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Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer.
Sharp, Adam; Welti, Jon C; Lambros, Maryou B K; Dolling, David; Rodrigues, Daniel Nava; Pope, Lorna; Aversa, Caterina; Figueiredo, Ines; Fraser, Jennifer; Ahmad, Zai; Lu, Changxue; Rescigno, Pasquale; Kolinsky, Michael; Bertan, Claudia; Seed, George; Riisnaes, Ruth; Miranda, Susana; Crespo, Mateus; Pereira, Rita; Ferreira, Ana; Fowler, Gemma; Ebbs, Berni; Flohr, Penny; Neeb, Antje; Bianchini, Diletta; Petremolo, Antonella; Sumanasuriya, Semini; Paschalis, Alec; Mateo, Joaquin; Tunariu, Nina; Yuan, Wei; Carreira, Suzanne; Plymate, Stephen R; Luo, Jun; de Bono, Johann S.
Afiliación
  • Sharp A; The Institute for Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK.
  • Welti JC; The Institute for Cancer Research, London, UK.
  • Lambros MBK; The Institute for Cancer Research, London, UK.
  • Dolling D; The Institute for Cancer Research, London, UK.
  • Rodrigues DN; The Institute for Cancer Research, London, UK.
  • Pope L; The Institute for Cancer Research, London, UK.
  • Aversa C; The Royal Marsden NHS Foundation Trust, London, UK.
  • Figueiredo I; The Institute for Cancer Research, London, UK.
  • Fraser J; The Institute for Cancer Research, London, UK.
  • Ahmad Z; The Institute for Cancer Research, London, UK.
  • Lu C; Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Rescigno P; The Institute for Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK; University of Naples Federico II, Naples, Italy.
  • Kolinsky M; University of Alberta, Edmonton, Alberta, Canada.
  • Bertan C; The Institute for Cancer Research, London, UK.
  • Seed G; The Institute for Cancer Research, London, UK.
  • Riisnaes R; The Institute for Cancer Research, London, UK.
  • Miranda S; The Institute for Cancer Research, London, UK.
  • Crespo M; The Institute for Cancer Research, London, UK.
  • Pereira R; The Institute for Cancer Research, London, UK.
  • Ferreira A; The Institute for Cancer Research, London, UK.
  • Fowler G; The Institute for Cancer Research, London, UK.
  • Ebbs B; The Institute for Cancer Research, London, UK.
  • Flohr P; The Institute for Cancer Research, London, UK.
  • Neeb A; The Institute for Cancer Research, London, UK.
  • Bianchini D; The Royal Marsden NHS Foundation Trust, London, UK.
  • Petremolo A; The Royal Marsden NHS Foundation Trust, London, UK.
  • Sumanasuriya S; The Institute for Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK.
  • Paschalis A; The Institute for Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK.
  • Mateo J; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • Tunariu N; The Royal Marsden NHS Foundation Trust, London, UK.
  • Yuan W; The Institute for Cancer Research, London, UK.
  • Carreira S; The Institute for Cancer Research, London, UK.
  • Plymate SR; University of Washington and VAPSHCS GRECC, Seattle, WA, USA.
  • Luo J; Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • de Bono JS; The Institute for Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK. Electronic address: Johann.de-Bono@icr.ac.uk.
Eur Urol ; 76(5): 676-685, 2019 11.
Article en En | MEDLINE | ID: mdl-31036442
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Androgénicos / Neoplasias de la Próstata Resistentes a la Castración / Células Neoplásicas Circulantes Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans / Male / Middle aged Idioma: En Revista: Eur Urol Año: 2019 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Androgénicos / Neoplasias de la Próstata Resistentes a la Castración / Células Neoplásicas Circulantes Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans / Male / Middle aged Idioma: En Revista: Eur Urol Año: 2019 Tipo del documento: Article País de afiliación: Reino Unido