EAU 2019: Switching from GnRH Agonists to Antagonists for Castration-Resistant Prostate Cancer as a Second-line Hormonal Therapy: A Multicenter Prospective Study

Barcelona, Spain (UroToday.com) LHRH agonists are the most frequently used drugs for androgen deprivation therapy (ADT) in prostate cancer. Using these drugs and achieving castrate testosterone levels lower than 20 ng/dl correlates with improved disease-specific survival in advanced prostate cancer patients. The testosterone levels may rise above castrate levels between administrations, especially if it is delayed.   When patients have an increase in PSA levels, it is unclear whether these rises are due to late administrations, inadequate treatment efficacy, or disease progression to castrate-resistant prostate cancer (CRPC). Variability in the duration of ADT agents in maintaining lower levels of testosterone may also be relevant.

In this study, the authors aimed to determine the scope and impact of late administrations of ADT in prostate cancer patients. The authors evaluated the timeliness of LHRH agonist administration, subsequent rate of testosterone breakthrough above 50 ng/dl, and frequency of testosterone and PSA testing prior to dosing. Administrations and testosterone tests were defined as “late” if the drug was not administered after day 33, 98, 129, or 195 for 1-, 3-, 4-, and 6-month formulations, respectively, as seen in Figure 1.

Figure 1: Methodology 
EAU 2019 adm and t test timeline

A total of 26.9% of LHRH agonist administrations were late: 14.4% were <=1 week late, 3.1% were between 1-2 weeks late, and 9.4% were >2 weeks late. The percent of late administrations was high across all formulations: 53%, 19%, 26%, 25% for 1-, 3-,4- and 6-month formulations, respectively (Figure 2).

Figure 2 – Proportions of late administrations:

EAU 2019 fig 2 proportions of late adm

A total of 28% of testosterone values exceeded 50 ng/dl when administrations were late. In contrast, only 4% of testosterone values exceeded this level when doses were administered early or on time (Figure 3). Patient demographics are shown in Table 1.

In conclusion, across LHRH agonists, greater than a quarter of administrations were late. Among late administrations, about half were >1 week late, and more than a third were >2 weeks late. Late administrations were correlated with ineffective castration over 19% of the time when comparing across all formulations. For injections, testosterone levels were not monitored as frequently as PSA levels. Therefore, considering the presumed clinical benefits of maintaining effective testosterone suppression through the course of ADT, clinicians should administer treatments within the approved dosing instructions, routinely monitor testosterone levels, and consider prescribing treatments with the appropriate dosing interval to maintain testosterone at castrate levels at all times.

Figure 3 – Proportion of T tests with levels above 50 ng/dl by the timeliness of administrations – by formulations:
EAU 2019 t test timeliness of administrations

Table 1 – Patient demographics:
EAU 2019 table 1 pt demographics
Presented by: Rumiko Sugimura, Yokohama City University Medical Center, Department of Urology and Renal Transplantation, Yokohama, Japan

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 34th European Association of Urology (EAU 2019) #EAU19, conference in Barcelona, Spain from March 15-19, 2019.