It's certainly a pleasure for me
to participate in this symposium,
and I'm going to talk to about active surveillance.
Active surveillance is the preferred form
of treatment for early stage prostate cancer.
I'd like to start out by thanking
a whole group of people who
actually helped me put this together,
it's taken a lot of many years
and great deal of work.
For disclosure, I'm a very busy surgeon.
I think prostate cancer over detection
and diagnosis or problems.
I also think as you'll hear
from this symposium that
under treatment is also a problem.
Information I will share with you
is largely my own and I will try
and walk you through it.
Active surveillance is response
to the over detection and treatment
of prostate cancer brought about
by widespread and repeated PSA
screening that occurred in the mid '90s.
It's uptake by urologist helped
pave the way for a better assessment
by the task force on the early
detection of prostate cancer.
Again, the objectives are to avoid
or delay the cost of treatment
without compromising cancer cure
and it's compliant with all major
screening and treatment guidelines.
Again, I'll show you is about timing of treatment.
Even though some men required treatment,
do they need that treatment right now.
The data I'll show you is based in about
2,000 patients who have consented for research.
Their average age is about 62, PSA 5.6.
Most of these men had low grade disease in 33,
but about 15 percent had
higher grade disease and
the average follow-up has been over six years,
some fall for 20 years
in some recently accrue to this trial.
This is the upgrade-free survival rates on surveillance.
Again, these are curves showing you
that about seven years out that
about half the patients will show
some changing grade or volume on serial biopsies.
These men go periodic imaging, PSA, and biopsy.
However, treatment rates are much better.
Only about one in three men with low-grade disease
required treatment in seven years and by
50 percent of those with
higher grade disease, and the reason for this
is most of these changes in volume or greater,
rather subtle or small,
only about one in three change is clinically significant.
What about outcomes after delayed radical prostatectomy?
I think we have the largest series
of men who have been on surveillance who
underwent surgery and about 35 percent
will have what we call adverse pathology,
higher grade disease or disease beyond the prostate.
If you look PSA free recurrence or second treatment for
recurrence rates are very similar to what
you'd expect by early treatment.
What predicts for metastases? We've looked at this,
the overall survival rate in accord is 97 percent.
Prostate cancer specific survival,
excellent at 99.7 percent.
About one percent of patients develop
metastases, mostly nodal metastasis.
What predicted for this or higher grade tumors,
more rapid PSA changes and
PI-RADS scores of 4-5 at diagnosis,
again, more adverse imaging results.
You need to consider if surveillance is right for you.
Well, some they called PSA density;
PSA divided by the gland volume.
What stage of cancer you have, what the grade is,
volume, PI-RADS score, genomics,
of course, age and health of
the patient, and very importantly,
patient and family preferences and
whether or not you have confidence in your providers.
What about new technology?
There are new genomic markers.
Again, we take the biopsy material
that expresses certain genes.
There's three commercial assays are used most often:
Decipher, Oncotype, Prolaris.
We've used all of them.
This is simply an example by Matt Cooperberg here.
Eric Klein and myself large study.
What I'm showing you here is
a likelihood of favorable pathology
on biopsy by CAPRA score.
Again, CAPRA score is a way to assess risk.
Low CAPRA score is quite variable,
but if you see on these curves here,
when you add genomic score to this,
you increase or decrease
the likelihood of failure pathology.
This is telling you that genomic scores are
adding additional prognostic information.
We have shown that the GPS score, Oncotype, again,
same thing with Decipher and
Prolaris, does predict for upgrading and
maybe a biochemical recurrence after delayed surgery.
But very important, this is a waterfall plot.
I'm going to show you here,
these are all patients, 1-271.
Blue shows those patients who
upgraded and red is no upgrades.
You can see that as you increase genomic scores,
a higher chance of
progression, but we see some patients with
favorable scores that progress
and some with unfavorable scores that do not progress.
Again, there's no GPS score,
no genomic score that completely excludes
or predicts progression by
[inaudible] one more bit of information
to use when you assess risk.
Other biomarkers, again,
one very easy one is PSA density.
A PSA density below 0.15 and PSA divided by
gland volume below 0.15
tends to predict for non-progression.
A higher PSA density, this is believed that maybe
something else going on in the prostate
that was not recognized.
Data biopsy, by one in
five patients who undergo serial biopsy will have
a negative biopsy and
either one or more negative biopsies
obviously predicts for non-progression.
MRI, again, this is very nice MRI showing
a large shadow in the right side of
the prostate demonstrated in the area there.
Lot of interest here.
I just wanted to show you that in our experience,
about 38 percent of men will show a change in
PI-RADS score again overtime on surveillance.
PI-RADS 4-5, or an
increase in PI-RADS predicts for upgrading.
Again, we use MRI quite
heavily at the time of diagnosis and then follow up.
But can you exclude a biopsy based on MRI alone?
Well, the answer is no.
The negative predictive the value of an MRI
is around 78-80 percent.
That means you'll miss about 15-20 percent of
high-risk tumors if you don't
biopsy those patients with a negative MRI.
Now just simply add PSA density to that and you
can increase the negative predictive value
to over 90 percent.
Don't use MRI alone,
but use it in context of
another biomarker PSA density being one of them.
Controversies, age, ethnicity, and grade.
Turns out that younger patients actually have
a slower rate of progression compared to older patients.
We think the younger patients,
many of whom have not completed their families,
are candidates for active surveillance
and has no significant association between
age and time to treatment or
biochemical recurrence following
delayed radical prostatectomy.
What about Gleason grade 3/4?
It turns out that 3/4 alone does not predict
for progression, it's actually volume of the 3/4.
Those with low volume 3/4
showed no increased risk
of progression or biochemical failure.
One thing you should be looking at,
paying a lot of attention to now,
is something called histologic
subtype of pattern 4.
All cells are the same.
We have shown that those men
with cribriform histology
and stromal reaction are associate
with higher genomic scores
and a higher risk of adverse pathology
or higher-risk tumor.
When you get that pathology report back
and you'd have a pattern 4 cell noted on that,
you want to know the histologic subtype.
It's not a BRCA. Two mutations
may be predict for progression,
still a lot of work being done there.
African American men, a lot of
controversy here in the Canary series that
both Matt and I participated and we saw
no difference in reclassification rates
between black and white men.
But I want to point out that
African American men make up
a small percentage of men on surveillance.
Race may be a poor surrogate
of social constructs of biology,
a lot of controversy about
race-related research currently,
and I think Mack will address this.
We need to make it less burdensome
Peter Lonergan show that we can
actually take patients and determine who's
at risk for progression.
Follow them more carefully,
those with lower risk don't need as
frequent biopsy and some don't need any biopsy at all.
But a high genomic score,
high PSA density, adverse MRI,
these patients are candidates for more careful follow-up.
Again, if you have 3/4, high volume, high genomics,
PI-RADS 4 or 5, cribriform histology,
either consider treatment or early confirmatory biopsy.
Obviously, men in poor health
shouldn't go to simply watchful waiting.
But a less intensive evaluation
is appropriate in men with a low PSA density,
negative biopsy at any time,
favorable histology, and favorable MRI and/or genomics.
In conclusion, these are the predictors
of upgrading: Age,
older age associated with
higher risk tumors; PSA density,
a PSA density below a 0.15 is protective,
above that tends to predict for
progression; high genomic scores,
whether it's GPS or Decipher; PI-RADS
4-5 predicts for progression;
higher vine Grade Group 2 disease.
Again, those who have
negative biopsies have
a lower risk of progression returns.
This is a summary of all the features that you would look
at when you try and determine what's
your risk of upgrading is on surveillance.
In some way, active surveillance is the
preferred form of treatment for men with very low,
low-risk and selected patients
with favorable intermediate-risk disease.
New technology, MRI, genomics,
and things that come will make it safer.
There's a strong interest in
lifestyle management in this group
of patients and many others.
Unfortunately, its use remains highly variable.
High rates of surveillance here in the Bay Area,
low in other areas of the country that concerns us.
As you will hear,
surveillance may be challenged by forms of focal therapy.
Many of these patients could be
candidates for focal ablation.
I'd like to thank you very
much for your attention and I'm available for questions.
Thanks so much, Dr. Carroll.
I think Dr. Carroll is
still caught up with another commitment.
I'm going to call on Dr. Cooperberg.
Matt, you need to unmute, please.
With a couple of questions.
First and foremost, Matt, could you please describe what
a PI-RADS score is and how it's used?
If you don't mind, how it's used
both as it pertains to active surveillance,
but also as it pertains to
the decision to biopsy because I was asked earlier?
Yeah, absolutely. I should have defined
that when I mentioned it earlier.
PI-RADS is a means of
standardizing
radiology reports from a multi-parametric MRI.
When I talked about MRI earlier,
we didn't really have time to get
into the nuances of what
goes into a multi-parametric exam,
but the radiologists are looking at different types
of magnetic applications to the prostate tissue.
We got a whole bunch of different sequences,
different ways of looking at
the prostate tissue in the MRI magnet.
There are typically literally dozens
of sets of images that come out of the machine
and different centers have lots of different subtleties in
the way they program a multi-parametric MRI,
which is one of the reasons that it's
for MRI specifically,
it's really important to be at a very high
volume radiology center like ours.
