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Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer

Abstract

The androgen receptor splice variant AR-V7 has recently been discussed as a predictive biomarker for nonresponse to next-generation androgen deprivation therapy (ADT) in patients with castration-resistant prostate cancer. However, we recently identified one patient showing a response from abiraterone despite expression of AR-V7 in his circulating tumour cells (CTC).

Therefore, we precisely assessed the response in a cohort of 21 AR-V7 positive castration-resistant prostate cancer patients who had received therapy with abiraterone or enzalutamide. We detected a subgroup of six AR-V7 positive patients showing benefit from either abiraterone or enzalutamide. Their progression free survival was 26 d (censored) to 188 d. Four patients displayed a prostate-specific antigen decrease of >50%. When analysing prior therapies, we noticed that only one of the six patients had received next-generation ADT prior to CTC collection.

As a result, we conclude that AR-V7 status in CTC cannot entirely predict nonresponse to next generation ADT and AR-V7-positive patients should not be systematically denied abiraterone or enzalutamide treatment, especially as effective alternative treatment options are still limited.

Patient summary

A subgroup of patients can benefit from abiraterone and/or enzalutamide despite detection of AR-V7 splice variants in their circulating tumour cells.

Take Home Message

Androgen receptor splice variant-7 expression in circulating tumour cells from patients with castration-resistant prostate cancer cannot entirely predict nonresponse to next-generation androgen deprivation therapy. Therefore, androgen receptor splice variant-7-positive patients should not be denied abiraterone or enzalutamide treatment systematically, especially as effective alternative treatment options are still limited.

Keywords: Abiraterone, Enzalutamide, Androgen receptor splice variant, AR-V7, Castration resistant prostate cancer.

Footnotes

a Clinic of Urology, University Hospital Muenster, Muenster, Germany

b Clinic of Urology, University Hospital Ulm, Ulm, Germany

c Gerhard-Domagk-Institute of Pathology, University Hospital Muenster, Muenster, Germany

Corresponding author. Department of Urology, Muenster University Medical Centre, Albert-Schweitzer-Campus 1, Building A 1, Muenster D-48149, Germany. Tel. +49 (0) 2 51/83-44609; Fax: +49 (0) 2 51/83-44619.