Abstract
BACKGROUND: Prostate cancer is the second most common cancer in men. Androgen deprivation therapy (ADT) is the standard treatment, but many patients develop resistance, leading to metastatic castration-resistant prostate cancer (CRPC). Darolutamide, an androgen receptor inhibitor, has shown promise in treating prostate cancer, but its combination with ADT remains under-researched. This study evaluated the safety and efficacy of darolutamide with ADT in patients with hormone-sensitive prostate cancer and CRPC compared to ADT plus placebo. METHODS: We searched electronic databases for randomized controlled trials on darolutamide + ADT in prostate cancer. The primary outcome was overall survival, and secondary outcomes included pain progression, time to subsequent antineoplastic therapy, and adverse events (fatigue, bone fractures, falls, mental disorders, rash, hypertension, and serious events). RESULTS: Four studies (N = 3,473) were included. Darolutamide + ADT showed no significant difference in overall survival (HR = 0.71, P = 0.28), but CRPC patients had improved survival (HR = 1.08, P = 0.007). The combination reduced pain progression [risk ratio (RR) = 0.81, P = 0.001] and delayed subsequent therapy (RR = 0.46, P < 0.00001). Risks of bone fractures (RR = 1.52, P = 0.008) and hypertension (RR = 1.28, P = 0.03) were increased. Other adverse events, such as fatigue, rash, mental disorders, falls, and serious adverse events, showed no significant differences compared to ADT plus placebo. CONCLUSION: Darolutamide + ADT improves outcomes for PC patients but presents safety concerns, including bone fractures and hypertension. Further trials are needed for optimal patient selection and long-term management.