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dc.contributor.authorSharp, A
dc.contributor.authorWelti, JC
dc.contributor.authorLambros, MBK
dc.contributor.authorDolling, D
dc.contributor.authorRodrigues, DN
dc.contributor.authorPope, L
dc.contributor.authorAversa, C
dc.contributor.authorFigueiredo, I
dc.contributor.authorFraser, J
dc.contributor.authorAhmad, Z
dc.contributor.authorLu, C
dc.contributor.authorRescigno, P
dc.contributor.authorKolinsky, M
dc.contributor.authorBertan, C
dc.contributor.authorSeed, G
dc.contributor.authorRiisnaes, R
dc.contributor.authorMiranda, S
dc.contributor.authorCrespo, M
dc.contributor.authorPereira, R
dc.contributor.authorFerreira, A
dc.contributor.authorFowler, G
dc.contributor.authorEbbs, B
dc.contributor.authorFlohr, P
dc.contributor.authorNeeb, A
dc.contributor.authorBianchini, D
dc.contributor.authorPetremolo, A
dc.contributor.authorSumanasuriya, S
dc.contributor.authorPaschalis, A
dc.contributor.authorMateo, J
dc.contributor.authorTunariu, N
dc.contributor.authorYuan, W
dc.contributor.authorCarreira, S
dc.contributor.authorPlymate, SR
dc.contributor.authorLuo, J
dc.contributor.authorde Bono, JS
dc.date.accessioned2019-07-17T09:50:48Z
dc.date.issued2019-11-01
dc.identifier.citationEuropean urology, 2019, 76 (5), pp. 676 - 685
dc.identifier.issn0302-2838
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3300
dc.identifier.eissn1873-7560
dc.identifier.doi10.1016/j.eururo.2019.04.006
dc.description.abstractBACKGROUND: Detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumour cells (CTCs) is associated with worse outcome in metastatic castration-resistant prostate cancer (mCRPC). However, studies rarely report comparisons with CTC counts and biopsy AR-V7 protein expression. OBJECTIVE: To determine the reproducibility of AdnaTest CTC AR-V7 testing, and associations with clinical characteristics, CellSearch CTC counts, tumour biopsy AR-V7 protein expression and overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: CTC AR-V7 status was determined for 227 peripheral blood samples, from 181 mCRPC patients with CTC counts (202 samples; 136 patients) and matched mCRPC biopsies (65 samples; 58 patients). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: CTC AR-V7 status was associated with clinical characteristics, CTC counts, and tissue biopsy AR-V7 protein expression. The association of CTC AR-V7 status and other baseline variables with OS was determined. RESULTS AND LIMITATIONS: Of the samples, 35% were CTC+/AR-V7+. CTC+/AR-V7+ samples had higher CellSearch CTC counts (median CTC; interquartile range [IQR]: 60, 19-184 vs 9, 2-64; Mann-Whitney test p<0.001) and biopsy AR-V7 protein expression (median H-score, IQR: 100, 63-148 vs 15, 0-113; Mann-Whitney test p=0.004) than CTC+/AR-V7- samples. However, both CTC- (63%) and CTC+/AR-V7- (62%) patients had detectable AR-V7 protein in contemporaneous biopsies. After accounting for baseline characteristics, there was shorter OS in CTC+/AR-V7+ patients than in CTC- patients (hazard ratio [HR] 2.13; 95% confidence interval [CI] 1.23-3.71; p=0.02); surprisingly, there was no evidence that CTC+/AR-V7+ patients had worse OS than CTC+/AR-V7- patients (HR 1.26; 95% CI 0.73-2.17; p=0.4). A limitation of this study was the heterogeneity of treatment received. CONCLUSIONS: Studies reporting the prognostic relevance of CTC AR-V7 status must account for CTC counts. Discordant CTC AR-V7 results and AR-V7 protein expression in matched, same-patient biopsies are reported. PATIENT SUMMARY: Liquid biopsies that determine circulating tumour cell androgen receptor splice variant-7 status have the potential to impact treatment decisions in metastatic castration-resistant prostate cancer patients. Robust clinical qualification of these assays is required before their routine use.
dc.formatPrint-Electronic
dc.format.extent676 - 685
dc.languageeng
dc.language.isoeng
dc.publisherELSEVIER
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectNeoplasm Metastasis
dc.subjectProtein Isoforms
dc.subjectReceptors, Androgen
dc.subjectBiopsy
dc.subjectNeoplasm Staging
dc.subjectPrognosis
dc.subjectCell Count
dc.subjectReproducibility of Results
dc.subjectGenetic Techniques
dc.subjectAlternative Splicing
dc.subjectDrug Resistance, Neoplasm
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectNeoplastic Cells, Circulating
dc.subjectProstatic Neoplasms, Castration-Resistant
dc.titleClinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer.
dc.typeJournal Article
dcterms.dateAccepted2019-04-09
rioxxterms.versionofrecord10.1016/j.eururo.2019.04.006
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean urology
pubs.issue5
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume76
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkers
icr.researchteamProstate Cancer Targeted Therapy Group
icr.researchteamTranslational Therapeutics
dc.contributor.icrauthorSharp, Adam
dc.contributor.icrauthorRescigno, Pasquale
dc.contributor.icrauthorSeed, George
dc.contributor.icrauthorMiranda, Susana
dc.contributor.icrauthorPereira, Ana Rita
dc.contributor.icrauthorSumanasuriya, Semini
dc.contributor.icrauthorPaschalis, Alec
dc.contributor.icrauthorCarreira, Suzanne
dc.contributor.icrauthorDe Bono, Johann


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