Prostate cancer is the most common cancer among men in Canada. Approximately 1 in 9 Canadian men will be diagnosed with prostate cancer in their lifetime. If prostate cancer is detected early, the survival rate is close to 100%; however, 3 of 4 men will die if the cancer is detected late. The death rate from prostate cancer has dropped by 50% since 1994. In the early development of prostate cancer, cancer cells require androgens to grow; therefore, the cancer at this stage is called (CSPC). Androgen deprivation therapies (ADTs) are treatments that reduce androgen production by the testicles through a surgical procedure or gonadotropin-releasing hormone agonists or antagonists. However, patients treated with an ADT that blocks androgen production eventually become resistant, meaning that the cancer can progress even when the levels of androgens in the body are very low or undetectable. The cancer at this stage is termed (CRPC). Alternative hormone therapies for prostate cancer include treatments that block the action of androgens or their synthesis. Blocking the action of androgens can be achieved by using an androgen receptor blocker, such as enzalutamide (ENZ), apalutamide, or darolutamide, which competes with androgens for binding to androgen receptors, inhibiting the action of androgens in stimulating cancer cell growth. Abiraterone acetate (AA) is an androgen biosynthesis inhibitor that blocks the enzyme CYP17. Both AA and ENZ are androgen receptor–targeted agents (ARTAs). Various treatment options for CRPC include complete blocking of androgen action using ENZ + ADT, complete inhibition of androgen production using AA and ADT, immunotherapy using a cell-based immunotherapy named Sipuleucel-T, chemotherapy using taxanes such as docetaxel (DTX) or cabazitaxel (CTX), radiopharmaceutical radium-223, and sequential therapies among ARTAs and taxanes. A recent CADTH report identified weak evidence on 4 sets of comparative sequences of ARTA in the treatment of patients with metastatic CRPC. These were ENZ-to-ENZ + AA versus ENZ-to-AA, AA-to-ENZ versus ENZ-to-AA, ARTA-to-ARTA versus ARTA-to-taxane (DTX or CTX), and ARTA-to-ARTA versus ARTA-to-taxane-to-ARTA. It was found that AA had modest benefit in patients with metastatic CRPC (mCRPC) who progressed after treatment with ENZ, and the combination of ENZ + AA given as second-line therapy was not indicated because of observed adverse effects. The AA-to-ENZ sequence provided better clinical outcomes than the ENZ-to-AA sequence in mCRPC patients. After ARTA therapy, patients with mCRPC who received second-line taxane therapy achieved higher response rates compared with second-line ARTA. There was no difference in efficacy between ARTA-to-ARTA and ARTA-to-taxane-to-ARTA. No comparative cost-effectiveness studies were identified in the previous CADTH report. The aim of this report is to update and extend the previous report by reviewing the comparative clinical effectiveness and cost-effectiveness of varying treatment sequences of ARTA in patients with prostate cancer, including CSPC and CRPC with or without metastasis.