[MUSIC]
Hello again. I'm Mathew Cooperberg
and I'm going to now go over some of
the basics involved with
surgery for localized prostate cancer.
Just to start with some very basic orientation in
terms of where the prostate is and what it does.
The prostate is a reproductive organ.
It's job is to make seminal fluid and to help
push that fluid forward at the time of ejaculation.
You can see from a side view of anatomy here,
the prostate sits at
the outlet of the bladder, which is here.
It sits behind the pubic bone,
which is the bone that can be felt above the penis.
It's sits in front of the rectum.
Biopsies are typically done through
the rectum into the prostate this way,
and it sits above the pelvic floor.
The muscles of the pelvic floor,
which include the sphincter muscle complex
here are what keep men dry.
Urine passes out of the bladder,
through the prostate, through
the urethra and ultimately
of course at the end of the penis.
Then the final fact is that the nerves that drive
erections from right here here
along the back surface of the prostate.
Radical prostatectomy means removing the prostate
away from the bladder and away
from the sphincter muscle here.
We sew the neck of the bladder down to
the urethra to recreate this connection.
The seminal vesicle are removed
at the time of the surgery as well,
as this the central portion of the urethra
running through the middle of the prostate.
In some cases we also do
a lymph node dissection if there is a risk of
cancer cells being out in
the nodes and the lymph nodes are not pictured here.
They run along the inner surface of the pelvic bones.
Surgery can be done in different ways.
Traditionally was done through an open incision
underneath the belly button.
Today, the vast majority of
the prostatectomy cases done at UCSF and
most other high volume centers are done with what's
termed as robot-assisted laparoscopy
using the daVinci machine.
This machine is not actually a robot but it has autonomy.
The company keeps promising that with
next version we can push start and go get coffee.
That of course is still a long wait away.
What this system is in reality is
a virtual reality system
that lets us operate through small incisions,
typically five or six small incisions in the abdomen
using a 3D virtual reality system where we're driving
robotic instruments that actually
have more planes and motion than
the human wrist to operate in
small confined spaces like the male pelvis.
It is critical to recognize, however,
that the robot is just a tool and that
ultimately it outcomes are driven by
surgeon skill and experience,
not by the question of whether it's
an open or robot-assisted prostatectomy.
An analogy that I've always liked,
although I don't claim credit for it,
is if you give Yo-Yo Ma Stradivarius violin,
he's going to sound much better than he
would on a cheap violin.
You give me a violin, you give me a Stradivarius,
and you leave the building because I don't play
the violin and a Stradivarius
does not make me a violinist,
and it really is a good analogy.
Now, the robot does not make
a bad surgeon safe or a mediocre surgeon good,
but in the right hands it
allows us to minimize blood loss,
speed recovery, and perhaps improve functional outcomes.
It's also critical to realize
that volume and experience really do
matter and that most surgeons actually do
relatively low volume surgery in this country.
On the right here is a table
from an older study which probably still
applies looking nationally at the surgical volume here.
The top line here is somewhat shocking statistic that
over a quarter of prostatectomies in America are done by
surgeons who do one case per year.
In fact, if you do 50 or more per year,
that puts you in the second percentile.
On the left are data from the National AQUA registry,
which I help run for the American Neurological
Association, showing similar numbers.
This is by practice,
not by individual urologists,
but here are the annual case volumes range from
just one or two cases up to
well over 300 for some of the larger groups.
What's involved with the prostatectomy?
Well, this is of course, a surgical procedure
requiring general anesthesia.
There are the typical short-term risks of any operation,
things like bleeding and infection,
injuring organs around the prostate like the rectum.
These are typically very low for men who have not had
a lot of prior belly surgery
or prior radiation to the prostate.
The typical hospital stay is just one night.
We lead a catheter, which is a little tube draining
the bladder for one week after surgery.
Men are advised to stay on
relatively light activity for about 4-6 weeks afterwards.
Now, prostatectomy does have
the somewhat minor advantage of
allowing the final Gleason grade
and stage to be determined.
We get that result within
a week or two after the surgery.
Critically within two months after the surgery,
6-8 weeks the PSA should fall to
an undetectable level and
ideally stay undetectable forever.
As the PSA rises after surgery,
we usually get that signal relatively quickly.
Additional treatment such as
radiation therapy, hormonal therapy,
or other systemic treatments can
be brought to bear in these cases.
We also had the advantage of being
able to send off for final tumors for genomic analysis.
Now, we're going to talk more about
this later on in the course today.
But genomics give us a bit of
a sharper crystal ball picture
as to how the cancer may behave
for the long-term and can help us make decisions
about timing of radiation after surgery.
This is one example study
showing that for men with favorable genomics,
which is over here on the left,
very few men actually progress to metastatic disease.
In this graph here, each step up is a man who developed
metastasis up to to 10 years over time,
from time 0 up to 10 years.
