Introduction
Metastatic castration-resistant prostate cancer (mCRPC) remains a formidable clinical challenge and a leading cause of cancer mortality among men globally. Despite advances in systemic therapies such as androgen receptor pathway inhibitors (ARPIs) including enzalutamide and abiraterone, survival outcomes remain suboptimal, particularly when bone metastases are present. Radium-223 dichloride (Ra223), an alpha particle-emitting radiopharmaceutical that selectively targets osteoblastic bone metastases, has previously demonstrated survival benefit when used as monotherapy in symptomatic mCRPC patients. However, combination strategies with ARPIs have encountered safety concerns as noted in the ERA 223 trial where Ra223 was combined with abiraterone, leading to increased fracture rates and mortality. The EORTC 1333/PEACE-3 trial investigates the combination of enzalutamide with Ra223 as first-line therapy in mCRPC with bone metastases, with enforced use of bone-protecting agents (BPAs) to mitigate skeletal adverse events.
