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dc.contributor.authorCreed, Jenniferen
dc.contributor.authorKlotz, Laurenceen
dc.contributor.authorHarbottle, Andrewen
dc.contributor.authorMaggrah, Andreaen
dc.contributor.authorReguly, Brianen
dc.contributor.authorGeorge, Anneen
dc.contributor.authorGnanapragasm, Vincenten
dc.date.accessioned2018-03-23T11:11:56Z
dc.date.available2018-03-23T11:11:56Z
dc.date.issued2018-03en
dc.identifier.issn0724-4983
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274267
dc.description.abstractPURPOSE: To determine the clinical performance of a blood-based test for clinically significant (CS) prostate cancer (PCa) (grade group ≥ 2) intended for use in men with prostate serum antigen levels in the 'grey zone' (PSA < 10 ng/ml). The test quantifies a previously described 3.4 kb mitochondrial DNA (mtDNA) deletion. METHODS: In a first prospective study of an MRI-guided re-biopsy population (n = 126), the 3.4 kb deletion and 18S rRNA gene were amplified from plasma. A diagnostic threshold was selected from the coordinates of the receiver operating characteristic curve and tested in a second population of men who were (n = 92) biopsy naïve when the mtDNA deletion was assayed and for whom those diagnosed with cancer on initial biopsy were treated with radical prostatectomy. RESULTS: The 3.4 kb deletion was a good predictor of CS PCa in the image-guided re-biopsy population [AUC 0.84, (95% CI 0.73-0.95)] and the selected threshold corresponded to a sensitivity of 87% [95% CI, 70-96%], specificity of 68% [95% CI, 47-85%] and negative predictive value (NPV) of 97%. Applying this threshold to the second population showed this deletion to be a strong predictor of CS cancer [AUC 0.98, (95% CI 0.94-1.02)], independent of PSA or age [sensitivity 100% (95% CI, 93-100%), specificity 90% (95%CI 73-98%) and NPV 100%]. CONCLUSION: The 3.4 kb deletion in plasma is an accurate predictor of CS cancer for men in the PSA 'grey zone'. Used in advance of biopsy for improved patient selection, this deletion may reduce the number of biopsies needed to diagnose CS prostate cancers.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSpringer
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectProstateen
dc.subjectHumansen
dc.subjectProstatic Neoplasmsen
dc.subjectKallikreinsen
dc.subjectProstate-Specific Antigenen
dc.subjectDNA, Mitochondrialen
dc.subjectRNA, Ribosomal, 18Sen
dc.subjectBiopsyen
dc.subjectProstatectomyen
dc.subjectSensitivity and Specificityen
dc.subjectROC Curveen
dc.subjectSequence Deletionen
dc.subjectBase Sequenceen
dc.subjectAgeden
dc.subjectMiddle Ageden
dc.subjectMaleen
dc.subjectImage-Guided Biopsyen
dc.titleA single mitochondrial DNA deletion accurately detects significant prostate cancer in men in the PSA 'grey zone'.en
dc.typeArticle
prism.endingPage348
prism.issueIdentifier3en
prism.publicationDate2018en
prism.publicationNameWorld journal of urologyen
prism.startingPage341
prism.volume36en
dc.identifier.doi10.17863/CAM.21388
dcterms.dateAccepted2017-12-07en
rioxxterms.versionofrecord10.1007/s00345-017-2152-zen
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-03en
dc.identifier.eissn1433-8726
rioxxterms.typeJournal Article/Reviewen


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International