Very few men ultimately develop metastasis regardless of
the PSA at the time of
radiation from men with a low genomic score.
On the other hand, men with a higher decipher score.
Now, we see a real advantage to
treating early when the PSA is less than
0.1 as opposed to waiting until
it's higher than the 0.1-2.5 range,
or even over 0.5.
Now, we see a far lower rates of metastasis when
the radiation is given
early after surgery in
the setting of a high genomic tests.
We're able now to get even more information out of tests
like this and we're able to make some predictions.
These are not prospectively validated yet,
but we can make predictions about
response to other types of treatments
as well based on
the tissue to get to at the time of surgery.
Now, there are the well-recognized downsides to
surgery mostly focused on
urinary leakage and erectile dysfunction.
When we remove the bladder catheter,
most men will have some degree of leakage.
Usually when the surgery is done at
UCSF or a comparable institution,
we're usually talking about a few drops
of urine that leak with coughing,
straining, sneezing, laughing,
anything that tenses up the belly muscles.
This is usually minor.
We're usually talking about a few drops here and there,
not an open water faucet.
Typically pads [inaudible] are sufficient.
We're not usually talking about
diaper level and continents even early on.
The typical time, that pads are required as
a few weeks to a few months on average.
But the recovery can go on for up to a year.
In our hands at UCSF by one year,
over 90 percent of men will typically be
dry and can get rid of the pads.
Most of the remainder will have
relatively minor leakage manageable
with the single pad per day.
Bad long-term leakage is quite uncommon
for men that have not had
prior radiation therapy or other complicating factors.
Persistent leakage can be addressed with
additional procedures or other interventions.
We should also point out that men who have a lot
of obstructive symptoms of baseline,
either from a bad cancer or much more commonly from BPH,
benign growth of the prostate,
which is actually not related
to prostate cancer risk at all,
but typically co-exist in many men as they get older.
Well, by taking the prostate out of the picture,
we can actually alleviate the obstruction.
It's actually not that uncommon in this day and age
for men to have better urinary function overall
a few months down the road after surgery than they do at
baseline if they have obstruction they're going in.
Now I will say that the big caveat
here is that when we do surgery on men who have
had prior radiation therapy or
other prior whole gland treatments,
focal therapies, then the urinary recovery
is much more difficult to
predict and is often much slower.
In terms of erection recovery,
erections are driven by the nerves that
run right along the backside of the prostate.
Erection recovery is driven by age,
by function going in,
of course, we don't make anybody's reactions
better by doing anything to
the prostate and how much nerve preservation we can do.
We can usually spare at least some of the nerve tissue,
even in the setting of aggressive cancers,
and the extent to which we can spread the nerves is
driven by factors like the tumor stage,
whether it's confined to
the prostate or outside the edge,
and by imaging findings,
whether MRI and ultrasound give
us an indication that the cancer may
be outside the edge or not.
Almost all men will have a drop in
erection function at least initially,
and then the recovery is
typically much slower than the urinary recovery.
It can go on for up to two years
after the surgery because
the nerves need to recover all the way from the spine.
It's critical to realize there is
no ejaculation ever again after the surgery,
orgasm is possible, but there's no fluid
produced and no natural fertility for that reason either.
As I said, the recovery
can go on for up to two years and often
the greatest recovery is in
the second year after surgery.
About two-thirds men will typically get back to
baseline within two years after surgery.
But again, this is variable depending in large part
on baseline function and other factors.
We typically are as
aggressive as men want to be in terms of
canal rehabilitation starting with medications
or using one of many other options available to us
for men who have a drop in sexual function after surgery
or any other type of treatment for prostate cancer.
Now I will stress here that
inappropriate care is never high quality,
and no matter how well the surgery is done,
no matter how quickly
urinary and sexual function come back,
if this was a tumor that did not need to happen for
a low grade small volume
Gleason 3 plus 3 tumor, for example,
that is not high-quality care and I stress again,
that at UCSF our focus is
really on intermediate and high-risk disease.
A brief word on focal therapy,
this is the equivalent in prostate cancer
as a lumpectomy as would be done for breast cancer.
This is a case that I saw literally just this week.
A small clearly visible tumor
here where all the rest of the biopsies
of the prostate are negative.
Well, why should we treat the entire prostate here?
Why can't we treat just this little lesion?
In fact, there is growing interest in
focal therapies for carefully selected cases.
We still have no interest in
overtraining Gleason grade group 1,
those 3 plus 3s.
But for great group 2 tumors that we can see on MRI or
ultrasound and where the other biopsies are negative,
we are increasingly interested in the idea of
focal therapy to destroy
the tumor and leave the rest of the prostate alone.
We've used cryotherapy for many years,
that's freezing the prostate.
We have a new high FU system that's
high intensity focused ultrasound
and there's lots of other treatments out there,
and the ablation modality,
how we destroy the tissue is probably less
important than knowing what it is that we're treating.
