While there have been important developments for patients with metastatic castration-resistant prostate cancer (CRPC), many patients will not have metastatic disease (M0) when castration resistance develops, says Charles J. Ryan, MD. Non-metastatic CRPC is often detected biochemically, through a rise in PSA levels in men who are currently taking androgen deprivation therapy. It remains unknown how to optimally treat this population, notes Ryan, as the standards of care for metastatic disease do not apply to these individuals.
A nonrandomized phase II study evaluating prostate-specific androgen (PSA) changes in 125 individuals treated with abiraterone acetate and low-dose prednisone is ongoing. A 50% decline in PSA was demonstrated in 87% of patients who had received abiraterone. However, this small study will likely not alter treatment standards in individuals with non-metastatic CRPC, comments Ryan.
ARN-509 is a novel androgen receptor antagonist similar to enzalutamide but with less CNS penetration, potentially resulting in reduced levels of fatigue and seizures. A randomized phase III study is assessing ARN-509 in men with non-metastatic CRPC. If this study demonstrates efficacy in delaying metastases and the need for opiates, it has the potential to become the new standard of care in this setting, says Ryan.
Galeterone, another investigational antiandrogen, shares similar properties with abiraterone and enzalutamide and appears to lower androgen production. It may also have activity against tumors with the AR-V7 variant, explains Ryan, which renders abiraterone and enzalutamide ineffective.