So, Dr. Scholz, we have some questions from our YouTube channel regarding hormone therapy
and they're wondering, do testosterone levels predict how hormone therapy is
going to work or time to hormone resistance?
If people are going into hormone therapy and they have pre-existing low testosterone levels—because
we know that hormone therapy works by taking testosterone away—so if the testosterone's already
been taken away—some men are running chronically low testosterone levels—some of those individuals
won't do as well with hormone therapy. So, it makes sense to check everyone's testosterone
before you start hormone therapy to see where they're starting off. Most men have normal
testosterone levels; it's not that common to run into that scenario, but some of the men that start
with low testosterone levels are not going to do as well. Others are going to do fine. There's a
lot of variability in the cancers— many different types of prostate cancers some are exquisitely
sensitive to the removal of testosterone and others less so. So, it is possible for some men
to embark down this pathway starting off with low testosterone levels and actually do very well. So,
even though their levels are low, they're not absent, and hormone treatment is designed to
to completely eradicate all testosterone and cause the cancer cells to die.
But the other interesting thing about testosterone and long-term outcomes with prostate cancer is
that it is possible for men that have known incurable prostate cancer that hasn't been
eradicated who have been taking treatment with hormone blockade, that they are at
liberty to take holidays from their hormone blockade, allow testosterone to come back,
and be re-exposed to testosterone and not experience any long-term harms as a result.
This is so-called intermittent therapy, and intermittent therapy has been validated in
three large randomized trials showing that the people that take holidays, allow testosterone to
come back periodically, do just as well over the ensuing 10 years in terms of hormone resistance,
survival, and all the other metrics as men who stay continuously in the hormone-deprived state.
So, testosterone, interestingly, doesn't have that much direct impact on whether hormone
resistance is going to develop; it appears to be more of an intrinsic quality of the cancer cells
themselves than whether there's a lot of hormone withdrawal or a little bit;
it's more to do with what type of cancer it is.
So, a couple questions on that
what are the testosterone levels going to look like for a man who's on hormone therapy?
Well, the definition has changed. The experts like to use this dreadful word "castrate,"
"castration," "castration-resistant," and "castration levels," so they're comparing
to men who in the old days had their testicles removed surgically. Testosterone levels are
supposed to be below 50, probably below 20. Testosterone assays tend to be sort
of loosey-goosey, not super accurate, and there isn't a really— it's not like with PSA where you
can have ultrasensitive levels of down to 0.02. Testosterone levels below 20 would probably be
considered castrate by modern terms. If you go back to the older studies, they said less than 50.
The threshold for activity for testosterone removal is somewhere between 20 to 50.
So, if somebody's taking a double blockade, like two different forms
of hormone therapy, would it go would testosterone levels go even lower?
Well with perhaps with something like Zytiga that functions by stopping testosterone synthesis, it
will lower testosterone to even lower thresholds than say with Lupron alone or Firmagon alone.
Xtandi, Nubeqa, and Erleada do not actually lower testosterone levels; they just block
the activity of the existing testosterone. So, they won't lower the level any further.
I think one would wonder why not do Zytiga? Does it mean that if the
testosterone level is really low that it's going to have a better anti-cancer effect?
Yes it does, the more thorough the blockade the more effective the anti-cancer
effect. Many prostate cancers, thankfully, aren't that dangerous and so a full-on
eradication of all testosterone may be overkill in some individuals,
but in the situations where we're looking to optimize cure rates, a combination of
hormone blockade agents is going to have a more thorough blockade of the testosterone.
So, do any of these drugs like Lupron or Firmagon cause bone or joint pain at all?
It's interesting; it's a very common side effect for men to get what we
call arthralgias. This is pain in the joints. Arthritis, which is often used synonymously for
describing arthralgias. Arthralgia just means pain in the joints.
Arthritis means inflammation in the joints, and inflammation in the joints could be pain it can be
painful, but it can also be destructive. Arthralgias just mean that they hurt,
it doesn't mean there's any destructive process going on, and men that have been deprived of
testosterone commonly have arthralgias. It's a phenomena that's not been well described in the
in the textbooks, but we've observed repeatedly over and over, and it goes away when testosterone
levels come back to normal. It's something you treat symptomatically with Tylenol or Motrin
or something like that. It's not a destructive process, but it certainly can be uncomfortable.
So, Dr. Scholz, we have a patient who's been on Firmagon shots,
and he's been receiving them in the abdomen and it's getting to a point
for him that it's intolerable because of the pain. Do you have any options for him?
So, Firmagon is a monthly injection that has a slightly different mechanism of action than Lupron
and the distinct difference is that when you take Lupron for the very first time, the testosterone
will briefly rise—it's called a testosterone flare—for a week or so and then plunge down
to very low levels; whereas, with Firmagon, the testosterone levels drop immediately. So,
our typical policies in the office are to consider using Firmagon as an initiation,
which would last for a month, and then switch them over to another product such as Lupron, Eligard,
Trelstar which is given intramuscularly or under the skin and doesn't have the same irritating
properties that Firmagon does. Those other medications I just mentioned also
have the advantage of having longer durations of action—three months, four months, six months—and
patients don't have to come back to the office every month for an injection
such as the case with Firmagon. There are measures that patients taking Firmagon can use. Apparently,
if you ice the skin a little bit before the injection, if you warm the injection prior to,
you know, up to body temperature levels, it's not as irritating, but for the most part we just—
after the first shot we switch people over to a different product so we don't have this problem.
Hey everybody, it's me and my dog Hunter. We're giving him treats over here,
but yeah, go ahead and check out his Instagram at SirHuntertheDal and go ahead and subscribe
to our YouTube channel; we come out with new prostate cancer videos every week, yes we do.
you