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.
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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.
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.
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2016 Aug 03 [Epub ahead of print]
Fangfang Qu, Wanling Xie, Mari Nakabayashi, Haitao Zhang, Seong Ho Jeong, Xiaodong Wang, Kazumasa Komura, Christopher J Sweeney, Oliver Sartor, Gwo-Shu Mary Lee, Philip W Kantoff
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School., Biostatistics and Computational Biology, Dana-Farber Cancer Institute., Department of Medical Oncology, Dana-Farber Cancer Institute., Pathology and Laboratory Medicine, Tulane University School of Medicine., Medical Oncology, Dana Farber Cancer Institute., Department of Medical Oncology, Dana-Farber Cancer Institute., Medical Oncology, Dana Farber Cancer Institute., Medical Oncology, Dana-Farber Cancer Institute., Medicine and Urology, Tulane University School of Medicine., Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School., Department of Medicine, Memorial Sloan Kettering Cancer Center .