{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T20:12:47Z","timestamp":1773173567094,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"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: Elevated PSAs combined with an abnormal digital rectal examination (DRE) are strong indicators of the possibility of a prostate cancer (PCa) and are used to guide biopsy decisions. We evaluated whether PROSTest, a novel, clinically validated, blood-based multigene mRNA test could aid in biopsy decision-making irrespective of DRE results in subjects \u226545 years with PSA \u2265 3 ng\/mL. Methods: A retrospective cohort analysis was performed with a prespecified statistical analysis plan to test the null hypothesis that an abnormal DRE does not materially affect the sensitivity, specificity, or overall stratification performance of PROSTest. The pool included 327 subjects aged \u226545 years with abnormal PSA (\u22653 ng\/mL) who had undergone DRE and prostate biopsy. Diagnostic performance of PROSTest (measured pre-biopsy) was evaluated within two PSA strata (3\u201310 ng\/mL and &gt;10 ng\/mL) and compared to DRE in the same strata. Metrics including sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. Results: Among 327 subjects, 215 had PSA 3\u201310 ng\/mL and 112 had PSA &gt; 10 ng\/mL. A total of 131 cancers (40.1%) were diagnosed. PROSTest achieved high sensitivity (93.9\u201396.6%), specificity (82.4\u201392.7%), and overall accuracy (up to 94.1%) across all DRE\/PSA combinations. The DRE+\/PROSTest+ group demonstrated similarly high sensitivity (96.6%) and specificity (92.7%), comparable to the DRE\u2212\/PROSTest+ group. Multivariate analysis confirmed PROSTest as an independent predictor of PCa (OR: 154, p &lt; 0.0001), outperforming DRE. Conclusions: PROSTest provides highly accurate risk stratification in men with elevated PSA, independent of DRE findings and may be used with PSA to much more effectively guide biopsy decisions.<\/jats:p>","DOI":"10.3390\/cancers17243908","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:17:36Z","timestamp":1765185456000},"page":"3908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PROSTest, a Novel Liquid Biopsy Molecular Assay, Accurately Guides Prostate Cancer Biopsy Decision-Making in Men with Elevated PSA Irrespective of DRE Findings"],"prefix":"10.3390","volume":"17","author":[{"given":"Craig G.","family":"Rogers","sequence":"first","affiliation":[{"name":"Vattikuti Urology Institute, Henry Ford Health, Detroit, MI 48202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-2908","authenticated-orcid":false,"given":"Srinivas V.","family":"Koduru","sequence":"additional","affiliation":[{"name":"Wren Laboratories, Branford, CT 06405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Gulati","sequence":"additional","affiliation":[{"name":"Bennett Cancer Center, Stamford, CT 06902, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdel B.","family":"Halim","sequence":"additional","affiliation":[{"name":"Wren Laboratories, Branford, CT 06405, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/S0140-6736(24)00651-2","article-title":"The Lancet Commission on prostate cancer: Planning for the surge in cases","volume":"403","author":"James","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.eururo.2019.08.005","article-title":"Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates","volume":"77","author":"Culp","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.eururo.2023.04.021","article-title":"2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review","volume":"84","author":"Bergengren","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_4","unstructured":"American Cancer Society (2024). Key Statistics for Prostate Cancer, American Cancer Society."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1056\/NEJM198710083171501","article-title":"Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate","volume":"317","author":"Stamey","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/(SICI)1097-0045(1996)7+<3::AID-PROS1>3.0.CO;2-T","article-title":"Discordance of assay methods creates pitfalls for the interpretation of prostate-specific antigen values","volume":"7","author":"Semjonow","year":"1996","journal-title":"Prostate Suppl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1056\/NEJMoa031918","article-title":"Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter","volume":"350","author":"Thompson","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.urology.2010.11.056","article-title":"Barriers and facilitators to digital rectal examination screening among African-American and African-Caribbean men","volume":"77","author":"Lee","year":"2011","journal-title":"Urology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1158\/1055-9965.EPI-05-0019","article-title":"Prostate cancer screening behavior in men from seven ethnic groups: The fear factor","volume":"15","author":"Consedine","year":"2006","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1136\/bmj.39493.646875.AE","article-title":"Going from evidence to recommendations","volume":"336","author":"Guyatt","year":"2008","journal-title":"BMJ (Clin. Res. Ed.)"},{"key":"ref_11","unstructured":"NCCN (2025). NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection, NCCN. [2.2025 ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S0022-5347(01)61785-3","article-title":"Digital rectal examination for detecting prostate cancer at prostate specific antigen levels of 4 ng\/mL. or less","volume":"161","author":"Carvalhal","year":"1999","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.eururo.2008.03.104","article-title":"The role of the digital rectal examination in subsequent screening visits in the European randomized study of screening for prostate cancer (ERSPC), Rotterdam","volume":"54","author":"Gosselaar","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.urology.2007.07.019","article-title":"Characteristics of prostate cancer detected by digital rectal examination only","volume":"70","author":"Okotie","year":"2007","journal-title":"Urology"},{"key":"ref_15","first-page":"E453","article-title":"Utility of digital rectal examination in a population with prostate cancer treated with active surveillance","volume":"14","author":"Wettstein","year":"2020","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/pros.24203","article-title":"The prognostic value of digital rectal exam for the existence of advanced pathologic features after prostatectomy","volume":"81","author":"Prebay","year":"2021","journal-title":"Prostate"},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cca.2014.06.019","article-title":"The influence of prostate volume in prostate health index performance in patients with total PSA lower than 10 \u03bcg\/L","volume":"436","author":"Filella","year":"2014","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.juro.2010.12.032","article-title":"A multicenter study of [-2]pro-prostate specific antigen combined with prostate specific antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng\/ml prostate specific antigen range","volume":"185","author":"Catalona","year":"2011","journal-title":"J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/S0022-5347(05)64263-2","article-title":"Discrimination of benign from malignant prostatic disease by selective measurements of single chain, intact free prostate specific antigen","volume":"168","author":"Steuber","year":"2002","journal-title":"J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5534\/wjmh.230386","article-title":"Liquid Biomarkers in Prostate Cancer Diagnosis: Current Status and Emerging Prospects","volume":"43","author":"Liu","year":"2025","journal-title":"World J. Men\u2019s Health"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","unstructured":"Kidd, M., Rempega, G., Kepinski, M., Slomian, S., Mlynarek, K., and Halim, A.B. (2025). Utility of the PROSTest, a Novel Blood-Based Molecular Assay, Versus PSA for Prostate Cancer Stratification and Detection of Disease. Prostate, online ahead of print.","DOI":"10.1002\/pros.70086"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"140","DOI":"10.6004\/jnccn.2024.0019","article-title":"NCCN Guidelines\u00ae Insights: Prostate Cancer, Version 3.2024","volume":"22","author":"Schaeffer","year":"2024","journal-title":"J. Natl. Compr. Cancer Netw. JNCCN"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"236","DOI":"10.6004\/jnccn.2023.0014","article-title":"NCCN Guidelines\u00ae Insights: Prostate Cancer Early Detection, Version 1.2023","volume":"21","author":"Moses","year":"2023","journal-title":"J. Natl. Compr. Cancer Netw. JNCCN"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.med.53.082901.104000","article-title":"Early management of prostate cancer: How to respond to an elevated PSA?","volume":"53","author":"Canto","year":"2002","journal-title":"Annu. Rev. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1177\/1557988307312784","article-title":"Prostate cancer screening in African American men: Barriers and methods for improvement","volume":"2","author":"Reynolds","year":"2008","journal-title":"Am. J. Men\u2019s Health"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E301","DOI":"10.5489\/cuaj.8710","article-title":"Screening guidelines for individuals at increased risk for prostate cancer","volume":"18","author":"Lorentz","year":"2024","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.euo.2023.12.005","article-title":"Comparing the Performance of Digital Rectal Examination and Prostate-specific Antigen as a Screening Test for Prostate Cancer: A Systematic Review and Meta-analysis","volume":"7","author":"Matsukawa","year":"2024","journal-title":"Eur. Urol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1370\/afm.2205","article-title":"Digital Rectal Examination for Prostate Cancer Screening in Primary Care: A Systematic Review and Meta-Analysis","volume":"16","author":"Naji","year":"2018","journal-title":"Ann. Fam. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/24\/3908\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:22:19Z","timestamp":1765185739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/24\/3908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,6]]},"references-count":31,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["cancers17243908"],"URL":"https:\/\/doi.org\/10.3390\/cancers17243908","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,6]]}}}