What alternative therapies would you consider for a patient with metastatic castration-sensitive prostate cancer who declines GnRH analogues?

This situation is fairly uncommon, particularly in the metastatic setting, where these therapies are nearly universally effective and toxicities generally manageable. The alternatives of bicalutamide at high dose (150 mg/d) and enzalutamide also have toxicities and much less evidence to support their use as an alternative to ADT.  Orchiectomy is reasonable for men with injection phobias and who will need long term continuous ADT.  Most men today with mHSPC are receiving more intensive ADT with GnRH agonists/antagonists and abiraterone acetate/prednisone based on the LATTITUTE and STAMPEDE trials.  Generally, this involves sitting down with patients and having a goals of care discussion and supporting them through the hot flashes, fatigue, muscle loss and weight gain with pro-active counseling, exercise and diet, and supportive care medications as needed.