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dc.date.accessioned2018-03-21T08:33:02Z
dc.date.available2018-03-21T08:33:02Z
dc.date.created2017-12-03T12:45:36Z
dc.date.issued2017
dc.identifier.citationWalker, Steven M. Knight, Laura A. McCavigan, Andrena M. Logan, Gemma E. Berge, Viktor Sherif, Amir Pandha, Hardev Warren, Anne Y. Davidson, Catherine Uprichard, Adam Blayney, Jaine K. Price, Bethanie Jellema, Gera L. Steele, Christopher J. Svindland, Aud McDade, Simon S. Eden, Christopher G. Foster, Chris Mills, Ian Geoffrey Neal, David E. Mason, Malcolm D. Kay, Elaine W. Waugh, David J. Harkin, D. Paul Watson, R. William Clarke, Noel W. Kennedy, Richard D. . Molecular subgroup of primary prostate cancer presenting with metastatic biology. European Urology. 2017, 72(4), 509-518
dc.identifier.urihttp://hdl.handle.net/10852/61198
dc.description.abstractBackground Approximately 4–25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. Objective To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Design, setting, and participants Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Outcome measurements and statistical analysis Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. Results and limitations A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13–2.33]; p = 0.0092) and metastatic recurrence (multivariable HR = 3.20 [1.76–5.80]; p = 0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR = 2.67 [1.90–3.75]; p < 0.0001 and HR = 7.53 [4.13–13.73]; p < 0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. Conclusions The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. Patient summary The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.en_US
dc.languageEN
dc.language.isoenen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleMolecular subgroup of primary prostate cancer presenting with metastatic biologyen_US
dc.typeJournal articleen_US
dc.creator.authorWalker, Steven M.
dc.creator.authorKnight, Laura A.
dc.creator.authorMcCavigan, Andrena M.
dc.creator.authorLogan, Gemma E.
dc.creator.authorBerge, Viktor
dc.creator.authorSherif, Amir
dc.creator.authorPandha, Hardev
dc.creator.authorWarren, Anne Y.
dc.creator.authorDavidson, Catherine
dc.creator.authorUprichard, Adam
dc.creator.authorBlayney, Jaine K.
dc.creator.authorPrice, Bethanie
dc.creator.authorJellema, Gera L.
dc.creator.authorSteele, Christopher J.
dc.creator.authorSvindland, Aud
dc.creator.authorMcDade, Simon S.
dc.creator.authorEden, Christopher G.
dc.creator.authorFoster, Chris
dc.creator.authorMills, Ian Geoffrey
dc.creator.authorNeal, David E.
dc.creator.authorMason, Malcolm D.
dc.creator.authorKay, Elaine W.
dc.creator.authorWaugh, David J.
dc.creator.authorHarkin, D. Paul
dc.creator.authorWatson, R. William
dc.creator.authorClarke, Noel W.
dc.creator.authorKennedy, Richard D.
cristin.unitcode185,57,11,0
cristin.unitnameMills/Engedal Group - Prostate Cancer
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.fulltextpostprint
cristin.qualitycode2
dc.identifier.cristin1522032
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=European Urology&rft.volume=72&rft.spage=509&rft.date=2017
dc.identifier.jtitleEuropean Urology
dc.identifier.volume72
dc.identifier.issue4
dc.identifier.startpage509
dc.identifier.endpage518
dc.identifier.doihttp://dx.doi.org/10.1016/j.eururo.2017.03.027
dc.identifier.urnURN:NBN:no-63819
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn0302-2838
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/61198/2/Walker%2Bet%2Bal%2BEuropean%2BUrology%2B2017.pdf
dc.type.versionPublishedVersion
dc.relation.projectNFR/144182


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