Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer.
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Authors
Sharp, A
Welti, JC
Lambros, MBK
Dolling, D
Rodrigues, DN
Pope, L
Aversa, C
Figueiredo, I
Fraser, J
Ahmad, Z
Lu, C
Rescigno, P
Kolinsky, M
Bertan, C
Seed, G
Riisnaes, R
Miranda, S
Crespo, M
Pereira, R
Ferreira, A
Fowler, G
Ebbs, B
Flohr, P
Neeb, A
Bianchini, D
Petremolo, A
Sumanasuriya, S
Paschalis, A
Mateo, J
Tunariu, N
Yuan, W
Carreira, S
Plymate, SR
Luo, J
de Bono, JS
Welti, JC
Lambros, MBK
Dolling, D
Rodrigues, DN
Pope, L
Aversa, C
Figueiredo, I
Fraser, J
Ahmad, Z
Lu, C
Rescigno, P
Kolinsky, M
Bertan, C
Seed, G
Riisnaes, R
Miranda, S
Crespo, M
Pereira, R
Ferreira, A
Fowler, G
Ebbs, B
Flohr, P
Neeb, A
Bianchini, D
Petremolo, A
Sumanasuriya, S
Paschalis, A
Mateo, J
Tunariu, N
Yuan, W
Carreira, S
Plymate, SR
Luo, J
de Bono, JS
Document Type
Journal Article
Date
2019-11-01
Date Accepted
2019-04-09
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.
Citation
European urology, 2019, 76 (5), pp. 676 - 685
Source Title
Publisher
ELSEVIER
ISSN
0302-2838
eISSN
1873-7560
Collections
Research Team
Cancer Biomarkers
Prostate Cancer Targeted Therapy Group
Translational Therapeutics
Prostate Cancer Targeted Therapy Group
Translational Therapeutics