Abiraterone and enzalutamide represent the standard treatment in castration resistance prostate cancer (CRPC) patients, however, some patient displays primary resistance, and several studies investigated the role of the androgen receptor (AR) as a predictive biomarker of response to treatment (Conteduca, et al. Ann Oncol. 2017;28(7):1508-1516; Del Re, et al. BJU Int. 2019 doi: 10.1111/bju.14792). The present study is aimed at evaluating the role the AR in liquid biopsy to predict response to hormone treatment in CRPC patients.
Six ml of plasma samples were collected from patients affected by castration-resistant prostate cancer before the beginning of first-line hormonal treatment. Circulating free DNA and exosome-RNA were isolated for analysis of AR-gain and AR-V7 by digital droplet PCR.
Eighty-four CRPC were prospectively enrolled in this study. 40 patients received abiraterone and 44 patients received enzalutamide as first-line hormonal therapy. AR-gain was detected in 12 patients (14.3%) and 36% were AR-V7+ at baseline. Median PFS and OS were significantly longer in AR-V7- vs AR-V7+ patients (24.3 vs 5.4 months, p < 0.0001; not reached vs 16.2 months, p < 0.0001, respectively). Patients carrying of the AR-gain had a median PFS of 4.8 vs 24.3 months of non-gained AR patients (P < 0.0001). Median OS was significantly longer in AR-no gain vs AR-gain (not reached vs 8.17 months, p < 0.0001). A significant correlation between AR-V7 and AR-gain was observed (r = 0.28; p = 0.01). In the univariate model, known risk factors for progression such as AR-V7, AR-gain, neutrophil/lymphocyte ratio and metastatic spread to either bone or lymph nodes were analysed. In multivariable analysis, only AR-V7 and AR gain were confirmed as independent predictive biomarkers (p < 0.0001 and p = 0.004, respectively).
The present study demonstrates that cfDNA and exosomal RNA are a reliable source of AR-variants and their detection predicts resistance to anti-hormonal therapy. The method is sensitive, fast and represents a convenient alternative to other potentially more expensive and less sensitive approaches.
The authors.
Has not received any funding.
V. Conteduca: Travel/Accommodation/Expenses: Janssen; Travel/Accommodation/Expenses: Astellas; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Bayer. U.F.F. De Giorgi: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Sanofi; Advisory/Consultancy: Astellas; Advisory/Consultancy: Byer; Advisory/Consultancy: BMS; Honoraria (self): Ipsen; Advisory/Consultancy: Janssen; Advisory/Consultancy: Merk; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Travel/Accommodation/Expenses: BMS; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Janssen; Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.