Associations between AR-V7 status in circulating tumour cells, circulating tumour cell count and survival in men with metastatic castration-resistant prostate cancer

• Published in: European journal of cancer (1990) 2019-11, Vol.121, p.48-54
• Main Authors: Belderbos, Bodine P.S., Sieuwerts, Anieta M., Hoop, Esther Oomen-de, Mostert, Bianca, Kraan, Jaco, Hamberg, Paul, Van, Mai N., Beaufort, Corine M., Onstenk, Wendy, van Soest, Robert J., Martens, John, Sleijfer, Stefan, de Wit, Ronald, Mathijssen, Ron H.J., Lolkema, Martijn P.
• Format: Article
• Language: English
• Subjects: AR-V7; Biomarker; Biomarkers; Castration; Cell survival; Circulating tumour cells; Clinical trials; Confidence intervals; Medical prognosis; Metastases; Metastasis; Metastatic castration-resistant prostate cancer; Patients; Prognosis; Prostate cancer; Subgroups; Survival; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2019.08.005

The interpretation of the presence of AR-V7 in circulating tumour cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) remains to be elucidated. AR-V7 may hold promise as a predictive biomarker, but there may be prognostic impact of AR-V7 positivity as well. To investigate the clinical value of AR-V7, we determined whether AR-V7 detection in CTCs in patients with mCRPC is associated with CTC counts and survival. Between December 2011 and January 2019, three prospective clinical trials collected clinical data of patients with mCRPC, who progressed after docetaxel and/or enzalutamide or abiraterone. Baseline (and follow-up) blood samples were withdrawn determining CTC count and AR-V7 expression. The majority of patients started cabazitaxel as the next line of treatment after AR-V7 characterisation. A total of 127 samples were evaluable for the analysis of CTC count versus AR-V7 status. Although an association was observed between AR-V7 and CTC count in all patients with mCRPC (p = 0.017), no such association was found in the prognostic unfavourable subgroup of patients with ≥5 CTCs. After adjusting for clinical prognostic factors, AR-V7 expression in CTCs was not associated with overall survival (hazard ratio = 1.33, 95% confidence interval = 0.81–2.15, p = 0.25). We found that AR-V7 expression in CTCs had no additional prognostic value in patients with mCRPC, mostly treated with cabazitaxel. In patients with mCRPC with a predefined worse prognosis of a higher CTC count (≥5), a predictive biomarker is an important unmet medical need. Prospective trials should investigate whether AR-V7 detection in CTCs may guide treatment selection for these adverse prognosis patients. •AR-V7 in circulating tumor cells had no additional prognostic value in mCRPC patients.•A predictive biomarker is an important unmet need in prostate cancer treatment.•Prospective trials should investigate if AR-V7 detection may guide treatment selection.