AR-V7 Expression in Circulating Tumor Cells Predicts Poorer Outcomes in Castration-Resistant Prostate Cancer

Results of a recently published study indicate that presence of circulating tumor cells (CTCs) expressing mRNA for the androgen receptor splice variant 7 (AR-V7) is associated with inferior clinical outcomes in men with castration-resistant prostate cancer (CRPC) receiving treatment with abiraterone or enzalutamide in either the first-line or second-line setting.

The presence of AR-V7 in men with CRPC has previously been shown to correlate with poor outcomes. This prospective analysis examined an expanded cohort of 202 patients with CRPC receiving novel hormonal therapies (95 abiraterone and 107 enzalutamide) to determine how either presence or absence of both CTCs and AR-V7, determined by a CTC-based mRNA assay, corresponded to outcomes, including prostate-specific antigen (PSA) response, PSA progression-free survival (PSA PFS), PFS, and overall survival (OS).

The study identified three prognostic groups on the basis of CTC presence and AR-V7 expression. Patients who were CTC-negative (26.2%) had the best outcomes; patients who were CTC-positive/AR-V7-negative (56%) had intermediate outcomes, and patients who were CTC-positive/AR-V7-positive (17.8%) had the worst outcomes. Patients who were CTC-positive/AR-V7-positive (double positive) were more likely to have Gleason scores ≥8 (P = .05), metastatic disease at diagnosis (P = .01), higher alkaline phosphatase and PSA levels (P<.01), prior abiraterone or enzalutamide use (P = .03), prior taxane use (P = .02), presence of pain (P<.01), and Eastern Cooperative Oncology Group (ECOG) performance status ≥1 (P = .01).

PSA response rates were 75.5% in patients who were CTC-negative, 52.2% in patients who were CTC-positive/AR-V7-negative, and 13.9% in patients who were double-positive. Similar trends were noted for PSA PFS (11.3 months, 6.2 months, 2.1 months) and median PFS (13.9 months, 7.7 months, 3.1 months) across the three biomarker groups. OS was 28.7 months, 29.5 months, and 11.2 months for the CTC-negative, CTC-positive/AR-V7-negative, and double-positive groups respectively. In multivariate analyses, biomarker status was an independent prognostic predictor of PSA response, PSA-PFS, PFS, and OS. Furthermore, biomarker status remained prognostic for all clinical outcomes regardless of whether a patient was receiving first-line or second-line therapy.

The authors concluded that this expanded study supports previous results indicating the prognostic importance of CTC-based AR-V7 in patients with CRPC receiving hormonal therapy with abiraterone or enzalutamide and suggest that this biomarker panel may be useful in the prediction of response to AR-targeted treatments.

J Clin Oncol. 2017 April 6. [Epub ahead of print].


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