Monday, August 29, 2016

Testosterone Replacement Therapy (TRT) 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) who were treated at 4 institutions with TRT after primary radiation therapy (brachytherapy or external beam). After a median follow up of 41 months, they found:
  • ·      Testosterone increased from 209 ng/dl 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.

The authors note in an accompanying article that the biochemical recurrence rate was actually lower than expected based on historical data of men not given TRT after radiation therapy.

While it seems safe to give TRT 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 a very low PSA 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 have noted that for reasons that remain poorly understood, natural testosterone production may be depressed temporarily after radiation (Pickles et al.) 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.

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