dc.contributor.author | Sharp, A | |
dc.contributor.author | Welti, JC | |
dc.contributor.author | Lambros, MBK | |
dc.contributor.author | Dolling, D | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Pope, L | |
dc.contributor.author | Aversa, C | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Fraser, J | |
dc.contributor.author | Ahmad, Z | |
dc.contributor.author | Lu, C | |
dc.contributor.author | Rescigno, P | |
dc.contributor.author | Kolinsky, M | |
dc.contributor.author | Bertan, C | |
dc.contributor.author | Seed, G | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Miranda, S | |
dc.contributor.author | Crespo, M | |
dc.contributor.author | Pereira, R | |
dc.contributor.author | Ferreira, A | |
dc.contributor.author | Fowler, G | |
dc.contributor.author | Ebbs, B | |
dc.contributor.author | Flohr, P | |
dc.contributor.author | Neeb, A | |
dc.contributor.author | Bianchini, D | |
dc.contributor.author | Petremolo, A | |
dc.contributor.author | Sumanasuriya, S | |
dc.contributor.author | Paschalis, A | |
dc.contributor.author | Mateo, J | |
dc.contributor.author | Tunariu, N | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Plymate, SR | |
dc.contributor.author | Luo, J | |
dc.contributor.author | de Bono, JS | |
dc.date.accessioned | 2019-07-17T09:50:48Z | |
dc.date.issued | 2019-11-01 | |
dc.identifier.citation | European urology, 2019, 76 (5), pp. 676 - 685 | |
dc.identifier.issn | 0302-2838 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3300 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.doi | 10.1016/j.eururo.2019.04.006 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 676 - 685 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Protein Isoforms | |
dc.subject | Receptors, Androgen | |
dc.subject | Biopsy | |
dc.subject | Neoplasm Staging | |
dc.subject | Prognosis | |
dc.subject | Cell Count | |
dc.subject | Reproducibility of Results | |
dc.subject | Genetic Techniques | |
dc.subject | Alternative Splicing | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.subject | Neoplastic Cells, Circulating | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.title | Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-04-09 | |
rioxxterms.versionofrecord | 10.1016/j.eururo.2019.04.006 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | European urology | |
pubs.issue | 5 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 76 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
icr.researchteam | Translational Therapeutics | |
dc.contributor.icrauthor | Sharp, Adam | |
dc.contributor.icrauthor | Rescigno, Pasquale | |
dc.contributor.icrauthor | Seed, George | |
dc.contributor.icrauthor | Miranda, Susana | |
dc.contributor.icrauthor | Pereira, Ana Rita | |
dc.contributor.icrauthor | Sumanasuriya, Semini | |
dc.contributor.icrauthor | Paschalis, Alec | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | De Bono, Johann | |