Androgen Receptor Splice Variant 7 Predicts Shorter Response in Patients with Metastatic Hormone-sensitive Prostate Cancer Receiving Androgen Deprivation Therapy

Abstract

BackgroundWhether AR-V7 expression can predict the response in patients with metastatic hormone-sensitive prostate cancer (mHSPC) who receive androgen deprivation therapy (ADT) remains to be explored. ObjectiveTo evaluate the predictive value of AR-V7 expression in the prognosis of mHSPC patients receiving ADT. Design, setting, and participantsIn this multicenter prospective cohort study, 310 mHSPC patients commencing ADT were enrolled. Standard immunohistochemical staining was used to assess AR-V7 protein expression in biopsy tissues collected before initiation of ADT. Outcome measurements and statistical analysisKaplan-Meier survival estimates and Cox regression analyses were used to evaluate associations of AR-V7 status (positive vs negative) with progression-free survival (PFS) and overall survival (OS). Results and limitationsSixty-four (21%) patients were AR-V7–positive and 246 (79%) patients were AR-V7–negative. The median follow-up for patients not confirmed dead was 25 mo (interquartile range 10–30). Compared to AR-V7-negative patients, AR-V7-positive patients had significantly shorter PFS (hazard ratio [HR] 47.39, 95% confidence interval [CI] 25.83–86.94) and OS (HR 3.57, 95% CI 1.46–8.72). In multivariable analysis, AR-V7 was an independent predictive factor (HR 7.61, 95% CI 5.24–11.06) for shorter PFS. Limitations include the sample size and follow-up period. ConclusionsAR-V7 expression in primary cancer tissue is correlated with poor prognosis for mHSPC patients receiving ADT. Patient summaryIn this study of men with metastatic hormone-sensitive prostate cancer, AR-V7 protein expression in primary cancer tissue was associated with poor outcomes on androgen deprivation therapy.