High-risk nonmetastatic castration-resistant prostate cancer is a lethal disease 
that previously lacked clear treatment options. Progression to bone metastases 
is associated with significant morbidity and high cost. Apalutamide, an androgen 
receptor inhibitor, has substantial clinical response in nonmetastatic 
castration-resistant prostate cancer. Apalutamide + androgen deprivation therapy 
is well tolerated and improves metastasis-free survival, progression-free 
survival and time to symptomatic progression, and is associated with a favorable 
trend of improved overall survival. Future research is needed to elucidate 
mechanisms of resistance to treatment with androgen signaling inhibitors.