Evan Y. Yu, MD, discusses how the PEACE-3 study data may be practice-changing in specific scenarios for androgen receptor pathway inhibitor (ARPI)–naive metastatic castration-resistant prostate cancer (mCRPC), particularly in patients who have not received prior androgen receptor pathway inhibitors (ARPIs) or abiraterone (ABI), considering how the findings may influence treatment decisions in light of the current landscape. He also addresses how the combination of enzalutamide (ENZA) and radium-223 (Ra-223) could be considered in the management of symptomatic mCRPC, while discussing the caveats of the ALSYMPCA study, particularly its conduct in an era prior to the introduction of ABI and ENZA. Additionally, he explores the role of bone-protecting agents and the importance of bone density scans for patients receiving an ARPI and Ra-223 in combination.