For the past 40 years, the formal level of “effectiveness” of androgen deprivation therapy (ADT, also known as “hormone” therapy) for men treated for high-risk, progressive, and/or metastatic prostate cancer has been a serum testosterone level of < 50 ng/dl (equivalent to < 1.7 nmol/l). However, …
It has been known for some considerable period of time that many patients appear to do a lot better on ADT if their serum testosterone level is actually driven down to something more like < 20 ng/ml (equivalent to < 0.7 nmol/l).
A new article by Merseburger et al., in the journal OncoTargets and Therapy, reviews this topic in the context of the use of ADT as a “backbone” therapy in the treatment of progressive, advanced, and castration-resistant forms of prostate cancer. The full text of this article is available (for free) on line and will be valuable reading for many prostate cancer support group leaders and educators. The authors also raise the question of whether continuous use of standard ADT in men who have become castration resistant is necessarily beneficial or needs to be assessed in the context of other treatments being actually used or considered for individual patients.
One item that is not raised in this article, but which may also be of considerable significance to risk for progression while being treated with ADT, is what a patient’s serum level of dihydrotestosterone may be. We know that it is dihydrotestosterone that is the active metabolite of testosterone that actually drives growth of prostate cancer cells, and so another unanswered question is, “What should be the formal level of serum dihydrotestosterone that is considered to demonstrate ‘effectiveness’ of therapy for men on ADT?” And that also raises the question of whether we should really be measuring serum dihydrotestosterone and serum testosterone levels regularly among all men treated with ADT (as opposed to just their PSA levels).
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: ADT, androgen, deprivation, serum, testosterone |
THE "NEW" PROSTATE CANCER INFOLINK 
Anecdotally, amongst men who I navigate, I have seen < 20 as the most frequent protocol for the past 5 years or so. When I went through ADT (2007-2010) it was < 50.
We need to read more about dihydrotestosterone from your website. I have had to stop Lupron because of heart effects. Switched to Casodex and Avodart and my PSA went to undetectable. My testosterone went up to 550 and my dihydrotestosterone went from 30 to 1.6. My PSA tracks the dihydrotestosterone, not the testosterone. It’s the Avodart that blocks the dihydrotestosterone, which is 5% of the total testosterone and a primary stimulus to the cancer … and the cause of baldness.
T Level as a Research Issue
When I served as a survivor representative proposal reviewer a number of years ago for the Prostate Cancer Research Program under the DoD-managed Congressionally Directed Medical Research Program (CDMRP), I raised this issue for at least one proposal that used < 50 as the definition of adequate testosterone suppression. I argued that the grade for the proposal should be reduced somewhat because many of us were convinced that < 20 was a far superior criterion. The push back from doctor/researcher voters on the panel was mainly that they had always used < 50, which I also suspected was the case. I did not expect to be successful but was trying to help change the culture on this important issue.
I remain convinced that < 20 should be the threshold.
It seems likely that using < 20 as the threshold for adequate testosterone suppression would make trial recruitment somewhat more difficult as fewer patients would qualify for some proposed trials. On the other hand, I'm convinced that that threshold would make results a lot more meaningful.
It would also seem wise to require DHT thresholds for proposals that involve androgen suppression. The threshold used in my own care was 5 or < 5.
While I was on Lupron only, my DHT was undetectable (i.e., < 5) with standard sensitivity DHT testing. (Is there a high sensitivity DHT test?) Pre-Lupron it was at midrange at 35. I received the Lupron as a 3-month leg injection for a total of 6 months (and initially was on 2 weeks of Casodex to reduce T surge) with T < 3.
I had an experienced nurse do the Lupron injection both times; Lupron can lose its time release (go into the blood all at once) if they hit a vein. The goal is to inject 22.5 mg intramuscularly. The dual needle injector uses one as a warning, where if the nurse sees blood indicated she needs to abort the injection and try it somewhere else After the first 3 months of Lupron I got salvage prostate bed radiation. My T is back to 320 and the PSA is < 0.02. The PSA had been 0.48 with a 5-month doubling time before ADT and radiation.
Dear George:
Much as I might like to be able to tell you more about the significance of dihydrotestosterone levels. I am limited by the relatively minimal amount of detailed clinical research on this particular topic. Most patients (even in clinical trials) do not have either their testosterone levels or their DHT levels tracked in detail, largely because since the 1990s most trials have focused on tracking PSA levels. See Jim Waldenstrom’s comment.
There are many unanswered questions on this topic. “Should baseline T and DHT levels be a consideration before starting ADT?” is one of them. With the newest research underway on bipolar approaches, we also have to ask if baseline levels are a factor is assessing who may or may not respond to BAT. This is one of the many ADT trials that need to be conducted through the NIH. Many men, myself included, have low to low normal T levels at detection but still had prostate cancer. Like PSA, I am convinced that there is no “one size fits all” number of ng/dl measurement. But there is a need to put this to the test in a trial.
The Merseburger article is well worth looking at. In addition to the topic discussed here, it has a breath-takingly thorough survey of clinical trials (completed and ongoing) of ADT in combination with various other agents. There are a lot of trials going on!