ABSTRACT: Purpose: We evaluated the association of prostate specific antigen (PSA) and androgen receptor splice variant-7 (AR-V7) transcript levels in patients’ blood with time to treatment failure (TTF) and overall survival (OS) with abiraterone acetate (AA) and/or enzalutamide treatment in castration resistant prostate cancer (CRPC) patients. Experimental design: RNA levels of AR-V7 and PSA in peripheral blood collected before treatment were quantified using Droplet Digital-PCR in retrospective cohorts treated with AA (N=81) or enzalutamide (N=51) for CRPC. Multivariable Cox regression adjusted for known prognostic factors was used for analyses. Results: PSA-transcripts were detected in 57% of AA-treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients (adjusted-HR=2.27 (95%CI: 1.26, 4.10) and 2.60 (95%CI: 1.19, 5.69); p-value=0.006 and 0.017 in AA and enzalutamide cohorts, respectively). Patients with a higher-AR-V7 transcript level had a shorter TTF with AA and enzalutamide in univariate analysis (median 8.0 versus 15.6 months, p=0.046 in AA-cohort and 3.6 versus 5.6 months, p=0.050 in enzalutamide-cohort). In multivariable models, the association with TTF remained significant in the enzalutamide-cohort (adjusted-HR=2.02; 95%CI:1.01, 4.05; p=0.048), but statistically insignificant in the AA-cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS. Conclusions: PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with AA or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells.