For advanced or metastatic cancer, once LHRH agonist therapy is initiated for life, systemic therapy with newer anti-androgen pathway inhibitors and chemotherapy, typically docetaxel, is recommended.

However, chemotherapy may not always be used due to the circumstances of their cancer (eg low volume disease), or concerns about quality of life or how much extended lifespan is likely.⁴³

Anti-androgen tablets include abiraterone (taken with prednisolone), darolutamide, or enzalutamide. Enzalutamide, a potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway, can induce cell death and tumour regression. Apalutamide may be used where the cancer has stopped responding to other hormone therapy.^41,44

Barrier contraception is advised for men on anti-androgens having intercourse with women of child-bearing potential.⁴¹

Hormone-relapsed (also known as hormone-resistant, hormone-refractory and castrate-resistant) PC refers to the typically eventual failure of primary androgen deprivation therapy. Docetaxel may suit patients not too reliant on care for daily living. Dexamethasone may also be considered as a third-line hormonal therapy.³⁴