There's huge variation in the quality of MRI.
Not just in terms of the radiologist's reading it,
but even how well the machine is calibrated
and customized to do prostate MRI.
It's not like any CAT scan of the kidneys,
which is pretty much the same no matter where you go.
Prostate MRI is very central specific.
PI-RADS is an attempt to standardize
this very complicated and complex information.
It's a nationally agreed-upon standard whereby
PI-RADS scores is one and two are considered normal.
One is completely normal, two is BPH only.
Three means it's equivocal
whether or not there may be high-grade cancer there.
High-grade being Gleason grade group 2 or higher.
Ignoring the Gleason grade group 1s.
PI-RADS 4 means there is
probably a high-grade cancer present.
PI-RADS 5 means the radiologist is fairly
sure there's going to be
a high-grade cancer present on biopsy.
The problem as I showed you earlier, there is
a huge variation from radiologists to
radiologists in assigning PI-RADS scores.
This is true in the best centers in the world.
There is heterogeneity that
we always need to keep in mind.
That's one of the reasons most of us are not
comfortable making final decisions based on MRI alone.
MRI, as I said and Dr. Carroll alluded to as well,
is a great augment adjunctive
biopsy to help us do better biopsies.
That's the pre-diagnostic question.
You may read depending on what you read,
In the UK, for example,
you do not get a prostate biopsy anymore with
an elevated PSA unless there is a lesion on imaging.
There's something to be said for that.
The UK, they're no longer finding
low-risk prostate cancer and that's a good thing,
but there is definitely a pool of patients with
high-risk cancers who are going undetected.
That's sort of a decision.
Most of us would argue MRI is not there in terms
of accuracy for ruling out a first biopsy.
In terms of MRI and active surveillance, our approach,
we really do rely
on a confirmatory biopsy, Dr. Carroll alluded to
this, within the first year after
the diagnostic biopsy to make
sure we have not missed anything worse.
Now, after that, if the MRI is clean,
is negative, PI-RADS one or two and the biopsy is
reassuring and we get another MRI
two years down the road, and that is, again,
completely reassuring we are starting to think in
terms of delaying or
avoiding some of those downstream biopsies.
But that gets very much tailored, very much customized,
depending on the details of
an individual patient's course.
Thanks, Matt. Let me ask you one more question,
Dr. Carroll did begin to address it.
Clearly, active surveillance in men with
very low Gleason score, 3 plus 3s are important.
Can you just summarize
what patient with a Gleason 3 plus 4
biopsy should even consider a yes?
Yeah. Great question. It's nice to be
able to say as Dr. Carroll said
in his first slide in 2021,
that surveillance is the standard
of care for Gleason 3 plus 3.
It's not 100 percent, but we should be putting
99 percent of men with Gleason 3 plus 3,
maybe 95 percent on active surveillance.
Our frontier now is really figuring
out which of the 3 plus 4s matter.
As Dr. Carroll talked,
some of the factors we're looking at
things like the extent of pattern 4,
so 3 plus 4 means anywhere from 5 percent
to 45 percent of the cancer being high-grade.
Obviously, the ones where there is
almost half the cancer being pattern 4
that's more aggressive than if it's only 5 percent.
We're now subtyping the pattern 4.
The pathologists have a few different patterns
that they looked at under the microscope which they
will assign within the category pattern
4 and some of those are more aggressive than others.
The so-called fused gland
and poorly formed gland subtypes
behave biologically very similar
to the Gleason grade group 1, the 3 plus 3s.
Whereas others, you will see terms like
cribriform expense, cribriform intraductal.
These are all still within the category of pattern 4,
but we know they are more aggressive
biologically and probably less
suitable for active surveillance.
This is where the genomics really are useful clinically,
I think is in tiebreaker situations where there
is more than a tiny speck of 3 plus 4,
or even in some cases,
a very high volume 3 plus 3.
We are really on the fence
so the patients are on the fence as to
whether to do surveillance or treatment.
This is where the markers can be very helpful
in terms of breaking that tie.
Thanks, Matt. We're not really going to have
time to speak about this elsewhere.
Maybe just briefly few words
on focal therapy, and what's coming?
We intentionally did not allot time
good in this year's symposium because it's developing,
but if you can speak up just briefly.
I do have one minute of my ten minutes on surgery that I
could have devoted to
focal at the end of the talk coming up.
Oh, fine.
I think I'll take a little bit.
Why don't we come back to the question,
see if there's still a question after because I do
have a little bit of discussion.
Thank you. Okay. [MUSIC]