GnRH blockers: a changing paradigm in the management of prostate cancer

Abstract

For more than 60 years, androgen deprivation therapy, first with orchidectomy and more recently with gonadotrophin‐releasing hormone (GnRH) agonists, has been a key treatment approach in the management of advanced prostate cancer. In spite of showing comparable survival benefits, these two treatments are associated with both physical and psychological issues, with notable effects on patient quality of life. The development of GnRH blockers provides a new class of hormonal agent with a different, direct mode of action. Degarelix, a newly approved GnRH blocker, has displayed a fast, profound and sustained suppression of testosterone and prostate‐specific antigen levels without subsequent tumour flare effects. This paper considers the current evidence for this new treatment approach and how this may impact on current urology nursing practice.

The role of gonadotrophin-releasing hormone antagonists in the treatment of patients with advanced hormone-dependent prostate cancer in the UK

“…The overall aim of ADT in advanced PC is to reduce testosterone levels, thereby minimising an important stimulus to androgen-sensitive PC cells and causing them to undergo apoptosis [3, 4]. ADT delays disease progression [5] and can also result in the dramatic reduction of skeletal metastases, decreased post-void residual urine and improved quality of life (QoL) [6].…”

“…The GnRH agonists currently available share broadly similar overall survival outcomes [3] and achieve similar clinical improvements, such as reductions in bone pain, spinal cord compression risk and ureteral obstruction in the longer term [7]. Typically, GnRH agonists are indicated for the treatment of locally advanced/metastatic PC, as well as neo-adjuvant or adjuvant use with radiotherapy in high-risk localised or locally advanced PC [8].…”

“…Testosterone suppression is only achieved after an initial LH surge that not only delays the testosterone reaching castrate levels, but also stimulates overproduction of testosterone for the first 30 days [9]. This potentially results in transient tumour expansion and a resultant flare in clinical symptoms, including worsened bone pain, urinary obstruction, spinal cord compression and potential CV effects [3, 9, 10]. Additionally, 5–17 % of men do not achieve acceptable testosterone suppression of ≤50 ng/dL [11], and 13–34 % do not achieve the more widely accepted modern threshold of 20 ng/dL [12–14].…”

“…Given that PC patients tend to be aged 65 years or older and that agonist-based ADT is associated with osteopenia and increased fracture risk [3], it may be appropriate to offer bone densitometry testing using dual energy X-ray absorptiometry (DEXA). Blood tests may also be appropriate to diagnose diabetes mellitus and metabolic syndrome.…”

“…The irreversibility of the surgical procedure, along with its understandable lack of popularity with patients and clinicians, has led to increased use of chemical castration, with GnRH agonists being introduced in the 1980s, followed by GnRH antagonists in 2003 [3]. …”