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Hello, my name is Felix Feng.
I'm a Professor of Radiation Oncology,
Urology and Medicine and Vice
Chair for Department of Radiation Oncology.
Today I am going to be talking about
the Management of Oligometastatic Prostate Cancer,
From Imaging to Therapy.
Here are my disclosures.
Let's begin with a question.
What is oligometastatic disease?
It's actually defined as
a intermediate state of cancer spread
between localized prostate cancer
and widespread metastases.
It was proposed as a distinct clinical state
a number of years ago by
Sam Hellman and Ralph Weichselbaum.
Typically, it's defined as one to five metastases.
Overall, a limited amount of metastatic disease.
Now, why has
the oligometastatic space increased
in the context of prostate cancer?
Really, the answer is
because of the increasing use of PET imaging.
This is data from the increasing use of PET imaging
on the left from Melbourne
at the Peter McCallum Cancer Center.
Michael Hofman gave me these figures.
Basically, you can tell that when
this hospital got access to PSMA PET imaging,
as Dr. Hope has discussed earlier,
the number of PET scans went through the roof.
Similarly, because of Tom and Peter McCallum and others,
PSMA PET was brought to UCSF and
steadily the number of PSMA PET scans increase.
This was data from a couple of years ago.
Obviously, the numbers are bigger now.
In addition to PSMA PET,
axumin or fluciclovine PET,
is also currently available at hundreds
of imaging sites across the United States.
Both PSMA PET and axumin are now FDA approved.
Axumin is reimbursed by
Medicare and some private payers and
hopefully PSMA PET will be reimbursed as well.
I think one point to bring up is that PSMA PET identifies
oligometastatic disease at levels of low PSA.
This is our experience, we published a couple of
years ago,125 patients with biochemical recurrence,
which is BCR after surgery,
38 percent of them had a spot outside of the pelvis,
30 percent had a spot
outside of what would be considered
a standard radiation field.
These areas are red here are actually
consistent with oligometastatic disease in most patients.
This has led us to the conclusion that
the increasing use of advanced PET imaging has led to
the increased detection of oligometastatic disease and
therefore the creation of a new disease space of sorts.
The next question is, what is
the best treatment approach for oligometastatic disease?
Well, in order to understand oligometastatic disease,
we need to understand
where metastatic prostate cancer comes from.
There have been studies done looking at
cancer samples from patients who
unfortunately have died of their prostate cancer.
This is a study out of Hopkins where
they did lab genomic sequencing.
If you do deep genomic sequencing of cancer samples,
you can construct an evolutionary map of sorts within
a single patient and figure out what
spots of cancer led to what other spots of cancer.
From this data, these investigators
concluded that both the primary tumor,
meaning the one in the prostate,
and also existing metastases,
can see it or be the source of new metastases.
But it turns out that the principal mode of spread
is from one metastasis to create another metastases.
Thus, to cure oligometastatic disease,
one might need to get rid of not only
the primary tumor that started out in the prostate,
but also other metastases to
prevent them from seed new metastasis.
When I see a patient with oligometastatic disease,
I think about three different approaches with therapy.
The first is prostate directed therapy.
I think yesterday somebody asked a question in the chat.
Is there any data for radiating
the prostate in patients with metastatic disease?
It turns out that the stampede on each trial led by
Chris Barker was a randomized Phase 3 trial of radiation,
which I've abbreviated RT versus no radiation to
the prostate in men with
newly diagnosed metastatic prostate cancer.
It was a large study to over 2,000 patients and
40 percent of patients on
that trial had low metastatic burden.
It turns out that what the study
showed is that radiation to the primary tumor
improves outcomes for prostate cancer patients
with low metastatic burden and
specifically improves overall survival.
Here you can see what we call Kaplan-Meier curves.
In the y-axis for
the top two plots is what we call overall survival.
Basically, in the x-axis is time.
If 100 percent of patients lived,
the line would never dip downwards.
It would be straight horizontal across.
Every time the line dips downward,
it means that unfortunately someone
has died of prostate cancer.
The lower the line,
the worse the outcomes.
Here you can see that patients who got
radiation shown in blue
did better than patients
who did not get radiation to the primary.
If the patient had
low metastatic burden for patients
with widespread metastatic disease on the right,
there appears to be no benefit
for radiation to the primary.
On the bottom you can see failure free survival,
which is another end point.
