Clinical Utility of the Nuclear-localized AR-V7 Biomarker in Circulating Tumor Cells in Improving Physician Treatment Choice in Castration-resistant Prostate Cancer

Abstract

Background-Proof of the clinical utility of a biomarker is when its use informs a management decision and improves patient outcomes relative to when it is not.Objective-To model the clinical benefit of the nuclear-localized AR-V7 test for men with progressing metastatic castration-resistant prostate cancer (mCRPC) at the second line of therapy or greater to inform the choice of an androgen receptor signaling inhibitor (ARSI) or a taxane. Design, setting, and participants-The study population was a cross-sectional cohort of 193 unique patients with progressing mCRPC from whom 255 samples were drawn at the time of the second line or later treatment decision who received an ARSI or taxane, with up to 3 yr of additional follow-up. Physicians were blinded to AR-V7 status and the testing laboratory was blinded to outcomes.Outcome measurements and statistical analyses-We measured physician propensity for choosing an ARSI or taxane based on patient prognosis, as well as overall survival (OS) adjusted for physician propensity by drug class without or with knowledge of nuclear localized AR-V7 status in circulating tumor cells (CTCs).

The Prognostic Value of Androgen Receptor Splice Variant 7 in Castration-Resistant Prostate Cancer Treated With Novel Hormonal Therapy or Chemotherapy: A Systematic Review and Meta-analysis

“…A report by Graf et al indicated that doctors prefer taxane to NHT for patients with a highly aggressive disease or who have received NHT previously, which might result in treatment selection tendency. After adjusting physician propensity, no marked differences in OS were observed between taxane-and NHT-treated patients (42). Elsewhere, nuclear CTC expression of AR-V7 protein was associated with better survival in mCRPC patients receiving taxane therapy than those receiving NHT (11).…”

Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer

“…In the context of clinical studies, patients with CTCs expressing AR-V7 showed worst outcome when compared to those patients harboring AR-V7-negative CTCs or no CTCs (52). Very recently, it was demonstrated that men with metastatic PCA who were tested positive for nuclear-localized AR-V7 protein in CTCs were likely to live longer if taxane based chemotherapy was used (53). In the PROPHECY Trial, a multicenter, prospective-blinded study of men with high-risk metastatic castration resistant PCA starting abiraterone acetate or enzalutamide treatment, the detection of AR-V7 in CTCs by two assays was independently associated with shorter PFS and OS, concluding that such men should be offered alternative treatments (54).…”

Prostate cancer androgen receptor splice variant 7 biomarker study - a multicentre randomised feasibility trial of biomarker-guided personalised treatment in patients with advanced prostate cancer (the VARIANT trial) study protocol

“…Poorer failure free survival (but not overall survival was additionally seen in men with worse primary tumour stage and higher PSA level before starting ADT. There is overlap between these poor prognostic features and factors associated with a high likelihood of harbouring AR-V7 positive CTCs 33 40 51…”