Androgen Deprivation Therapy

For place in therapy, please refer to the relevant section of the SACT pathway.

This page details choice of ADT only.

Options for Androgen Deprivation Therapy (ADT) include Luteinising Hormone Releasing Hormone (LHRH) agonists and antagonists.

The choice of therapy is determined by local formularies and availability of products, patients' clinical circumstances and preferences, and tolerability of side effects.

Clinicians should refer to the SmPC when choosing an LHRH analogue.

LHRH Agonists

In most cases, an LHRH agonist would be considered the preferred choice of ADT, with a short period of bicalutamide cover for tumour flare prevention.

Examples of LHRH agonists include leuprorelin, goserelin, histrelin and triptorelin.

Some considerations when choosing a LHRH agonist are:

Inclusion on local formulary
Frequency and route of injection

LHRH antagonists

Use of an LHRH antagonist at the initiation of ADT (instead of an LHRH agonist) may be considered in the following circumstances:

Patients in whom 'tumour flare' associated with other LHRH analogues would be problematic, including:
- Actual or imminent spinal cord compression whilst non-castrate.
- Clinically significant ureteric obstruction whilst non-castrate (ie. causing hydronephrosis and impaired renal function).
Patients with high risk of a cardiovascular (CV) event occurring (defined as those with a history of : stroke, TIA, MI, intervention for coronary disease (eg stent, coronary artery bypass graft (CABG)), abdominal aortic aneurysm and peripheral vascular disease)*.

Examples of LHRH antagonists include degarelix (S/C monthly injection) and relugolix (oral daily dose).

Other factors such as route and frequency of administration and anticipated patient compliance should also be considered when choosing the most appropriate treatment for a patient. Local formulary should be consulted for indications and conditions of use of a particular LHRH antagonist before prescribing.

*Androgen deprivation therapy is associated with increased risk of cardiovascular morbidity and mortality. In an unplanned retrospective combined analysis of 6 randomised trials comparing the LHRH antagonist degarelix with LHRH agonist, patients who had experienced a previous major cardiovascular event (MACE; stroke, myocardial infarction, coronary artery intervention) on degarelix had a significantly lower incidence of subsequent cardiovascular event when compared to the patients receiving the agonist (Albertsen et al. Eur Urol. 2014 Mar;65(3):565-73). A prospective trial addressing this question with degarelix failed to accrue adequate numbers, but a prospectively-planned safety analysis within the pivotal randomised trial comparing relugolix with LHRH agonist confirmed the finding (Shore et al. N Engl J Med 2020;382:2187-2196). Therefore, in patients with a prior history of MACE, consider using LHRH antagonist (degarelix or relugolix). The relative risk of cardiovascular toxicity should be considered alongside other factors such as route of administration and anticipated compliance when choosing the most appropriate method of castration for each individual patient.

References:

Leuprorelin and goserelin pre-date SMC - refer to SmPC.

Histrelin SMC557/09