ASK ME ANYTHING

Uh, so I want to welcome you all for

being here. Uh, my name is Mark Maguire.

Uh, as you know, Aaron has been carrying

the load on this thing for over five

years. And, uh, and he has a family. He

has a daughter. So he's asked for some

help and and the the good of value of

God here out of this organization. I

said, "Yeah, I'll do what I can." And so

and he takes a bunch of roles. So

there's a couple other folks that have

been helping with facilitators, Mike

McCiri and Martin Miles. And I don't see

Mike here.

Oh, is this Mike walked? Oh, hey dude.

How you doing?

Yeah, I hope so.

>> And all right, thank you. Thank you. So,

quick reminder, Stanford Burham letting

us use this. It's just for free. It's

just a very, very great gift. And so,

one of the things they're real strict

about is there's no water or food in

here. Um, and so we honor their wishes.

So, I appreciate if you keep in mind on

that. When it comes to lunch, it's kind

of there's a few tables, but it's mainly

sta stand and talk and meet someone

while you're out here. Okay. Now, let

let me introduce some of the principles.

Here we go. Okay. Aaron, director. Uh,

and then we've got Jean is another

director, Bill Manning. John's

treasurer, Steve Secretary Newsletter,

which is just a fabulous job. and Bill's

out there uh with the library and over

900 members. It's fabulous. We actually

got a question in from Michigan for this

event. Uh so, and we're growing. The

other thing, folks, is

I I think we could spread the word. I

mean, I think a lot of us are here

because we didn't know anything about

prostate cancer. Next thing we're gleon

7,89

and uh if I wish I would have known

more. But so talk to other men that you

know and people you care about, work in

other places. I think we can drop it

down from one out of every eight. It

shouldn't be that many people getting

cancer. That catch us early like most of

you all know it's 99% curable. Um

so first thing we're going to do is a

quick survey and I think it's important

on this. So, um, anyone here is recently

diagnosed,

uh, for prostate cancer? All right. All

right. All right. I just really hope I

think you'll be helped here. Then, um,

anyone to four years.

All righty. And then we got 5 to 10

and then 11 to 15.

And there's anyone longer than 15.

So the very important thing of that is

it's a disease we can manage now if we

keep up with the treatments and and rock

stars like Dr. McCay coming in we can

manage this. So it's it's a shadow. I

mean we all know but we can manage it.

So then uh the next is on some of the

different treatments. So, uh, uh, anyone

on active surveillance, okay, good few

of the and it that's come a long way.

Surgery

with you on that. Radiation

and hormone

and any chemo.

All right. And um so when you see the

people with their hands up and maybe

you've started with a surgery, there's

been a return, there might be need for

radiation or hormone, talk to some of

the people in the room because they've

they've walked through this and they can

tell you their experiences

and um so another thing that's coming up

Vanna and

this uh this this prostate cancer

support group. Uh you can YouTube to see

some of these present. They're all on

there. And so when you're looking

through and you're coming through a next

phase in your treatment, go back because

there's highly likelihood whatever phase

of treatment you're going through, we

have it on the website and just getting

a knowledge to be your own CEO of your

health. Um, and they're posted on

YouTube. Uh, prostate cancer support on

the YouTube app. You find the logo and

you get this stuff. There's a lot.

There's also a hotline and um um and

there's, you know, looking for

volunteers to help on that. And

sometimes,

uh, you know, it's it's helpful. It's

sometimes this can be overwhelming and a

hotline or new to information. All

right. So then we have a meeting on

April 22nd. This is going to our future.

What we're trying to do is the

organization is growing is gather more

individuals to help steer this and and

help with the different processes. This

is nonprofit. No one's getting paid.

There's so many people do so much work.

And Aaron has carried this fabulous. But

it's it's it's time. the more we get

involved, the more we learn, the better

we can address everyone's questions and

concerns. Uh, so April 22nd at uh 10

a.m. in Carmel Valley, we're have a

steering committee. Just show up if

something you can help with or say,

"Nah, it's not me." But it'd be great. I

think we all feel rewarded when we give

back. Um, and like said, we're our own

case manager. Um, so the more you can

understand about this disease and the

better educated

and the better you are as a CEO, the

better questions you can ask with your

physician and uh and the physician

you're you know you're you're running

through those pretty quick. So the more

you can make a background and a and uh

questions the better you can be as a

CEO. Now, we're not we're just

experienced participants and this is

very very important. We're not medical

professionals.

