TRT after radical prostatectomy for localized prostate cancer in hypogonadal males

A new paper just published in the Journal of Urology addresses (again) the controversial issue of whether the use of testosterone replacement therapy (TRT) is appropriate as a management strategy after first-line treatment for hypogonadal patients. As will be well known to many readers of this news blog, the reason that TRT is considered to be controversial in men with a history of prostate cancer is because of the concern that it may stimulate re-growth of the cancer.

Pastuszak et al. have carried out a retrospective review of data from 152 patients managed at their center who fell into one or other of two groups:

  • Hypogonadal men who were diagnosed with prostate cancer, treated  by radical prostatectomy, and subsequently treated with testosterone supplementation (Group A, n = 103)
  • Non-hypogonadal men who were diagnosed with prostate cancer, treated by prostatectomy, but not subsequently treated with testosterone supplementation (Group B, n = 49)

So that we are quite clear, “hypogonadism” in men is a condition in which the body doesn’t produce enough testosterone, the hormone that plays a key role in masculine growth and development during puberty and that profoundly affects things like vigor, libido, muscle mass, and other factors in males later in life.

The “normal” lower limit of serum T that is used to define hypogonadism is 300 to 375 ng/dl. However, in this particular study the authors included patients who had clear sympotms of hypogonadims, even if their serum T level was > 300 ng/dl. (The highest serum T level of any of the patients defined as hypogonadal in this study was actually 513 ng/dl.)

All patients evaluated in either Group A or Group B had to have one or more “undetectable” levels of PSA post-surgery. The patients were all, also, classified into two risk groups:

  • A “non-high” risk group
    • 77 men in Group A were of “non-high” risk.
    • 34 men in Group B were of “non-high” risk.
  • A “high” risk group (including men with one or more of the following: pathologic Gleason score ≥ 8, positive surgical margins, or positive lymph nodes)
    • 26 men in Group A were at “high” risk
    • 15 men in Group B were “high” risk

Here are the key results of the retrospective analysis:

  • Median follow-up from TRT initiation among men in Group A was 27.5 months (range, 6.2 to 189.3 months).
  • Median follow-up after surgery among men in Group B was 16.5 months (range, 1.7 to 77 months).
  • There were no significant differences between non-high risk and high risk men in Group A with respect to PSA levels or any serum hormone levels.
  • There was a higher occurrence of pT3b tumors among men in Group B compared to men in Group A.
  • Among men in Group A
    • There were significant increases in serum T levels at almost all follow-up time points
    • There was a small but statistically significant increase in PSA levels among non-high risk and high risk men at 18-24 months after initiation of TRT.
    • Median PSA velocity was 0.002 ng/ml/yr (range, 0.001 to 0.003 ng/ml/yr).
    • Biochemical disease recurrence was observed in 4/103 patients (3.9 percent).
  • Among men in Group B
    • There were no significant increases in PSA levels.
    • Median PSA velocity was 0.0002 ng/ml/yr (range, –0.001 to +0.010 ng/ml/yr).
    • Biochemical disease recurrence was observed in 8/49 patients (16.3 percent).
  • All biochemical recurrences occurred among men in the high risk patient subgroups.

The authors are careful, to note that, “the median duration of our follow-up period remains relatively short in the context of the natural history of prostate cancer, and these data may not be representative of longer-term trends.”

The “New” Prostate Cancer InfoLink recognizes that there is a gradually increasing body of evidence to suggest that  TRT may well be safe in the management of carefully selected men previously treated with prostate cancer who have undetectable PSA levels post-treatment. However, we concur with Pastuszak et al. when they point out that:

  • Reported global experience with TRT among men treated for prostate cancer is small, with only about 600 patients (many treated in very different ways) evaluated to date.
  • At this time, the use of TRT in many with any history of prostate cancer should be conducted under a very rigorous surveillance protocol.

3 Responses

  1. I have been using a compounded TR Cream (8% in Lipoderm) for the past 2 years after having brachytherapy in December 2009. My PSA was 0 at the time I started TRT in November 2010 and has slowly risen in small increments to 1.5 ng/ml over the past several years. Would you consider this within a normal range of increase due to the increasing testosterone levels (300 to 500 ng/dl) or should I be concerned? My urologist first started me on Lupron injections in 2007, although my tumor was totally contained and had not metastasized and was of low grade with a PSA of 10 ng/ml. After 2 years of Lupron injections, I was totally hypogonadal, with all the symptoms, including extreme muscle loss, bone mass loss, weight gain, cognitive impairment, breast enlargement, and erectile dysfunction and with a prostate volume approximately 50% smaller than a normal-sized prostate when the seed implant procedure was performed. Since starting the TRT I have noted very positive changes and improvements in all phases of my life that had been devastated by the prior Lupron injections, with no negative side effects other than a slow rise in my PSA and the ongoing breast enlargement (which I have been advised can now only be corrected with major surgery). My question: at what point should I ask for more comprehensive tests for the possibility of recurrent prostate cancer?

  2. I am not a physician, and there is an awful lot of information missing here for anyone to be able to fully understand your overall course of therapy from diagnosis to date. (The course of therapy you describe sounds a little strange.)

    You really need to ask this question of the physician who is treating you now, but my general sense would be that if it has taken 29 months (since November 2010) for your PSA to rise to 1.5 ng/ml, then there is probably no need to be overly concerned as yet. An awful lot actually depends on things like your age, your Gleason score at the time of your original biopsy, and your current PSA doubling time based on your last three PSA results.

  3. This article is about TRT after radical prostatectomy for localized prostate cancer in hypogonadal males and it is very misunderstood and controversial topic among scientists. This therapy is very helpful for me. I’ll follow this therapy. Thanks for giving nice article.

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