Debate over TRT in men with prostate Ca intensifies

Key Points

Scottsdale, AZ-Conventional wisdom says that testosterone replacement therapy (TRT) is unsafe for men who have been treated for prostate cancer. However, a small but growing body of research could provide justification for TRT in symptomatic men who have undergone definitive treatment for the disease.

Concerns over the safety of TRT in men who've been diagnosed with or treated for prostate cancer stem from the knowledge that testosterone fuels its growth.

For example, in a study involving 41 aging men with low serum testosterone levels and no history of prostate cancer, 6 months of TRT produced prostate tissue concentrations of testosterone and dihydrotestosterone no different from those of placebo-treated men. Median serum testosterone levels, however, rose from 282 ng/dL to 640 ng/dL in the treated group (JAMA 2006; 296:2351-61).

"The conclusion of that study must be that levels of androgens in the prostate do not reflect levels in the blood," Dr. Morgentaler stated.

Perhaps more important, four recent studies of TRT in men who have been treated for prostate cancer support the above findings. Three of these studies involved a total of 38 patients with undetectable PSA after robotic radical prostatectomy who were given TRT and experienced no PSA recurrence over follow-up periods as long as 12 years (J Urol 2004; 172:920-2; J Urol 2005; 173:533-6; J Urol 2007; 177:384 [abs. 1164]).

TRT after brachytherapy

The fourth study was more courageous because it involved TRT given to 31 men after brachytherapy, Dr. Morgentaler said.

"The concern with brachytherapy is that because the prostate is still present, there may still be some cancer cells present."

However, this study showed that all patients maintained a PSA less than 1.0 ng/mL with a median follow-up of 5 years (Cancer 2007; 109:536-41).

"This is a new and exciting area that has turned on its head our idea about the relationship between testosterone and prostate cancer," Dr. Morgentaler said. "In fact, the latest data show the opposite of what we used to believe: It's not that high testosterone is a problem with prostate cancer. Actually, low testosterone appears to be a problem."

In particular, a study Dr. Morgentaler co-authored showed that the rate of cancer in prostate biopsies from men with low testosterone and PSA <4.0 ng/mL was nearly double for men with more severe reductions in testosterone (Urology 2006; 68:1263-7).

Additional research shows that low testosterone correlates with higher Gleason scores, more advanced prostate cancer stage at presentation, and worse survival, Dr. Morgentaler added.

"It's paradoxical that higher grades and incidence of prostate cancer can be seen in patients with lower testosterone levels," said Donald L. Lamm, MD, clinical professor of urology at the University of Arizona, Phoenix.