TRT in treatment for hypogonadism and prostate cancer risk


Discussions about the pros and cons of testosterone replacement therapy (TRT) in relation to (a) stimulating risk for prostate cancer in men who have not been diagnosed and (b) recurrence of prostate cancer among men who have been diagnosed and treated often aren’t entirely clear about a very key factor. That factor is:

Why did the doctor recommend (or the patient enquire about) TRT in the first place?

So let us be very clear that the report we are going to discuss today is about risk for prostate cancer among a specific cohort of men who did not initially have prostate cancer; were diagnosed as being hypogonadal (i.e., they had abnormally low levels of serum testosterone);  and then some of them got prostate cancer later.

The data were recently reported by Haider et al. in a poster presented in October this year at the 18th annual meeting of the Sexual Medicine Society of North America in San Antonio, TX. The data are also discussed in a commentary on the Renal & Urology News web site.

Haider et al. provide data on a cohort of 776 hypogonadal men:

  • All patients were initially diagnosed with a serum testosterone level of ≤ 350 ng/dl.
  • 400/776 men (51.5 percent) elected to be treated with TRT (testosterone undecanoate 1000 mg every 3 months for up to 10 years).
  • 376/776 men (48.5 percent) opted against treatment with TRT (and represent a control group).

So this was not a randomized controlled trial, but this is a large cohort of patients studied over a long period of time.

Here is what they found:

  • The average (median) follow-up was 8 years.
  • 9/400 men in the TRT group (2.3 percent) were diagnosed with prostate cancer (incidence, 31 per 10,000 patient-years).
  • 26/377 men in the control group (6.9 percent) were diagnosed with prostate cancer (incidence, 95 per 10,000 patient-years).
  • All 9 men in the TRT group were diagnosed within 18 months of initiation of TRT.
  • All 9 men in the TRT group who were diagnosed with prostate cancer were given a radical prostatectomy.
    • 8/9 men had a Gleason score of 6 or less.
    • 9/9 men had a primary Gleason grade of 3 (i.e., there was just one patient with a Gleason score of 3 + 4 = 7).
    • 9/9 men had a pathological stage of T2
  • 24/26 men in the control group were given a radical prostatectomy (of whom 6 also had follow-up radiation therapy) and 2/26 men had first-line radiation therapy alone.
    • 26/26 men had a Gleason score > 6, of whom
      • 2 had a predominant Gleason grade of 3
      • 20 had a predominant Gleason grade of 4
      • 4 had a predominant Gleason grade of 5
    • 1/26 men had a clinical or pathological stage of T2
    • 25/26 men had a clinical or pathological stage of T3

So what is clear from this study is that, after an average of 8 years of follow-up,

  • Risk for diagnosis with prostate cancer among hypogonadal men who do not have TRT is of the order of 6.9 percent.
  • The forms of prostate cancer diagnosed among hypogonadal men who do not have TRT tend to be higher in risk (i.e., unfavorable intermediate-risk and high risk prostate cancers).
  • Risk for diagnosis with prostate cancer among hypogonadal men who are given TRT is about three times lower, at about 2.3 percent.
  • The forms of prostate cancer diagnosed among hypogonadal men who are given TRT tend to be lower in risk (i.e., low-risk and favorable intermediate-risk prostate cancers).

What is one to make of these data?

So first and foremost this study tends to suggest that TRT is generally safe and appropriate among hypogonadal men who have not been diagnosed with prostate cancer when they are initially diagnosed with low levels of serum T.

Secondly, it suggests that the forms of prostate cancer that do occur in hypogonadal men after they start TRT are low in risk and can probably (at least initially) be managed with active surveillance and without immediate invasive treatment.

Third, it suggests that TRT may actually be protective against diagnosis with more aggressive forms of prostate cancer in hypogonadal men, leading to the additional insight that …

Fourth, hypogonadism is actually (and perhaps unexpectedly) a risk factor for clinically significant prostate cancer.

This is actually the third study in the past couple of years to report that use of TRT among hypogonadal men is associated with a reduction in risk for prostate cancer. However, ideally, all of these potential conclusions will need to be carefully restudied in a well-designed, prospective, randomized, controlled clinical trial.

What we absolutely can not conclude from this study are that any of the above data are necessarily relevant to the use of TRT in men who have been previously diagnosed and treated for prostate cancer and are considering the use of TRT after their treatment in order to stimulate recovery of normal serum T levels post-treatment. That is a very different situation in a very different group of men.

18 Responses

  1. I believe you meant to say that TRT is NOT associated with increased risk of prostate cancer in hypogonadal men.

    I, on the other hand, had TRT for hypogonadism for 10 years before diagnosis with high-risk prostate cancer. Apparently there’s no connection but just sayin’.

    I’m currently scheduling a consult re: TRT with Dr. Morgentaler, who is a proponent of TRT, but as he cautions, most likely not for my case. I’m currently on ADT3 again after a small bone metastasis was found by Axumin and which I treated with SBRT and am treating with Xgeva. Serum T is < 3 ng/ml and PSA is < 0.1 ng/ml.

    I’ll report back on the consult results.

    Bob

  2. Dear Bob:

    What I meant to say was what this study says and what I am pretty sure I did say, which is that, in the patients treated in this study, TRT was not associated with significant risk for clinically significant prostate cancer and that indeed TRT appeared to lower the risk for clinically significant prostate cancer compared to no TRT in hypogonadal man.

    This does not mean that no hypogonadal men who receive TRT are ever going to get clinically significant prostate cancer. That is not a reasonable conclusion.

  3. You meant to write “This is actually the third study in the past couple of years to report that use of TRT among hypogonadal men is not associated with a reduction in risk for prostate cancer.” (The hazard ratio was 0.33).

    The association between hypogonadism and high-risk prostate cancer is well established. There are also plausible reasons for the protective effect of testosterone established in lab studies.

  4. Sitemaster:

    Haha: you’re right! I got TRT and PCa!

    Bob

  5. Dear Allen:

    I don’t think so. TRT in hypogonadal men seems to reduce risk for clinically significant prostate cancer. The alternative would be that I might have written that “use of TRT among hypogonadal men is not associated with any increase in risk for prostate cancer.”

    But all the available data are from retrospective analyses, and what we really need are data from a large prospective study (which of course may never happen).

  6. What you wrote is TRT use “is NOT associated with a REDUCTION in risk…” which is the opposite of what you meant to say. Take out the word NOT, and you’re fine.

  7. Allen:

    The word “not” was removed about 10 minutes after I first put it up, when I re-read it. I think you need to clear your cache.

    :O)

  8. See here. Just sayin’ … (unrelated to Bob’s use of the phrase… @Bob: I assume you are intimately familiar with BAT?)

  9. Bob:

    Why are you seeing Morgentaler? Is he treating patients with advanced prostate cancer with BAT?

  10. @Allen,

    Either it is too early in the morning here or there are too many negations for me to keep straight. This entire post confuses me. But what exactly is the connection between hypogonadism and high-risk prostate cancer? I am hypogonadic as a result of ADT for high-risk prostate cancer. Soon I will have my usual 6 monthly control. As I have been considering TRT, it would be good to have some information to ease discussion.

  11. Dear George:

    Your situation is very different to the situations of the men in this study. These men were all hypogonadal for normal, biological reasons before they were ever diagnosed with prostate cancer. Treatment with TRT seems to have prevented them from being diagnosed with high-risk prostate cancer.

    The risk/benefit equation of using TRT in men like you is a very different discussion. Some physicians (like Morgentaler) think this is a perfectly reasonable idea in appropriately selected patients. Others still think that this is still a very risky strategy for men who were ever treated for clinically significant prostate cancer. The truth is probably somewhere in between, and is likely to involve issues yet to be fully resolved.

    And then there is the entirely different third issue of the use of bipolar androgen therapy or BAT in the treatment of advanced and castration-resistant prostate cancer that is still experimental.

  12. Allen:

    As I said, I doubt Morgentaler has anything to offer me but I’m willing to pay $500 for a 20-minute phone consult.

    I believe that my case is interesting because I’ve never had more than one or two small mets which I then had radiated and went back on ADT3. I’m apparently still hormone sensitive with T of 3 and PSA of < 0.1. But when I stop HT my PSA doubles quickly.

    Bob

  13. Bob:

    Every case is different, but there is really nothing very unusual about having two metastases that were irradiated. Unfortunately, it sounds like it did not accomplish much for you. I’m glad you’re still hormone sensitive. I’m trying to understand what you hope to achieve by talking to Morgentaler. You clearly can’t take TRT, except perhaps alternating it with cycles of androgen deprivation (which is called bipolar androgen therapy). It is a therapy used in a small pilot trial at Johns Hopkins, and it seemed to work well in that small trial. I have not seen an expanded trial announced yet, although they have a couple of ongoing trials for castration-resistant men.

  14. @Sitemaster … Thanks for the clarification, I was awfully confused.

    About myself, the excellent Akademiska urologist thinks it is too risky to start TRT. I agreed. From the very little I have seen it looks like he was right, as the jury is out. Although the idea of a risk for recurrence seems right, given that ADT reduces testosterone to kill cancer cells, so that increasing T should increase risk, this increased risk has not been demonstrated. Nor refuted, mind you. I still agree with the urologist.

  15. Allen:

    Inasmuch as no prostate cancer has been found in any of the areas subjected to salvage or de novo radiation, I beg to differ with you that nothing has been accomplished. In terms of the pending Morgentaler consult, I’m hoping that he thinks BAT is something to consider for me even though I’m still hormone sensitive. At any rate I don’t mind spending a few bucks for his views one way or another.

    Bob

  16. When I said “Unfortunately, it sounds like it did not accomplish much for you,” I meant the cancer is obviously still in you (it is not in the irradiated places, but it is obviously in other places) and your PSA is rising rapidly, requiring ADT. Radiation will always get rid of detectable mets, but it cannot get rid of all the other ones. Whether there is any long-term benefit in getting rid of just the detectable mets remains to be seen. Maybe it slows progression, maybe not. Morgentaler is not an expert at BAT. If that’s what you’re interested in, you should consult with Denmeade at Johns Hopkins.

  17. “$500 for a 20-minute phone consult.” Good grief!

  18. William Porter
    Haha! Actually he spends 1/2 hour I’m now told plus the time to review my treatment history before the call and the time his assistant spends setting up the call, emailing details collecting data etc. Pretty standard rate based on typical doctors’ charges.

    TA
    I get what you’re saying . Since I had only 2 visible Mets in lymph nodes but had all pelvic lymph nodes treated I believe I halted progression in that vital area and bought myself a good deal of time on this planet. I could be wrong. 😰

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