Recent reports have emphasized the clinical relevance of detecting the androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs). Our aim was to set up a validated multicenter pipeline to measure AR-V7 by RT-qPCR in RNA isolated from CellSearch-enriched CTCs to provide an AR-V7 positive/negative score in a clinically acceptable time range. CellSearch-enirched CTCs from metastatic castration-resistant prostate cancer patients were characterized by RT-qPCR. After optimization it was prospectively tested whether it was possible to report the AR-V7 status within 11 days (PRELUDE study). In the range of the RNA equivalent of 0.2 to 12 VCaP cells the coefficient of variation for AR-V7 was 9% (n = 37). The LOD was 0.3 and the LOQ 3 cells in the final RT-qPCR. No differences were observed between AR-V7 data generated by four technicians or in two different laboratories. For the 45 patients in the PRELUDE study, 13 patients were ineligible, 22 patients were AR-V7 negative, and 10 AR-V7 positive. The median time to inform the physician of the test result was 7 (2 to 11) days. THIS assay CAN establish the AR-V7 status in CTCs from metastatic castration-resistant prostate cancer patients. Furthermore, it was possible to provide an AR-V7 outcome within 11 days, indicating that it may be used to choose between an anti-AR or taxane-based cabazitaxel treatment.
The Journal of molecular diagnostics : JMD. 2018 Feb 20 [Epub ahead of print]
Anieta M Sieuwerts, Bianca Mostert, Michelle van der Vlugt-Daane, Jaco Kraan, Corine Beaufort, Mai Van, Wendy J C Prager, Bram De Laere, Nick Beije, Paul Hamberg, Hans M Westgeest, Metin Tascilar, Luc Y Dirix, Wendy Onstenk, Ronald de Wit, Martijn P Lolkema, Ron H J Mathijssen, John W M Martens, Stefan Sleijfer
Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Rotterdam, The Netherlands. Electronic address: ., Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Rotterdam, The Netherlands., GZA Hospitals Sint-Augustinus, Wilrijk, Belgium & Center for Oncological Research, University of Antwerp, Antwerp, Belgium., Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands., Department of Internal Medicine, Amphia Ziekenhuis, Breda, The Netherlands., Department of Internal Medicine, Isala Ziekenhuis, Zwolle, The Netherlands.