 93.7%) had a PI-RADS score of three to five. PCa was diagnosed in 97 men (87.4%) including eight in ISUP Grade Group (GG) 1, 46 in GG2, 33 in GG3, three in GG4 and seven in GG5. PROSTest was positive in 102\/111 (91.9%). Among men with biopsy-confirmed PCa, diagnostic accuracy was 99% (93\/94). Of the 17 men without histologic evidence of disease, eight (47%) were PROSTest-negative. The overall accuracy was 91% (84.1\u201395.6%) with an NPV of 89% (51.6\u201398.4%). Among the nine patients with positive PROSTest but negative biopsy, PI-RADS scores were 4 (n = 6), 3 (n = 1), and 2 (n = 2). Conclusions: PROSTest demonstrated an overall accuracy of 91% (95% CI: 84.1\u201395.6%) with an NPV of 89%. Among men without a detectable prostate cancer on biopsy, 47% (8\/17) were PROSTest-negative. These results suggest that PROSTest may serve as a useful pre-biopsy triage assay.<\/jats:p>","DOI":"10.3390\/cancers18050871","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:49:42Z","timestamp":1773071382000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Utility of PROSTest: A Prospective Study Suggesting Reduction in Unnecessary MRI and Biopsy in Men Evaluated for Prostate Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4591-4055","authenticated-orcid":false,"given":"Kambiz","family":"Rahbar","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital Muenster, 48149 Muenster, Germany"},{"name":"West German Cancer Centre Muenster (WTZ), 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-4446","authenticated-orcid":false,"given":"Martin","family":"B\u00f6gemann","sequence":"additional","affiliation":[{"name":"West German Cancer Centre Muenster (WTZ), 48149 Muenster, Germany"},{"name":"Department of Urology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Papavasilis","sequence":"additional","affiliation":[{"name":"West German Cancer Centre Muenster (WTZ), 48149 Muenster, Germany"},{"name":"Department of Urology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdel","family":"Halim","sequence":"additional","affiliation":[{"name":"Wren Laboratories, Branford, CT 06405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1525-5167","authenticated-orcid":false,"given":"Mark","family":"Kidd","sequence":"additional","affiliation":[{"name":"Wren Laboratories, Branford, CT 06405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"ref_1","first-page":"CD004720","article-title":"Screening for prostate cancer","volume":"2013","author":"Illic","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.7326\/0003-4819-157-2-201207170-00459","article-title":"Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement","volume":"157","author":"Moyer","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"ref_3","unstructured":"(2025). GBD 2023 Causes of Death Collaborators. Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990\u20132023, a systematic analysis for the Global Burden of Disease Study 2023. Lancet, 406, 1811\u20131872."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/glycob\/cwg041","article-title":"Altered Glycosylation Pattern Allows the Distinction Between Prostate-Specific Antigen (PSA) from Normal and Tumor Origins","volume":"13","author":"Peracaula","year":"2003","journal-title":"Glycobiology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1056\/NEJM199104253241702","article-title":"Measurement of prostate-specific antigen in serum as a screening test for prostate cancer","volume":"324","author":"Catalona","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.juro.2013.04.119","article-title":"Early detection of prostate cancer: AUA guideline","volume":"190","author":"Carter","year":"2013","journal-title":"J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.eururo.2025.05.038","article-title":"Magnetic Resonance Imaging-based Biopsy Strategies in Prostate Cancer Screening: A Systematic Review","volume":"88","author":"Schoots","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1001\/jamaoncol.2024.0734","article-title":"Magnetic Resonance Imaging in Prostate Cancer Screening: A Systematic Review and Meta-Analysis","volume":"10","author":"Fazekas","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2329969","DOI":"10.2214\/AJR.23.29969","article-title":"Management of Patients with a Negative Multiparametric Prostate MRI Examination: AJR Expert Panel Narrative Review","volume":"223","author":"Tan","year":"2024","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1001\/jamaoncol.2024.5497","article-title":"Oncological Safety of MRI-Informed Biopsy Decision-Making in Men with Suspected Prostate