In summary, prostatectomy remains one
of our gold standard options for
men with intermediate to high risk prostate cancer,
and it's important to realize for
high-risk disease it is often the first step
in a multi-step effort
to cure a high-grade prostate cancer,
and maybe well combined with radiation,
systemic treatment and others.
The risk of urinary leakage are
higher higher surgery than with other treatments.
On the other hand,
risks of urinary and bowel irritation are lower,
and again, the surgical outcomes really are
very searching and center specific.
Thanks for your attention and
we will look forward to the discussion.
Thanks Dr. Cooperberg.
There's a couple of questions.
Do you want to talk briefly about you said you addressed
during the live session about lymph node dissection?
To what extent, why is it done?
Does it have an impact on outcome?
Yeah. I didn't talk much about it in the talk,
but lymph node dissection remains an important part
of the surgery for men with higher-risk disease.
Because lymph nodes are usually the place that cells will
escape first when they do escape the prostate.
Traditional imaging like CT
and MRI typically will not show
us enlarged nodes unless there is over
a billion cells in one of the nodes,
that's what it takes to actually enlarge it.
With newer imaging like
PSMA PET that we'll be talking about tomorrow,
we can drop that threshold significantly.
We can see smaller metastasis in the nodes.
But still microscopic disease we still will not see.
We have different risk systems,
similar to the ones Dr. Feng talked about earlier,
which can help us make predictions,
but the likelihood of
microscopic involvement in the nodes,
and when the risk is high enough to
warrant doing the node dissection, we usually will.
It adds somewhere
between 30 and 40 minutes to the surgery,
it does not add much in the way of risk
except for the risk of a lymphocyte,
which is an accumulation of lymphatic
fluid after the surgery,
which usually does not cause any symptoms.
As far as the question about extended
versus standard lymph node dissection,
there's more areas of
controversy in prostate cancer
than we know what to do with.
It's actually a very difficult study,
very difficult question to answer.
Memorial Sloan Kettering actually, God bless him,
ran a randomized trial of over 1200 patients where they
randomized matrix extended versus
standard lymph node dissection.
The problem is at the end of the day,
the average number of nodes removed
in the standard group was 12,
and the so-called extended group was 14.
Despite their best intentions,
either the surgeons were not
capable of really scaling down to
a limited detection or scaling
up to a particularly aggressive dissection.
I think the jury is still out on that.
There has never been a study that's shown that doing
more node dissection improves cure rates.
We know that surgery alone does cure
about 15 percent of men with positive lymph nodes,
by which we assume that we're curing at least a subset
of the prostate cancers by doing a node dissection.
But that has really not been well
established in randomized trials.
We're very interested in this question,
it's an area of active study for us at UCSF.
Actually one area of innovation here
which may not come up tomorrow,
going to Kissimmee session is we're
starting to run intraoperative Kissimmee energy,
where we're actually attaching
a Kissimmee directed molecule to a fluorescent tag,
that we can identify during surgery.
We have a special camera for
our version of the surgical robot at UCSF,
where we can actually turn on the light,
you can think about it a little bit like
a black light whereby a node
that actually has Kissimmee
positive prostate cancer cells
in it will light up green.
We're in very early stages of this,
but the whole base of that will allow us to really focus
only on those lymph nodes
that might have cancer cells in them.
While we're talking about PSMA,
is there a role for preoperative PSMA pet scan?
Yeah, great question.
Another area of controversy.
Yes, but we don't
necessarily always know what to do with the results
because we've got decades and decades of
experience validating the role of
surgery and radiation therapy for men with
so-called m-0 high risk prostate cancer.
We have known all along that many of those men
have microscopic metastatic disease,
and yet we know that
surgery and radiation therapy are helpful.
Well now what we're doing is
driving what's called a stage migration.
Meaning we're taking men who we call
the m-0 because their bone scan was negative.
Now we're saying they're M-1
because the PSMA pet is positive.
Do we now say you're disqualified from surgery radiation?
That's probably not the right thing,
so we're not yet clear what to do with the information.
I will say when we get
a PSMA pet before surgery, if there is, for example,
a lymph node a little bit out of
the template that we would normally go after,
we can take out that additional node during the surgery.
Sometimes we may find one spot in the pelvis,
for example, on
a PSMA pet where the bump channel is negative.
Again, there's no guideline here and there's
no randomized trials to tell us what to do.
We are typically offering
the standard local therapy
discussion with the understanding that
that spot is also going to need
radiation therapy after treatment.
I think it's really we're at
the bleeding edge of where the sciences and,
we are going to await new trials,
we're actually running some of those trials here
at UCSF about surgery
and radiation therapy.
So it's a little bit [OVERLAPPING].
I think it's probably fair to say that PSMA pet is not
approved or the pre-operative setting is approved,
FDA approved for the climbing PSA setting.
If we're doing it,
we're doing it off-label
as part of a study and self- [inaudible],
it's not yet considered the standard of care.
Definitely.
Great.
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