One-fourth of RT patients on ADT experience testosterone breakthrough

Among men treated with curative radiation therapy and neoadjuvant, adjuvant, or concurrent ADT, about one-fourth fail to achieve or maintain true castrate levels of testosterone suppression, according to a study from the University of British Columbia, Vancouver.

First author Tom Pickles, MD, working with Scott Tyldesley, MD, presented the findings of the study, which examined the frequency of escape of testosterone suppression and clinical factors that predicted the breakthrough phenomenon among men being treated with a luteinizing hormone-releasing hormone agonist (LHRHa). Data were obtained from British Columbia provincial databases, patient charts, and institutional records; the frequency of breakthroughs was analyzed using three a priori defined levels of testosterone: ≥50 ng/dL, ≥32 ng/dL, and ≥20 ng/dL.

The analyses included 2,196 patients who received curative radiation therapy over a 10-year period from 1998 to 2007, had serial testosterone data available, received ADT for at least 3 months, and were treated for no more than 12 months with neoadjuvant ADT.

For the cut-off of ≥20 ng/dL, which corresponds to the level achieved with orchiectomy, the breakthrough rate was 18.3% per injection. Per patient, the risk of having at least one breakthrough was 3.6% for the cut-off above 50 ng/dL, 3% for 32 to 50 ng/dL, and 20% for testosterone levels of 20 to 32 ng/dL.

Analyses of factors that predicted breakthrough using a logistic regression analytical model showed that men who were younger, obese, or who had a higher pretreatment testosterone level (>500 ng/dL) were most prone to breakthrough. The specific LHRH agonist product used was not a significant predictor of breakthrough.

"I recently reported at the 2011 congress of the European Association of Urology that testosterone breakthroughs during ADT are associated with worse PSA kinetics as an early measure of outcome," Dr. Pickles said. "The take-home message is that testosterone levels should be monitored whenever using ADT."