Cancer","volume":"11","author":"Hamm","year":"2025","journal-title":"JAMA Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Smani, S., Jalfon, M., Sundaresan, V., Lokeshwar, S.D., Nguyen, J., Halstuch, D., Khajir, G., Cavallo, J.A., Sprenkle, P.C., and Leapman, M.S. (2025). Inter-reader reliability and diagnostic accuracy of PI-RADS scoring between academic and community care networks: How wide is the gap?. Urol. Oncol., 43.","DOI":"10.1016\/j.urolonc.2024.10.002"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.euo.2020.02.005","article-title":"Factors Influencing Variability in the Performance of Multiparametric Magnetic Resonance Imaging in Detecting Clinically Significant Prostate Cancer: A Systematic Literature Review","volume":"3","author":"Stabile","year":"2020","journal-title":"Eur. Urol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/pros.24704","article-title":"Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood","volume":"84","author":"Modlin","year":"2024","journal-title":"Prostate"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.eururo.2024.03.027","article-title":"EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent","volume":"86","author":"Cornford","year":"2024","journal-title":"Eur. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e012799","DOI":"10.1136\/bmjopen-2016-012799","article-title":"STARD 2015 guidelines for reporting diagnostic accuracy studies: Explanation and elaboration","volume":"6","author":"Cohen","year":"2016","journal-title":"BMJ Open"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.eururo.2015.06.046","article-title":"A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score","volume":"69","author":"Epstein","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/pros.24858","article-title":"Clinical Sensitivity and Specificity of the PROSTest in an American Cohort","volume":"85","author":"Rahbar","year":"2025","journal-title":"Prostate"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kidd, M., Drozdov, I.A., Matar, S., Gurunlian, N., Ferranti, N.J., Malczewska, A., Bennett, P., Bodei, L., and Modlin, I.M. (2019). Utility of a ready-to-use PCR system for neuroendocrine tumor diagnosis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218592"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102642","DOI":"10.1016\/j.canep.2024.102642","article-title":"Evaluation of a multigenomic liquid biopsy (PROSTest) for prostate cancer detection and follow-up in a Caribbean population","volume":"92","author":"Rosin","year":"2024","journal-title":"Cancer Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"363","DOI":"10.4111\/icu.20230060","article-title":"A prospective study of the prostate health index density and multiparametric magnetic resonance imaging in diagnosing clinically significant prostate cancer","volume":"64","author":"Chen","year":"2023","journal-title":"Investig. Clin. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1177\/20514158211059057","article-title":"Re-evaluating the diagnostic efficacy of PSA as a referral tes to detect clinically significant prostate cancer in contemporary MRI-based image-guided biopsy pathways","volume":"16","author":"Lophatananon","year":"2023","journal-title":"J. Clin. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.21037\/tau.2017.12.31","article-title":"MRI in early prostate cancer detection\u2014How to manage indeterminate or equivocal PI-RADS 3 lesions","volume":"7","author":"Schoots","year":"2018","journal-title":"Transl. Androl. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/bjr\/tqad027","article-title":"Risk stratification of prostate cancer with MRI and prostate-specific antigen density-based tool for personalized decision making","volume":"97","author":"Rajendran","year":"2024","journal-title":"Br. J. Radiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1056\/NEJMoa2100852","article-title":"MRI-Targeted or Standard Biopsy in Prostate Cancer Screening","volume":"385","author":"Eklund","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.cell.2015.10.025","article-title":"The Molecular Taxonomy of Primary Prostate Cancer","volume":"163","author":"Abeshouse","year":"2015","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Johnston, W.L., Catton, C.N., and Swallow, C.J. (2019). Unbiased data mining identifies cell cycle transcripts that predict non-indolent Gleason score 7 prostate cancer. BMC Urol., 19.","DOI":"10.1186\/s12894-018-0433-5"},{"key":"ref_28","unstructured":"Maclin, R., and Opitz, D. (2011, June 01). Popular Ensemble Methods: An Empirical Study. Available online: https:\/\/ui.adsabs.harvard.edu\/abs\/2011arXiv1106.0257M."