Factors that guide selection among androgen receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer

Prostate cancer is the most common cancer affecting men in the United States. A significant proportion of men have nonmetastatic castration-resistant prostate cancer (CRPC), in which biochemical progression is evidenced by rising levels of prostate-specific antigen without radiographic progression in the setting of castrate levels of testosterone. Historically, the preferred treatment for these patients has been observation and continued treatment with androgen deprivation therapy (ADT). The standard of care has recently evolved to include the addition of androgen receptor (AR) inhibitors to ADT. The US Food and Drug Administration has approved 3 next-generation AR inhibitors for nonmetastatic CRPC: apalutamide, enzalutamide, and darolutamide. These agents were approved based on data from phase 3 randomized trials. There is now a significant amount of data from these trials. All 3 agents improve metastasis-free survival and overall survival. Selection of treatment can be guided by factors such as the patient's overall health and frailty, potential drug-drug interactions, and the safety profile associated with each agent.