Clinical Utility of CTC AR-V7 Status in mCRPC

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TAKE-HOME MESSAGE

•This is a retrospective analysis of circulating tumor cell (CTC) androgen receptor variant-7 (AR-V7) and the association with matched tumor biopsy AR-V7 and clinical outcomes of 181 patients with metastatic castration-resistant prostate cancer. CTC/AR-V7+ was detected in approximately one-third of patients. Of note, tissue AR-V7+ was detected in both CTC− (63%) and CTC+/AR-V7− patients (63% and 62%, respectively), and no difference in survival was found between these two groups.

•This is an interesting and original study, as it is one of the few studies reporting on the concordance of AR-V7 status between liquid and tumor biopsies in mCRPC.

– Pedro C. Barata, MD

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.

European Urology Focus

Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-Resistant Prostate Cancer

Eur Urol Focus 2019 Apr 27;[EPub Ahead of Print], A Sharp, JC Welti, MBK Lambros, D Dolling, DN Rodrigues, L Pope, C Aversa, I Figueiredo, J Fraser, Z Ahmad, C Lu, P Rescigno, M Kolinsky, C Bertan, G Seed, R Riisnaes, S Miranda, M Crespo, R Pereira, A Ferreira, G Fowler, B Ebbs, P Flohr, A Neeb, D Bianchini, A Petremolo, S Sumanasuriya, A Paschalis, J Mateo, N Tunariu, W Yuan, S Carreira, SR Plymate, J Luo, JS de Bono