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

Cancer Biol Med. 2024 Dec 24;21(11):1012-1032. doi: 10.20892/j.issn.2095-3941.2024.0139.

Abstract

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.

Keywords: Luteinizing hormone-releasing hormone receptor agonists; long-term survival; luteinizing hormone-releasing hormone receptor antagonists; next-generation hormonal agents; prostate cancer.

Publication types

  • Review

MeSH terms

  • Androstenes
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Gonadotropin-Releasing Hormone / agonists
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Humans
  • Male
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / mortality
  • Prostatic Neoplasms* / pathology
  • Receptors, LHRH* / agonists
  • Receptors, LHRH* / antagonists & inhibitors

Substances

  • Receptors, LHRH
  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone
  • abiraterone
  • Androstenes