Testosterone replacement therapy after radiation therapy

Many urologists these days are fairly comfortable prescribing testosterone replacement therapy (TRT) for men who have had a radical prostatectomy and whose PSA has stayed at undetectable levels for some time. However, considerations may be somewhat different after radiation therapy.

Pastuszak et al. looked at the records of 98 men (median age, 70 years) who were treated with TRT at four institutions after primary radiation therapy (brachytherapy or external beam) for localized prostate cancer. After a median follow-up of 41 months, they found:

  • Serum testosterone levels increased from 209 to 420 ng/dl
  • Median PSA was 0.08 ng/ml at baseline, and 0.09 ng/ml at end of follow-up (p = 0.05)
  • PSA of high-risk patients increased from 0.10 ng/ml to 0.36 ng/ml (p = 0.02)
  • Biochemical recurrence was found in 6.1 percent of the patients.

In a related article on the Practice Update web site, the authors note that the biochemical recurrence rate was actually lower than expected based on historical data from men not given TRT after radiation therapy.

While it seems safe to give TRT to carefully selected after radiation, the authors caution:

Nevertheless, the safety of testosterone therapy in the setting of prostate cancer can only be truly demonstrated in the setting of a prospective, controlled trial, an effort that, to date, has been limited by difficulties with patient accrual. Until such a study is available, the burden remains on the physician to judiciously select men for testosterone therapy, and perhaps more importantly, to regularly monitor them with appropriate testing and examination

It is important to also note that the men selected for TRT in this study had very low PSA levels at baseline, which is an appropriate selection criterion. An issue that can arise with TRT after radiation is that the testosterone might aggravate some incipient BPH that might cause PSA to rise even though the cancer is eradicated. In that case, monitoring PSA as an indicator of biochemical failure can become problematic.

Some studies (e.g., Pickles et al.) have noted that — for reasons that remain poorly understood — natural testosterone production may be depressed temporarily after radiation. It may be a better strategy to wait for a natural rebound in serum testosterone than to supplement immediately. Supplementing will stop the natural production of testosterone by the testes, and it may sometimes cease permanently as a result.

The other interesting issue raised by the lower than expected recurrence rate found by this study is the hypothesis that normal levels of testosterone are required to keep healthy prostate tissue healthy. Clinical trials are in place to test this hypothesis.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.


2 Responses

  1. That last point is very interesting. If confirmed it supports my belief that low T is the enemy.

  2. Dear Walt:

    I don’t think anyone is suggesting that low T levels aren’t a problem — for all sorts of reasons. That’s really not the issue.

    The issue is to what degree the use of TRT to raise serum T levels in men with abnormally low serum T levels after initial treatment for prostate cancer places patients at increased risk for prostate cancer recurrence that would not otherwise occur. Even in this small study, that seems to have occurred in 6% of the patients. In larger studies there have been reports of larger percentages of patients having biochemical recurrence after TRT … but maybe many of those patients were destined for biochemical recurrence in any case.

    Men with serum T levels in the normal range shouldn’t (in my view) be using TRT. But then there is the question of whether an age-related decline in serum T level justifies the use of TRT to raise serum T levels back up to the levels that most men have in their 30s and 40s. I don’t think we have a good answer for that question. “Normal” levels of many active agents in the human body change with age.

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