Testosterone replacement therapy found safe in study of high-risk post-radical prostatectomy patients

Houston-Results of a retrospective study including a series of post-radical prostatectomy patients with pathology-proven high risk characteristics provide further insight into the use of testosterone replacement therapy in men with a history of prostate cancer, say researchers from Baylor College of Medicine, Houston.

The study included 21 men (mean age, 65 years) who were identified in a retrospective chart review from among 133 patients who had a history of prostatectomy and were receiving TRT for hypogonadism. High-risk features were defined as Gleason score 8 or higher (eight patients), positive surgical margins (16 patients), or positive nodal status (one patient).

The mean interval between surgery and initiation of TRT was 515 days (range, 31 to 1863), and patients' mean PSA at the start of TRT was .003 ng/mL.

"We believe our institution has collected data on the largest series of post-radical prostatectomy patients treated with TRT for hypogonadism and that we are reporting the first results from patients with high-risk features," Dr. Sathyamoorthy said. "Our findings are consistent with those of several published series examining post-radical prostatectomy patients who've received TRT.

"However, given their retrospective nature, these data may be considered for proof of concept only. Further randomized clinical trials are needed."

Controversy limits treatment's use

The use of TRT in men with a history of prostate cancer is controversial. Considering the androgen-dependent model of prostate cancer, which is based on the Nobel Prize-winning work of Huggins and Hodges, the FDA states that TRT is contraindicated in men with a history of prostate cancer. Consequently, most clinicians, including urologists, are unwilling to consider TRT in this population.

"However, this practice leaves a large population of men open to the long-term risks of hypogonadism, which include erectile dysfunction, osteoporosis, and possibly cardiovascular disease," noted Dr. Sathyamoorthy, who presented at the results at the 2010 AUA annual meeting in San Francisco.

The relevance of this issue is underscored by available epidemiologic data estimating that nearly 40% of American men older than age 45 are affected by hypogonadism, representing about 13.8 million individuals. Hypogonadism prevalence rises with age and increases by about 17% for each additional decade of life, and there is also evidence that the incidence of hypogonadism may be even higher among men with prostate cancer relative to the general population, Dr. Sathyamoorthy noted.

"A saturation model of the androgen receptor that indicates there is a limit for androgen stimulation of the prostate because of finite receptor binding capacity provides a basis for re-examining the role of TRT in men with a history of prostate cancer," he said.

At Baylor, TRT has been offered to this population since 2006, and recently, Baylor urologists launched the first FDA-approved randomized, prospective controlled study of TRT in patients with a history of prostate cancer. Patients are eligible for participation at 3 months post-prostatectomy. However, men with a Gleason score higher than 3+4 are excluded, said Dr. Khera, assistant professor of urology at Baylor.

Dr. Khera is a speaker for and receives research support from Auxilium Pharmaceuticals.