BERKELEY, CA (UroToday.com) - Lower urinary tract symptoms (LUTS) are common in elderly men with benign prostatic conditions or prostate cancer (PCa) and frequently lead to them seeking medical care.[1] Consequently, LUTS are often present at the time of prostate cancer diagnosis and can have a considerable impact on patients’ quality of life and general well-being, especially when severe.[2, 3]
GnRH agonists (plus antiandrogen flare protection) are a standard treatment for patients with PCa suffering LUTS. However, the mechanism of action of GnRH agonists results in an initial surge in testosterone levels, which can stimulate tumour growth and exacerbate clinical symptoms (‘clinical flare’).[4] In contrast to GnRH agonists, GnRH antagonists immediately block the GnRH receptor, resulting in fast suppression of testosterone levels, without a surge.[4] This study (NCT00831233; CS28) was the first to assess the efficacy and tolerability of the GnRH antagonist, degarelix, compared with a standard treatment (goserelin + bicalutamide; G+B) in the relief of LUTS secondary to PCa.
The trial was stopped early due to the low recruitment rate and this led to a reduced sample size. In total 40 patients received treatment (27 with degarelix and 13 with G+B); most had locally advanced disease and were highly symptomatic.
- Degarelix was non-inferior to G+B in reducing International Prostate Symptom Score (IPSS) at week 12 in the full analysis set (p=0.20)
- The significantly larger IPSS reduction in the per-protocol analysis (p=0.04) was suggestive of a superior reduction with degarelix.
- Significantly more degarelix patients had improved quality of life at week 12 (85% vs 46%; p=0.01).
- Mean prostate size reductions at week 12 were 42% versus 25% for patients receiving degarelix versus G+B, respectively (p=0.04).
Most of the patients randomised in this study had advanced and highly symptomatic disease, which reflects the original stringent recruitment criteria. However, because the effect of degarelix on IPSS, reduction was greater than expected; it was still possible to show that this agent was non-inferior to G+B at reducing IPSS at week 12 in the full analysis set, despite the reduced sample size.
Interestingly, two further 3-month studies have been published recently which assess the benefit of degarelix compared with G+B in the relief of LUTS. Mason and colleagues[5] investigated neoadjuvant hormone treatment in patients scheduled to undergo radical radiotherapy and Axcrona et al.[6] considered reductions in LUTS and total prostate volume (TPV) in patients in need of androgen deprivation therapy but not considered for radiotherapy. Both these studies revealed that degarelix is non-inferior to G+B in terms of TPV reduction. Furthermore, treatment with degarelix offered a greater reduction in IPSS and improved LUTS relief compared with G+B.
The results of these three studies, while not directly comparable due to the different patient populations recruited, demonstrate that degarelix provides at least similar TPV reduction to goserelin plus antiandrogen flare protection and also a consistent advantage in terms of IPSS reduction and the relief of LUTS.
References:
- Bright E, Abrams P. Diseases of the prostate. Rev Clin Gerontol 2010; 20: 10–19.
- Gammack JK. Lower urinary tract symptoms. Clin Geriatr Med 2010; 26: 249–260.
- Batista-Miranda JE Molinuevo B, Pardo Y. Impact of lower urinary tract symptoms on quality of life using Functional Assessment Cancer Therapy scale. Urology 2007; 69: 285–288.
- Van Poppel H, Nilsson S. Testosterone surge: rationale for gonadotropin-releasing hormone blockers? Urology 2008; 71: 1001–1006.
- Mason M, Maldonado Pijoan X, Steidle C, Guerif S, Wiegel T, van der Meulen E, Bergqvist PB, Khoo V. Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide. Clinical Oncology 2013; 25: 190–196.
- Axcrona K, Aaltomaa S, da Silva CM, Ozen H, Damber JE, Tankó LB, Colli E, Klarskov P. Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide. BJU Int. 2012; 110: 1721–1728.
Written by:
Bo-Eric Persson, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
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