Alright, well today we're going to be talking about this new thing I'm hearing a lot more
than I've heard in the past seven years of working in prostate cancer (nine years): The
M Zero (M0) space or the non-metastatic castrate-resistant prostate cancer. So is that the same thing
and if so, what is it?
Yeah, it's come to people's attention because we didn't really have a treatment in the past
and now we do. So, there's attention being placed to try and get the people that are
in that space connected with a treatment that's available. So, what it is, is a situation
where someone has had a previous treatment (surgery or radiation) and then they relapse,
and then they go on Lupron or a hormone agent, and almost invariably if people are treated
with Lupron at an early stage, their PSA will become undetectable and continue that way
for many years. But, after a number of years—well after about 10 years—about half of men will
have developed resistance to that treatment and that's signaled by a rising PSA. The interesting
thing about the M0 space is that all the scans that historically have been available (bone
scans and CAT scans and MRIs) are unable to see any metastatic disease or at least nothing
outside the pelvic lymph nodes. So that status, historically, has just been watched, but now
the M0 space can be treated with second-generation hormonal agents.
Okay, so if the scans can't pick up that there may be metastatic activity, does that mean
that there is like micrometastatic activity or really it's just localized to the prostate
or could be either one?
The consensus amongst experts is that it means that there is micrometastatic disease. So
there are small metastases, but too tiny to be picked up with our previous scanning technology.
Previously, we've talked about the symptoms of prostate cancer and kind of, like, a myth
actually, so because there's no metastatic activity, is there really any symptoms of
non-metastatic disease?
No, only symptoms are associated with many times due to low testosterone levels—get
tired and have hot flashes—but the disease itself is free of symptoms.
And so there's new drugs that have come out on the market for this new space—our new
space—but it's been around, we just didn't have drugs—as you said—for it. So, right
now we have Xtandi, Nubeqa, and Erleada, and all of those—Xtandi has been used in the
metastatic castrate-resistant space, and now they're using it in non-metastatic, correct?
Yeah, so it's not surprising that it would be effective. Medicines that can be beneficial
in very advanced metastatic disease oftentimes will even be more effective against earlier
stage smaller amounts of cancer.
Okay, so with these drugs being in the non-metastatic space, does that push the sequencing out further
so that a person can have more kind of drugs in their toolbelt and have more treatments
down the line?
Well, I don't know about more treatments, but it certainly makes or delays the onset
of metastases for a couple of years usually, and so the previously good situation, man
had a long time remission with Lupron then can be extended even longer with these new
medicines.
So, with Erleada, Nubeqa, and Xtandi, I know we have Zytiga in the metastatic space, so
how do they work differently from Zytiga?
So, Zytiga is another effective second-generation hormonal agent, by Zytiga is different than
the other three. Zytiga blocks the chemical synthesis of testosterone inside the cancer
cell; whereas, Nubeqa, Erleada, and Xtandi, they gum up the androgen receptor. The androgen
receptor is like the switch that engages the genetic machinery of the cancer cell and causes
it to grow. So, these medicines get in there and they basically glue the switch in the
off position.
So, why do they call them first-generation and second-generation hormone therapies?
Well, all the first generation hormonal therapies were designed to stop testosterone production
in the testicles. So, the blood levels of testosterone are very low. Prior to the advent
of these new medicines, we thought that cancer cells had learned how to grow without testosterone
and that turned out to not be true. It turned out that the cancer cells were learning how
to make their own testosterone internally, inside the cancer cell. So, when they designed
second-generation hormonal agents to block either the on/off switch or the synthesis
of testosterone in the cancer cell then they're able to achieve remissions once again even
though the medicines like Lupron had stopped working.
Okay, so with the first-generation, I know that men oftentimes experience side effects
like hot flashes and fatigue. Do those go for the second-generation hormone therapies
as well? And are they more intense?
They do go for the second-generation hormonal therapies. They usually are not necessarily
more intense. They do have some potential side effects that are a little different.
Zytiga, for example, can cause irritation of the liver and that needs to be monitored
for. It can cause some changes in potassium levels; that needs to be monitored for. Xtandi
has been associated with a little more intense fatigue in some cases and Erleada has been
shown to cause some rashes that you don't usually see with Lupron and those types of
agents, but considering how much more potent and effective they are, the additional side
effects seem to be pretty minor.
I know we've talked about sequencing in the past in my training with PCRI, and we talked
about where Provenge fits in the sequencing, so now that we have Nubeqa and Erleada and
Xtandi in this space, does that mean that people should be giving Provenge before? Is
it going to be approved for after those drugs? Where does it fit?
That's a good question because the way the insurance landscape sets up—because Provenge
is a very expensive drug, very few people can afford to buy it on their own—the insurance
companies insist that the patients have detectable metastatic disease. So, it turns out that
detectable metastatic disease in the lymph nodes does qualify people for Provenge, and
some of these patients that we're talking about in the M0 space do have detectable lymph
nodes, and they would be eligible for Provenge, and in my judgment, most should get Provenge,
but many other M0 patients don't have any detectable lymph nodes and their insurance
would not cover Provenge in that setting, and I expect that those men will have to postpone
the use of Provenge until after these second-generation agents stop working and 2-3 years down the
line at which point metastases would start to appear.
Well, that is our latest episode of Ask a Prostate Oncologist. If you have questions
you would to ask Dr. Scholz in the future, you can go ahead and leave them in the comment
section of this video and our team will pick them up, but we really appreciate your time.
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