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eabh2169","DOI":"10.1126\/sciadv.abh2169","article-title":"A single-cell type transcriptomics map of human tissues","volume":"7","author":"Karlsson","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"eGTEx Project (2017). Enhancing GTEx by bridging the gaps between genotype, gene expression, and disease. Nat. Genet., 49, 1664\u20131670.","DOI":"10.1038\/ng.3969"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.eururo.2016.07.008","article-title":"Intratumoral and Intertumoral Genomic Heterogeneity of Multifocal Localized Prostate Cancer Impacts Molecular Classifications and Genomic Prognosticators","volume":"71","author":"Wei","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1158\/1535-7163.MCT-19-0531","article-title":"An Emerging Landscape for Canonical and Actionable Molecular Alterations in Primary and Metastatic Prostate Cancer","volume":"19","author":"Dawson","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/ng.2279","article-title":"Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer","volume":"44","author":"Barbieri","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10822","DOI":"10.3390\/ijms140610822","article-title":"The genomic landscape of prostate cancer","volume":"14","author":"Spans","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/nm.4053","article-title":"Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer","volume":"22","author":"Kumar","year":"2016","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41588-020-00748-0","article-title":"Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction","volume":"53","author":"Conti","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1053\/j.seminoncol.2016.08.001","article-title":"Familial prostate cancer","volume":"43","author":"Giri","year":"2016","journal-title":"Semin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41585-022-00580-7","article-title":"Germline testing and genetic counselling in prostate cancer","volume":"19","author":"Russo","year":"2022","journal-title":"Nat. Rev. Urol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/pros.70086","article-title":"Utility of the PROSTest, a Novel Blood-Based Molecular Assay, Versus PSA for Prostate Cancer Stratification and Detection of Disease","volume":"86","author":"Kidd","year":"2026","journal-title":"Prostate"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rogers, C., Koduru, S.V., Gulati, A., and Halim, A. (2025). PROSTest, a Novel Liquid Biopsy Molecular Assay, Accurately Guides Prostate Cancer Biopsy Decision-Making in Men with Elevated PSA Irrespective of DRE Findings. Cancers, 17.","DOI":"10.3390\/cancers17243908"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/pros.70052","article-title":"PROSTest, a Multigene Liquid Biopsy Signature, Effectively Stratifies Patients With High PSA for Prostate Biopsy","volume":"86","author":"Rahbar","year":"2026","journal-title":"Prostate"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41391-024-00896-y","article-title":"Trends in pre-biopsy MRI usage for prostate cancer detection, 2007\u20132022","volume":"28","author":"Soerensen","year":"2025","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.urolonc.2024.05.012","article-title":"A contemporary review: mpMRI in prostate cancer screening and diagnosis","volume":"43","author":"Launer","year":"2025","journal-title":"Urol. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/s41585-020-0356-2","article-title":"Rethinking prostate cancer screening: Could MRI be an alternative screening test?","volume":"17","author":"Tam","year":"2020","journal-title":"Nat. Rev. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/jmri.70189","article-title":"Artificial Intelligence in Prostate MRI: Addressing Current Limitations Through Emerging Technologies","volume":"63","author":"Johnson","year":"2026","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2530624","DOI":"10.1001\/jamanetworkopen.2025.30624","article-title":"A Payment Incentive to Improve Confirmatory Testing in Men with Prostate Cancer","volume":"8","author":"Srivastava","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jval.2021.07.002","article-title":"Systematic Review of Cost-Effectiveness Models in Prostate Cancer: Exploring New Developments in Testing and Diagnosis","volume":"25","author":"Keeney","year":"2022","journal-title":"Value Health"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/5\/871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T09:00:25Z","timestamp":1773133225000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/5\/871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,8]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cancers18050871"],"URL":"https:\/\/doi.org\/10.3390\/cancers18050871","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,8]]}}}