2021 CUA-CUOG CRPC guideline summary
Castration-resistant prostate cancer (CRPC) includes a wide range of disease types: from patients without metastases or symptoms with rising prostate-specific antigen (PSA) levels despite androgen deprivation therapy (ADT) to patients with metastases and significant debilitation due to cancer symptoms.
Androgen deprivation therapy  Because androgen receptor remains active in most patients who have developed castration-resistant disease, it is recommended that ADT be continued for the remainder of a patient’s life (Strong recommendation).
I. Rising PSA non-metastatic CRPC ADT should be maintained in the nmCRPC state (Level 3, Strong recommendation). First-generation androgen receptor antagonists (i.e., bicalutamide, flutamide, etc.) should be discontinued if patients are receiving these agents (Level 3, Weak recommendation). Men with high-risk nmCRPC, defined as a PSADT <10 months, with an estimated life expectancy of greater than five years should be offered apalutamide, enzalutamide, or darolutamide (Level 1, Strong recommendation). In men with high-risk nmCRPC who are felt to be unsuitable or refuse approved therapies, observation or use of first-generation androgen receptor antagonists may be attempted (Level 3, Weak recommendation). Men with nmCRPC who are not considered high-risk, observation or secondary hormonal treatments may be attempted (Level 3, Weak recommendation). Patients who are untreated for nmCRPC should be followed with regular imaging every 6–12 months depending on PSA doubling time (PSADT) (Level 3, Weak recommendation).
II. Chemotherapy-naive metastatic CRPC (mCRPC) without symptoms or minimally symptomatic Abiraterone acetate 1000 mg/day plus prednisone 5 mg/twice daily is recommended as first-line therapy (Level 1, Strong recommendation). Enzalutamide 160 mg/day is recommended as first-line therapy (Level 1, Strong recommendation). Docetaxel 75 mg/m2 every three weeks plus 5 mg oral prednisone twice daily can be offered (Level 1, Strong recommendation). The timing of docetaxel therapy in men with evidence of metastases but without symptoms should be discussed with the patient and therapy should be individualized based on the patient’s clinical status and preference.
III. mCRPC with moderate or severe symptoms Docetaxel 75 mg/m2 every three weeks plus 5 mg oral prednisone twice daily is recommended (Level 1, Strong recommendation). Radium-223 every four weeks for six cycles is recommended in patients with pain due to bone metastases and who do not have visceral metastases (Level 1, Strong recommendation). Radium-223 significantly improved overall survival and reduced symptomatic skeletal-related events in patients with symptomatic mCRPC who had previously received docetaxel chemotherapy or were deemed unfit for docetaxel. Abiraterone acetate 1000 mg/day plus prednisone 5 mg twice daily or enzalutamide 160 mg/day may be considered as first-line therapy in patients who cannot receive or refuse docetaxel (Expert opinion).
IV. mCRPC who progress after docetaxel-based chemotherapy  Options with survival benefit Cabazitaxel (25 mg/m2) plus prednisone (5 mg/day) (Level 1, Strong recommendation). Radium-223 every four weeks for six cycles (Level 1, Strong recommendation). If not received prior to docetaxel: Abiraterone acetate (1000 mg per day) plus prednisone (5 mg twice daily) (Level 1, Strong recommendation) Enzalutamide (160 mg/day) (Level 1, Strong recommendation)  Options with unknown survival benefit Docetaxel plus prednisone re-exposure in patients who have had a previous favorable response to docetaxel may be reasonable (Expert opinion). Mitoxantrone plus prednisone may be offered for palliative pain relief (Expert opinion, Weak recommendation).
V. Patients with CRPC and bone metastases (includes the pre- or post-chemotherapy settings) Denosumab (120 mg subcutaneous) or zoledronic acid (4 mg intravenous) every four weeks, along with daily calcium and vitamin D supplementation is recommended to prevent disease-related skeletal complications (Level 1, Strong recommendation).
VI. Patients with mCPRC and HRR mutation who have progressed on a previous ARAT with or without taxane exposure Olaparib 300 mg BID