Here what you can see is again
a benefit to radiation to the primary.
Another pillar of management for
oligometastatic disease is metastasis directed therapy.
There had been two randomized studies
which have taken patients and
either treated their metastatic disease with
radiation or not treated
their metastatic disease with radiation.
One was a STOMP study,
the second is the ORIOLE trial.
Because we're limited on time,
I'm only going to describe the ORIOLE trial.
The ORIOLE study basically randomized patients
with oligometastatic prostate cancer to
either observation or
stereotactic ablative radiation to metastatic sites.
Here you can see the outcomes.
This is progression-free survival.
Meaning, what percent of patients did
not progress after treatment.
You can see again, this is Kaplan-Meier curve.
The higher the line,
the better patients did and
the patients who got radiation shown in blue,
the better significantly than
the patients who did not get radiation.
Now, what's interesting is that in ORIOLE patients
who received the radiation had
variable coverage of their metastatic disease.
Because it turns out that
the metastatic disease was
defined by conventional imaging,
what CT scan and bone scan.
But most patients also obtained a PSMA PET to
which the physicians were blinded.
It turns out that about 19 patients
had radiation to every single spots in on PSMA PET,
and 16 patients had radiation to only part
of the total number of spots of cancer seen on PSMA PET.
It turns out that those patients who received
stereotactic radiation to all the metastatic sites
seen on PSMA PET.
These applications in blue did better than
patients who had some untreated spots.
This leads us to an approach where we want if
we're going to treat a patient with
oligometastatic disease,
we want to try to treat all the sites
of metastasis if possible.
But at the same time, it turns out
that sometimes we can't
tell how patients are going to do.
I'm going to give you a tale of two patients.
This is Patient 1.
This is somebody who underwent a prostatectomy in 2007,
had a PSA recurrence,
treated with salvage radiation and four months of
androgen deprivation therapy in 2013.
Then presented to me with
a single oligometastatic disease and
the left pubic ramus with
a slowly rising PSA that you can see up to 1.3 in 2017.
I hadn't treated him earlier,
so I saw him for the first time where
he had oligometastatic disease.
He had no other signs of disease.
It turns out though,
that when I was planning his scan or
his radiation treatment for
oligometastatic disease in 2017,
I went back and looked at his old CT scan from
2013 and I realized that the spot that was lighting up,
his current scan from 2017 was still present in
2013 and was never seen previously by the training team.
This patient had a single detectable site
of metastasis despite almost no treatment
for over four years,
no emergence of additional metastasis during this period.
This means that this patient had
very stable disease, oligometastatic disease.
It doesn't really spread anywhere else.
I radiated him in
four years later and he's free of disease.
Not on any medications.
A second patient here, very similar course,
also after surgery, also receive
salvage radiation and short-term hormone therapy.
Then he came to me with this spot in 2017, PMSA PET scan.
I again radiated the same spot.
But it turns out that even
though I made this bug go away,
there were multiple other spots that popped
up around the spot that I radiated.
Even over one month.
Not all oligometastatic disease are the same.
This first patient I showed you the tip of the iceberg,
which means the part of the cancer we saw on PSMA PET.
That was all there was and when I radiated him,
he was disease free four years later no other treatment.
The second patient, I also radiate tip of
the iceberg and then the rest of the iceberg popped up.
For Patient 1,
maybe this patient just needs
local therapy for the primary and the metastasis.
For Patient 2,
you need systemic therapy.
It turns out that there's a number of
trials that have tried to intensify
systemic therapy for patients with
high-risk localized prostate cancer
as defined by conventional imaging.
But I bet you that a number of these patients,
if they all got PSMA PET,
would have had oligometastatic disease.
One could predict that the subset of patients with
oligometastatic disease are the ones
most likely to benefit.
In conclusion, oligometastatic disease is
increasingly diagnosed due to
advances in molecular imaging.
Treatment intensification approaches involve
local therapy to the primary tumor,
metastasis directed therapy and
intensification of systemic therapy.
Randomized clinical trials are needed to
determine the importance of each and
ultimately better predictors of less aggressive versus
more aggressive oligometastatic disease are needed.
I'd like to acknowledge that our team at
UCSF and also collaborators
from other universities who have worked with me in
the context of studying oligometastatic prostate cancer.
Thank you for your time. [MUSIC]