Androgen Receptor Directed Therapy on Cognitive Function in Patients Treated With Darolutamide or Enzalutamide

Open to males ages 18 years and up

include:

- Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features - Progressive disease per PCWG3 criteria - Metastatic CRPC or non-metastatic CRPC (M0CRPC) - Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA >2 ng/mL. - For mCRPC: metastatic disease documented by standard or novel imaging techniques

OR for M0CPRC: no evidence of metastatic disease on standard imaging.

- Surgically or medically castrated, with testosterone levels of <50 ng/dL. If the patient is medically castrated, continuous dosing with GnRHa must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study. - Eastern Cooperative Oncology Group (ECOG) performance status ≤2 - Able to complete cognitive testing and patient reported outcome surveys in English. - Ability to swallow study tablets whole. - Able to provide informed consent.

include:

- Prior chemotherapy for treatment of CRPC. Patients who received chemotherapy for castrate-sensitive prostate cancer are still eligible provided chemotherapy was completed >6 months prior to study entry. - Use of investigational agents for the treatment of prostate cancer within 4 weeks of study entry. - Prior usage of ENZ or DARO. - Prior use of apalutamide - Prior use of investigational agents that act on the androgen axis. - Progression during treatment with abiraterone (PSA or radiographic progression). Must have < 12 weeks of abiraterone exposure prior to enrollment if given for treatment of CRPC. If used with radiation for high risk localized hormone sensitive disease, can enroll if no progression of disease during treatment with abiraterone (PSA or radiographic) and >6 months since last exposure to abiraterone. - Planned radiation treatment > 21 days during enrollment in the study. - Any active, or prior history of, brain metastasis that have not been treated and stabilized. - Active or history of seizures or seizure disorder. - Prior diagnosis of dementia or other neurologic impairment. - Use of chronic opiates (other than stable doses of opioids that in the view of the patient and investigator do not affect cognition). - Clinically significant history of falls or risk of falls at baseline (timed up-and-go (TUG) test time of >12 seconds).