Yes, the less morbid procedure,
or less morbid alternative to surgery and radiation.
I'll be going over the basic principle of
it and ideal patient for focal therapy,
the current guideline,
outcomes, and then future directions.
As I previously mentioned
that and others have mentioned that prostate cancer is
a spectrum of disease and it ranges
from low to very high-risk cancer and UCSF,
we believed that the treatment should match
the extent of the disease and the patient.
Focal therapy has a space in the spectrum,
particularly between low and intermediate-risk disease.
I think in the future, we may get
to in the case of relapse and metastatic setting.
Now improvement in
cancer localization and risk assessment
have resulted in a more wider adoption
of focal therapy across the United States.
Focal therapy has been around for years,
but because of the inability
to target these areas accurately,
that's why it hasn't been widely adopted.
But now it is more common because of advanced technology.
Focal therapy is treating a section or
a focus area of
the prostate to minimize the side effects.
Often as you know,
treating the whole gland has issue with
urinary function and sexual function
whereas treating a focus area or
section of the prostate and
you maintain your sexual function,
including ejaculatory volume,
you maintain your urination function as well.
That could be very attracted to
men in certain risk spectrum.
The whole premise of focal therapy
is that if we target the dominant tumor,
the problem tumor that we
can really minimize the side effects.
This is a paper published many years ago looking
at lean as tracing of
a cancer that has spread throughout the body,
so looking at the copy number analysis
of genes throughout the metastasis,
they can actually trace it back to
one clone in a prostate.
Prostate cancer is 70 percent or
higher of those men who have multifocal disease,
but the dominant tumor,
maybe the responsible one.
If we can accurately identify the clone or
the metastatic clone within
the prostate and targeted precisely,
then we don't have to treat the whole land and prevent
metastasis and that's the whole premise.
Resource at UCSF lead by Dr. Carol Health,
also shine a little bit more light on this.
This is a study of over 1,000 men analysis valence,
and most of these men have multiple biopsies throughout.
You can see here most of the progression
occur in the area of the dominant tumor,
so they are a candidate for
focal ablation at the first biopsy.
They remain so even after four or five biopsy
as we surveyed their cancer
throughout the five years or 10 years period.
Who are the ideal candidate for focal therapy?
It has to be localized intermediate-risk cancer
of the patient who is in seven cancer.
Also in carefully selected recent six cancer,
or sometimes unfavorable intermediate easy.
Now the tumor location is important.
It has to be away from the urethra and the rectum,
and also the patients
have to agree to lifelong surveillance.
I often tell the patient this is not a cure,
is to ablate the main dominant tumor,
so if they have to still go on surveying an after.
There's multiple way we can ablate the tumor.
There's a focal and then we can target
the quadrant or sometime hemi-ablation
would be half of the prostate,
or we can use a hockey stick approach
if these are the location of the tumor.
The patient's selection,
so most of the patients that I offer those to must have
an MI fusion biopsy to make
sure we don't miss any other cancer.
Sometime I order a PSMA PET scan for staging.
Tumor location is often how we
pick a certain type of energy to ablate the cancer.
Also, I require all patients who have a rectal exam
and an ultrasound exam to see if they have calcification,
for instance, in the prostate.
This would interfere with ultrasound,
this calcification will reflect off
the sound and lactose
the gnosis that we've gone through the rectum.
Those are the selection of the patient.
Now how do we do it?
There's multiple ways we
use the different energy source to target the cancer.
One is a long gap or freeze it.
You can use brachytherapy or
the radiation seed to put it in there.
Also transrectally, we
can use ultrasound to oblate the cancer.
Depends on location.
If you have an anterior tumor, typically,
I would favor focal cryotherapy,
posterior tumor near the rectum then
ultrasound would be a better approach
to enrich that tumor.
There's now a laser that we can
use laser right into the tumor and applying heat there.
There's also a focal irreversible electroporation,
this is using electrode but around the tumor and deliver
electric shock through it to destroy the tumor.
Focal therapy, focal brachytherapy,
cryotherapy and also using TULSA.
This is to apply ultrasound through the urethra.
In cases where a patient has
a large median lobe
or a lot of symptom from benign enlargement,
we can use that to tackle the media,
the transition zone also.
For focal therapy at UCSF,
we focused on ultrasound and cryotherapy.
Cryotherapy has been around for many years now.
They recently started a high food program last year,
and this is done through the robotic approach
where your patient have to go under general anesthetic.
We use an MRI to guide ablation,
so we target using
the MRI and ultrasound and then
we'll plan for the family.
The whole thing takes about an hour or so.
The focus ultrasound really apply heat to the tissue.
Each of the section is about
1.7 millimeter is how we ablate them
and you can see there's a drop
Steve Javac and temperature around it so that way we
can minimize the effect around it.
This is an actual ablation planning that I've done.
This is a fusion of a MRI with the ultrasound,
so you cannot see the tumor right into the 3D image.
Here is a tumor, here's a plan.
Typically, I would ablate
about 5-7 millimeter beyond
the tumor to get an adequate margin,
and this is actually ablation that's going on.
This is what the tissue looks like.
Twenty-four hours later, the tissue is heated up to
85-95 degrees Celsius and it is destroyed by necrosis.
Three month later, that tissue
is replaced by fibrous tissue.
The current guidelines, so the NCCN guideline say
the HIFU/cryotherapy is an option
for radiorecurrent prostate cancer,
but they are not recommended as
a primary therapy yet for local lives disease.
The AUA guideline, based on expert opinion mentioned
that focal ablation may be
considered in selected patients,
probably informed patient and we should
inform the patient that there's lack of
high-quality data comparing the outcome
with surgery or radiation.
EAU guideline set the high fuel cryotherapy
is to be used only in a clinical trial setting.
German guidelines approve it for
low-risk but not higher-risk cancer.
Now, there are several way that phototherapy can fail.
This is the slide I often show a patient when
I counsel them when we offer this to them.
How can focal therapy fail?
One is inadequate heat to a tumor,
so you have recurrent within the treatment.
Then inaccurate margin,
we tried to oblate 5-7 millimeter outside of the tumor,
but there's more extension beyond that,
we will have residual disease
in that area where we treat.
Then there's this fuel effect where other part of
the prostate that is not treated,
you can have new cancer or you have a progression of
GS6 and GS7, then inadequate staging.
If a patient has
metastatic disease at the time
of diagnosis and we don't know about
it and we offer this and we would miss the chance
of adequately treat that patient.
At UCSF, focal therapy has been
around for many years led by Dr. Shinohara.
This is outcome of
95 patient I have done over the years,
and with this immediate follow free survival was 96.
At two years follow-up,
three patient has metastasis.
Now the three patient that has metastasis.
When they read biopsy,
there's there's no cancer of the prostate,
but the patient had metastasis.
This is because the patient presented
with metastasis the first place, I think.
One patient has a salvage prostatectomy
of five and they want radiation.
There's a slight decline
in their sexual function over time,
there's no changes in the urinary function.
This is another study in the United States,
hopeless reasonably in Lancet Oncology
showing focal therapy using MI-guided of 100 men.
You can see a 24 month follow-up,
88 percent has no recurrent cancer that is significant.
Now, in terms of functional outcome in that study,
there is a slight decrease in
erection from 100-90 percent over the study period.
There's no patient with stress
urinary incontinence requiring to use a pad.
Only one patient has
a Grade 3 adverse event
that is a urinary tract infection.
One patient had a stricture that
resolved with a single dilation.
Now, if you look at a long-term follow up,
this is 600 patients with five years follow-up.
At five years, 88 percent has no recurrent,
and 98 percent has no metastasis,
100 percent is still alive at the focal ablation.
Two percent has urinary incontinence
that require the use of one pad.
Bowel complication was rare, only 0.3 percent.
If you look at a longer follow up,
this is a 15-years follow-up,
then you have more than 1,000 men,
132 men underwent salvage of the 1,000 men,
132 men undergo salvage
whole-gland or systematic treatment.
Three patients develop metastasis.
One of whom dies from prostate cancer.
A seven-years follow up,
68 percent has no recurrent for intermediate risk,
and high risk patient, seven years,
65 percent has no risk of recurrent.
No one died from
cancer at seven years and no one has metastasis.
The alkalotic outcome is very
promising at longer-term follow-up.
This is a 21-year-follow-up
of 674 patients undergoing whole-gland ablation.
As you see here,
a patient who had low or intermediate risk disease,
who opted for HIFU,
if you look here cancer PCa survival is
very good at 95 percent and
89 percent at 21 years follow-up.
For high-risk diseases its 65 percent so we don't
favor this applause for high-risk disease patients.
I think for future new research
is needed to improve recurring rate.
Currently at five years,
100 percent recurrent rate I think is too high.
I think we need to do more research to improve that.
I think using advanced technology will prove
it into selecting the appropriate patients for it.
The use of genomic and PSMA PET I think in
the future will be used more
widely to better select patient for this.
The use of MRI,
PSMA PET to guide ablation.
I think this will be the future here.
Also adjuvant and neoadjuvant setting the role
immunotherapy with the combination of focal therapy.
I think that could be an area research in the future.
What about an active surveillance?
You've heard a lot about
patient with active surveillance.
Focal therapy could be an option for the patient who
do not have access to active surveillance.
Or want to decrease the cost and the mobility or
repeated biopsies and PSA
check-up every three months or so.
It could be, we may be offering this
to select a patient with
low-risk disease or a patient
who had germline mutations or high risk,
high grade or adverse pathology
at the time of progression.
I'll give you an example of how we use
the latest technology to help decrease risk of recurrent.
This is a patient who is a 78-year-old gentleman.
We diagnosed Gleason seven cancer,
four three PSA of 11.
On the MRI there's
two areas that the PIRAD 5 here at the base,
and anterior base and there's a PIRAD 4 at the left base.
Now, this was biopsy.
This area turned out to be negative for cancer.
Here is a PSMA PET scan showing the area,
there's no cancer there.
Now there is a cancer here
that has detected four plus three.
You can see here is the left side, left mid gland.
We offer focal therapy
for this patient because it looks like
this cancer is only detected on
the apex left mid left base.
We would ablate the whole left gland.
However, I got a PET scan of
PSMA PET scan prior to the ablation.
You can see there's
an additional [inaudible] cancer out the anterior apex.
This will be too close to the urethra.
Imagine you will take this patient
and ablate half of his prostate.
You still have residual disease here.
This patient, I had told them would not be
an ideal candidate because of
the PSMA PET that show and cancer,
the apex that was not visible on
the MRI or the ultrasound.
Now, in the past, we would take
this patient to get focal therapy.
We would have a recurrent.
That's how we use PET imaging.
Here's a patient where we have detected
a lymph node metastasis for missing seven.
Rare but it can happen.
This is a male patient who had
additional foci cancer that was not detected on biopsy.
These are the ways that UCSF we'll be using.
Also we're also using
these genetic markers like our patient.
Patient who has higher genomic risk.
That is in the high-risk group.
I don't offer a focal therapy too.
For the take-home message,
I think focal therapy fills an existing gap between
active surveillance and whole gland therapy
, surgery or radiation.
It is associated with minimal side effects.
Study after study has shown this.
Up to your 80 percent,
90 percent of the patient
maintain their sexual function after
you're stressing continence is extremely low.
There is promising oncologic data after
15 and 20 years follow-up and
new research is needed to reduce recurrent risks.
Ultimately the success of
focal therapy depends on the patient's selection.
Life long surveillance the patient has to agree to.
Also, we need to use high-quality MRIs and targeted
biopsy and perhaps use of genomic and
PSMA PET just like this patient for this therapy.
I like to end with acknowledge from Dr. Carroll.
He's the one that told me to
do a revamp of focal therapy program
two years ago and now he would
refer a lot of patients to us for focal therapy.
We've done over the last year,
100 patient now and Dr. Shinohara has
been the champion of focal therapy for many, many years.
Dr. Crocitto is the one that bought us
the high focal machine and
the rest of my colleagues in the department.
Thank you [MUSIC]