So, Dr, Scholz, what is oligometastatic prostate cancer?
Well, metastatic means something that's jumped outside the prostate, perhaps into a lymph node or
bone. Those are the most common sites of spread; less commonly, prostate cancer can spread to the
liver or to the lung. Thankfully, it's pretty rare for it to spread to other parts of the body. The
word 'oligo' in greek means few and historically, when our scanning technology was poor,
if you found any spread of cancer outside the prostate
that meant that there's a lot of other hidden metastatic disease, and so people didn't try
and make a distinction of whether there were a couple metastatic spots or whether there
were numerous metastatic spots; it was all bad; it just meant that the situation was
very dire and hopeless. In many cases, the idea of oligometastatic is that—especially with the advent
of better scanning—having only a couple metastatic spots actually is nowhere near as serious
as having many metastatic spots. Now we have treatments that can be directed against those
metastatic spots; now we have scans that are much more accurate and it's possible that
those are the only metastatic spots, and in some situations perhaps those people can still be cured
with aggressive combination therapy and, say, radiation to the metastatic spots. So,
oligometastatic disease has really come to the forefront of of medical awareness over the last
five to ten years due to the improvements in technology and now a better understanding
that some of these people that do have metastatic disease may still be curable.
So, I've heard the term abscopal effect mentioned when it comes
to spot radiation. Can you explain what this is?
One reason that cancer occurs is that it has so many similarities to our normal tissues
that our immune systems don't recognize it and get rid of it. Cancer cells, apparently,
can throw up sort of a cloaking shield around their tumors and the immune system just passes
by and doesn't attack it and get rid of it. So, this can be overcome sometimes by killing a
metastatic site, say with beam radiation, and the dying cells then,
which have been killed by the radiation, release their internal proteins their unique
characteristic signatures that the immune system can then get in there and detect this for the
first time and then swim around in the rest of the body the immune system, then goes and attacks
spots of cancers in other parts of the body. So this has been observed where people have had a say
a spot on their leg zapped with some radiation and another spot well known, say, in the lung shrinks
even though that spot in the lung was never hit with radiation. So, this is not something that
happens universally. It's not even necessarily common. Probably only about, oh, 15 percent of
the time do you get a measurable abscopal effect as you're describing, but when it happens, the
radiation is actually activating the immune system to attack the cancer in other parts of the body.
So, I know we've talked a lot about PSMA which is a PET scan that specifically shows prostate
cancer. So, when it comes to oligometastatic disease, how does a PSMA scan come into play?
Well, the PSMA PET scans are finding the cancer at a far earlier stage, and so for the first time
if a PET scan—a PSMA PET scan—is showing, say, only one or two metastatic sites, there's a much
greater likelihood—not guaranteed, but much greater likelihood—that those are the only
metastatic sites, and of course, that gives hope that by treating those sites perhaps
with radiation that we may be able to cure these individuals. The idea of treating metastatic sites
with older scans—bone scans, cat scans, MRIs, even Axumin PET scans—was certainly being implemented,
but with a lot lower expectations because we knew that those scans were more likely to miss
other smaller metastatic sites that weren't showing up on the scan that can again. That
can happen with PSMA PET scans as well; there can be additional disease that's not being detected,
but it's far less likely than with the older scans, the older bone scans that we used to use.
How do you treat oligometastatic disease? Are there several treatments? Is there one treatment?
So, I would say that spot— surgeons will, if they find
oligometastatic disease in the lymph nodes in the pelvis, for example, will want to do
surgery. I'm not a big fan of that, but it is being done. Radiation is non-invasive,
it's equally effective, perhaps more effective than surgery because they can treat a field area
whereas the surgeons just go ahead and pluck out the the metastatic lymph nodes. So, radiation is
kind of the backbone of treating oligometastatic disease with say SBRT—short radiation—given over
maybe a 10 day period. The use of ancillary systemic therapies—hormone therapy, chemotherapy,
immune therapy—on top of the radiation treatment to the known sites is a strong consideration
because if there are other smaller metastatic sites that aren't showing up on the scan,
they're by definition very small and perhaps they can be eliminated with chemotherapy, hormone
therapy, or a combinations of these things. So, it's very natural, especially if the patient's in
a younger age group, to be thinking about not only radiating the oligometastatic sites, but giving
additional combination systemic therapy for insurance against the possibility of another
smaller spot that wasn't detected but maybe small enough to be eradicated
with hormone therapy or chemotherapy and thus improving the cure rate of the whole process.
