So, when it comes to combination therapy, is there a sequence that you give the men
the treatments, or do they all come in at once?
No, the sequence, usually, of course, is men that have been checking their PSA every 3-6
months and now it's going up is to, first, get as good of a scan as you can get—PSMA
PET scan or maybe an Axumin PET scan—to establish that there is a metastatic lesion.
With androgen independence (i.e. castrate resistance) there's almost always a metastatic
lesion somewhere, but we may not be able to find it if it's very early state and the better
the scan, the more likely you will be in your capacity to find it. Finding that spot is
important if combination therapy is anticipated because that's they way you get insurance
coverage for Provenge which sort of kicks off the whole process. So, once a metastatic
lesion is established, we usually give them Provenge which only takes about six weeks,
and then we can start them thereafter on a combination of Keytruda and Xtandi. We tend
to pick Xtandi over Zytiga in this situation because there's some soft information, some
soft data, suggesting that Xtandi also stimulates the immune system a little bit. So, we start
the Keytruda and the Xtandi at the same time. And then once Xtandi gets starts, of course,
PSAs plummet down to undetectable levels and we continue the Keytruda for a variable period
of time. Longer and longer treatment periods can incur more side effects, so there's kind
of a balancing act in terms of what optimal treatment period is, no one really knows,
but we typically don't go indefinitely with it—3 to 6 to 9 months would probably be
a reasonable time period—and then the patients do continue on the Xtandi indefinitely, and
then the patients do continue on the Xtandi indefinitely and we observe patients staying
in remission for years with this type of approach.
So in a case where a man has, you know, had a scan, they've seen a spot, you know, they
decide to radiation it. Are you going to radiate it in order to get the abscopal effect? Is
it that immune activity that we're looking for?
So, yeah, the abscopal effect is a fascinating phenomenon that when you radiate a spot of
cancer in the body and it kills that cancer, the immune system then can come in, clean
up that debris, and then learn about the structural makeup, the types of proteins that are in
the cancer, and then it can go around and attack cancers in other parts of the body.
So, the primary reason to radiate a spot is to just sterilize a spot and kill off the
known cancer, but we always suspect that there are other smaller tumors lurking in other
parts of the body that are too tiny to be detected by the scan, and, of course, we're
hoping that the Provenge and the Xtandi will get rid of it, but by radiating that one spot,
we also believe that we are cluing the immune system in to attack those other small smalls
and that's what you're calling the abscopal effect, and it is a real phenomenon. It's
not a consistent finding, but perhaps in 10-20% of patients who have known spots—visible
spots—you'll see shrinkage in those spots without any other treatment than just radiating
the original spot; that's called the abscopal effect. It does have an enhancing effect on
immunity and probably does work in conjunction with these other things like Provenge and
Keytruda.
So, does the abscopal effect happen with any type of radiation to the bone?
Yes, indeed. It probably can. Although they believe that fast radiation that kills the
cancer quickly is probably inciting a greater abscopal effect than little bits of radiation
that go in over a long period of time. So, the fastest radiation is either Cyberknife
or SBRT which is favored also for convenience reasons, so people don't have to go back and
get a bunch of visits to the radiation therapist. They can get their treatment over quickly.
And does the abscopal effect also happen in lymph nodes as well as bones? Does it matter
where the metastatic lesion is?
As far as we know, it's the same in all locations.
I personally find immune therapies really fascinating because it's not like a chemical
or radiation or something coming into the body and killing the cancer. It's actually
your immune system killing the cancer, so that's really exciting technology. I know
this was discovered, the PD1 which is, you know, the whole mechanism of what they're
blocking in order for the cancer to be unmasked and the, you know, immune system to be able
to identify it as cancer, so how will this technology shape prostate cancer treatments
in the future?
Well, one of the things that we have—there's more research in trying to determine who's
going to respond and who is going to develop side effects. So, I think going forward, we'll
be able to pick medicines for the kind of results that we expect to get. Right now,
everything is kind of a trial and error situation. And then, of course, what's changing is the
idea of using the medicines in combination. Combination therapy has been the pathway to
more successful outcomes in all kinds of cancers, infectious disease, treatment of heart disease
with multiple medicines. The same thing is going to be true for immune therapy.
Thank you for watching. If you would like more information about anything we spoke about
today, you can visit our website PCRI.ORG. Also, please subscribe to our YouTube channel.
We come out with new prostate cancer videos every week.