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AUA 2018

AUA 2018: Superior Efficacy of Degarelix as Neoadjuvant Hormone Therapy in Control of Acute Genitourinary Toxicity Associated with Radiation Therapy for Prostate Cancer

San Francisco, CA (UroToday.com) Degarelix, sold under the brand name Firmagon, is a GnRH antagonist that competes with the natural GnRH decapeptide for binding to GnRH receptors in the pituitary gland. Results of a systematic review and meta-analysis found that degarelix offers superior control of lower urinary tract symptoms compared to luteinizing hormone-releasing hormone (LHRH) agonists, such as leuprolide [1]. However, whether degarelix can reduce acute genitourinary toxicity associated with radiation therapy when used as a neoadjuvant ADT agent remains unclear. As such, Junpei Iizuka, MD, from Tokyo, Japan and colleagues discussed results of a propensity-score matched analysis comparing degarelix and LHRH agonist. The aim of their study was to evaluate the efficacy of degarelix as neoadjuvant ADT followed by radiation therapy in the control of acute genitourinary toxicity compared to LHRH agonist.

The authors identified 355 patients between May 2005 and May 2014 who had received neoadjuvant ADT for intermediate- to high-risk prostate cancer followed by intensity-modulated radiation therapy (IMRT). Among these patients, 25 (7%) were treated with degarelix and 330 with an LHRH agonist. Both groups received neoadjuvant ADT in combination with antiandrogen agents for 6 months. Propensity-score matching was performed using clinical variables, which included: 

  • Age
  • PSA level
  • Clinical stage
  • Biopsy Gleason score
  • D′Amico risk stratification
  • Prostate volume
  • History of diabetes mellitus
  • Pre-treatment use of alpha-1 blockers
  • Radiation dose per fraction (2 or 3 Gy/fraction)
  • Pre-treatment frequency of nocturnal urination
Genitourinary toxicity was estimated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 guidelines and acute toxicity was defined as any toxicity developing within 3 months after the end of radiation therapy.
Comparing the two groups, patients receiving degarelix more commonly had T2 disease and less commonly T1 disease compared to patients receiving LHRH agonists (p=0.02), in addition to more commonly receiving 2Gy fractions than 3Gy fractions of IMRT (p=0.03). Propensity-score matching resulted in 23 patients in each group, and the matched cohort showed no significant differences in clinical variables between groups. In the matched cohort, acute genitourinary toxicity was detected at a significantly lower rate in the degarelix group than in the LHRH agonist group (39.1% vs 69.6%, p=0.038). Furthermore, post-treatment frequency of nocturnal urination was also significantly lower in the degarelix group than in the LHRH agonist group (2.21±0.27 vs. 3.34±0.27, p=0.005). 

The strength of the current study is that this is the first study assessing the ability of two different ADT agents to decrease genitourinary toxicity in patients receiving IMRT for localized prostate cancer. A limitation of the study is the small sample of men receiving degarelix, which affected the size of the matched comparison group to only 23 patients per group. Based on the results of their findings, Iizuka concluded that degarelix may reduce acute genitourinary toxicity associated with IMRT compared to LHRH agonist, and may be useful as neoadjuvant ADT followed by irradiation. Indeed, these results will need to be validated in larger cohorts, if not in future prospective trials.


References:

1. Cui Y, Zong H, Yan H, et al. Degarelix versus goserelin plus bicalutamide therapy for lower urinary tract symptom relief, prostate volume reduction and quality of life improvement in men with prostate cancer: A systematic review and meta-analysis. Urol Int 2014;93(2):152-159. 


Presented by: Junpei Iizuka, MD, Tokyo Women's Medical University, Tokyo, Japan
Co-Authors: Yasunobu Hashimoto, Saitama, Japan, Tsunenori Kondo, Keisuke Hata, Toshio Takagi, Taichi Kanzawa, Kazuhiko Yoshida, Kazunari Tanabe, Tokyo, Japan

Written by:  Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA