Delayed LHRH Agonist Dosing Doubles Castration Levels in Prostate Cancer

E. David Crawford, MD

The administration of luteinizing hormone-releasing hormone (LHRH) agonists in patients with prostate cancer was significantly more delayed in clinical practice than in pivotal clinical trials, according to findings from a retrospective study published in The Journal of Urology.

Of 22,860 patients who received an LHRH agonist in their treatment course, 84% and 27% were delayed in the 28-day and extended-month analyses, respectively.

“This study of ADT dosing in clinical practice showed that 84% of LHRH agonists were administered later than scheduled 28 days or multiples thereof in pivotal trials with consequent T elevations. It is highly likely that increasing adherence to ADT dosing schedules would improve T suppression in patients with prostate cancer and potentially improve clinical outcomes, including delaying disease progression,” said lead study author, E. David Crawford, MD, a professor of urology at the University of California, San Diego, in a statement to OncLive.

LHRH therapy is a type of androgen deprivation therapy that lowers the amount of testosterone in the body, without which prostate cancer cells cannot continue to grow. Available LHRH agonists include leuprolide, goserelin, triptorelin, and histrelin.

In the retrospective analysis, investigators from more than a dozen institutions analyzed the records of 22,860 patients with prostate cancer who received LHRH agonists from January 2007 through June 2016. The data collected from an integrated source including claims from hospitals, multispecialty practices, and small group practices, as well as physician offices. These patients were cared for by urologists, oncologists, or other specialists.

Analyses were done using 2 definitions of month, including a 28-day month, which was considered late if the dose was administered after day 28, 84, 112 or 168. The second definition of month was an extended month, which was considered late if the dose was administered after day 32, 97, 128 or 194 for 1, 3, 4 and 6-month formulations, respectively.

The percentage of late dosing, related testosterone values, and the frequency of testosterone and prostate-specific antigen (PSA) testing were evaluated.

Additional results showed that 60% of injections were delayed by more than 1 week and 29% of injections were delayed by more than 2 weeks in the 28-day month analysis.

Testosterone assessment was done in only 13% of patients, and PSA measurements were performed in 83% of patients.

Regarding testosterone values, 4% were greater than 50 ng/dL for early and on-time injections in the 28-day and extended-month analyses. However, 15% and 27% were greater than 50 ng/dL when the injections were delayed in the 28-day and extended-month analyses.

For early and on-time injections, 22% and 21% of testosterone values were greater than 20 ng/dL in the 28-day and extended-month analyses. However, 31% and 43% of patients who received delayed injections had testosterone values exceeding 20 ng/dL in the 28-day and extended-month analyses.

Moreover, the mean testosterone value was higher in patients who received a delayed injection in the 28-day month and extended-month analyses, almost double the castration level, at 49 ng/dL and 79 ng/dL, respectively. Among patients who received an early or on-time injection, the mean testosterone value was 21 ng/dL in both analyses.

Reference

Crawford ED, Twardowski PW, Concepcion RS, et al. The impact of late luteinizing hormone-releasing hormone agonist dosing on testosterone suppression in patients with prostate cancer: an analysis of United States clinical data. Jour Urol. 2020;203(4):743-750. doi:10.1097/JU.0000000000000577