Luteinizing hormone-releasing hormone receptor agonists and antagonists in prostate cancer: effects on long-term survival and combined therapy with next-generation hormonal agents

Prostate cancer is a leading cause of cancer-related death in men worldwide. Luteinizing hormone-releasing hormone receptor (LHRH-R) agonists and antagonists are known to achieve castration-level testosterone suppression; however, long-term data comparing the survival benefits of these therapies are insufficient to inform treatment decisions. Furthermore, the advent of next-generation hormonal agents (NHAs), such as abiraterone and enzalutamide, have shifted the paradigm of managing prostate cancer. Although LHRH-R agonists and antagonists remain the cornerstone treatment across various stages of prostate cancer, they are increasingly administered with NHAs, because the combination treatment confers a survival advantage. Nevertheless, the differences in efficacy and safety profiles among various combinations of LHRH-R agonists and antagonists and NHAs remain unclear. Hence, this narrative review is aimed at providing a comprehensive overview of the long-term outcomes of various LHRH-R agonists and antagonists. Key data from major clinical studies are summarized, categorized by disease stage. LHRH-R agonists and antagonists, particularly goserelin, have demonstrated long-term survival benefits in patients with localized and locally advanced prostate cancer. The clinical outcomes of different LHRH-R agonists and antagonists in combination with NHAs have also been evaluated. Among the various combinations, goserelin plus abiraterone appears to have a manageable safety profile with relatively low rates of hot flushes and fatigue. Overall, long-term survival data and safety profiles should be considered in selecting optimal combination therapies for prostate cancer treatment.