So, what about Xofigo? Is that also a treatment for oligometastatic?
In theory, it could be used for that purpose and I've seen it done on a couple occasions
maybe with some benefit. I tend to think of Xofigo more for the patients that
have too many spots to selectively radiate with oligometastatic disease. We define more than five
metastatic sites as not being oligometastatic and/or diffuse systemic metastatic disease,
and that seems like a more natural type of profile for someone to use Xofigo which is a
injected radium that circulates in and radiates all the spots in the bones that have cancer. The
Xofigo doesn't work for lymph nodes, but it works nicely for bone and if there's a limited number of
spots in the bones, it seems more natural to do beam radiation in my thinking rather than
expose the whole body to radiation with Xofigo, but it can be done for oligometastatic disease.
There really isn't any clear research showing how beneficial it would be in that setting.
Earlier you mentioned that you know a spot has to be big enough to show up on a PSMA scan,
so what what is the size that it would actually show up at that point?
Well we have to remember that PSMA PET scans light up about 90 of prostate cancers, so there are
less common variants of prostate cancer that don't light up, perhaps about 10 percent of
prostate cancers don't light up with PSMA, so PSMA is not perfect in that regard, but the density of
PSMA molecules on the surface of the cancer cells will partially dictate whether it's going to light
up on a PSMA PET scan when it gets very small, but they have detected spots down to diameters as
small as two millimeters which is a huge advance compared to traditional CAT scans and MRIs where
unless, say, a lymph node showed a metastatic site that was 10 millimeters or half a centimeter—not
a half centimeter but a full centimeter—they wouldn't be called as metastatic sites so the PSMA
PET scan is a whole new realm of sensitivity for finding even very very small metastatic sites.
So, what about age? Does that have a factor in how you would treat oligometastatic disease?
Yeah, age is a fascinating thing because men who even are metastatic, let's say a limited number of
metastatic lesions can live for, you know, 5, 10, 15 years with with simple hormone treatments so
there's always, you know, a question in terms of what of many options is going
to be best for someone who's more elderly. Modern radiation treatments have become so
tolerable in the hands of experts that these days will tend to be thinking about just zapping the
limited number of spots and see how people do when they're elderly and perhaps will hold off on the
hormone treatments and the chemo treatments for those individuals, but there's always an option
of using something like low-dose Casodex which is quite effective and will keep the disease
in check for a number of years. It's often well-tolerated. Things that are happening due
to all the advances in our understanding of the disease and with many new therapies coming out,
better methods to know what's really going on with these accurate scans opens up
a lot of new options for people. We don't have the same specter of, you know, the imminency
of we're all going to die if we don't do some really aggressive thing immediately, and that
that mindset becomes far more relevant in, you know, people when they get in their 80s.
What about cure rates? Is it possible to have an absolute cure when it comes to oligo?
Absolutely, yes. We have patients that have had spots on their bones that were diagnosed
10 years ago—usually, it's a limited number one or two spots that were treated with radiation
and ancillary hormones and a short course of chemotherapy—who are in complete remission today,
who have recovered their testosterone levels have gone back to a completely normal lifestyle. I wish
it happened in everybody, it certainly doesn't. I would guess that the chances with the older
scans—we didn't have PSMA PET scans back then, but we would say maybe 10 or 15 percent of the
patients that had one or two metastatic lesions have had enjoyed very long-term durable responses.
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