We're on the other side. We've gone

through this. So, we can get advice what

of our experience is, but the deal is to

get as much information so you go to

your trusted physician and that's where

you get your treatment advice. We can

give you this is what surgery did with

me. This is what hormone therapy is

still doing with me and and things like

that. So that's where it can help.

So it's a 5013 donations tax available

and it helps. I mean all this is out of

pocket. No grants. And so we got a

couple baskets here. I'll start it out.

Eric

and u so if you can help out. We just

want to cover the costs. No one's

getting rich. and uh and uh so next

month what's happening

um this is prostate cancer research

institute so they have a virtual

conference and this is cutting edge

stuff what they're coming out with so uh

there's the information

and it's just amazing what's coming up

and for me when I look at some of the

future cures

and treatments coming up. It's kind of

like the carrot that when I kind of get

pity on myself, wait a minute, there's

stuff coming down the road. My hormone

my the hormone therapy is working. So I

think it's good for us for our own

mental health too to understand these

things that are coming up. Um this other

uh next month is going to be really

interesting. It's focal treatment using

which I'll try to say this correct.

Ireversible electroportation.

Okay.

All right. So, what this is is a

minimally invasive non-therrmal

technique. It uses high voltage and

short pulse electric current to blast

cancer cells. So, there's so many new

things coming out. It's not just the

knife. It's not just poop loads of

radiation. So, there's stuff coming out.

And when you hear these things, those

are great questions to share with your

your medical professional. And sometimes

it takes a while for this information

get disseminated down to their clinic

and to them. Um, now,

uh, Dr. McCay,

I when if you ever been to the January

thing with UCSD, she's front and center.

She's meeting with people. uh she's so

dedicated and so knowledgeable. We it's

a real blessing that uh she's here with

us today. So she's professor of

medicine, urology, radiation medication.

There's a better name I can't say. And

and also director of co of clinical

studies sciences and co-leader of oh

genology

>> oncology. Thank you. at Morris Cancer

Center. I used to be able to lift heavy

things. And so we're in a treat for

today. It's ask anything. So think of

your questions.

Um

and this is the stuff that gives you

confidence, gives you knowledge because

sometimes you feel like you're not in

control when you hear the C-word. And

and we can be in some control on this.

And this is this is a great opportunity.

and uh as a medical oncologist at UCSD

Health, she specialized. She also treats

people. There's several individuals in

this room that she's she's their

oncologist as Yeah. Oh, yeah. Let's lift

hands. How many people are being

treated? Look at this.

So, so she not only is out front looking

at clinical studies and she I'm making

an assumption here, but when she's

working hands-on with people, she knows

what clinical studies resonate with us.

So, she's in touch and then she's out in

front with clinical studies. rockstar

and uh uh so and her her uh been root

works been appeared in peer-reviewed

publications such as New England Journal

of Medic uh medic medicine sorry Journal

of Clinical Oncology and many more and

like I said she's not only recognized

her peer recognize us and so

what we have now

is Dr. McKay, please take her away.

Thank you so much for me.

>> Sorry.

>> Okay.

>> Well, it's a real real pleasure to be

here with you all and and uh in chatting

with Aaron and actually some of you all

in the room, we thought that instead of

doing a formal presentation that we

would actually just open it up for

questions because every time we come and

do a presentation, there's never enough

time to get all of your questions

answered. So, I'm happy to actually open

it up for you all to come to the mic and

and ask questions. Um, and the other

thing that I will say is um, and I know

Mark may have touched on this a little

bit, this is not intended to provide a

consultation about specific things that

are kind of going on with you because,

you know, if you only have one piece of

the pie, you can't really make an

informed decision about what to do or

how to advise somebody. So, of course,

we're happy to see patients in the

clinic and do a very comprehensive

assessment, but it it you really I would

be doing you a great disservice if I

didn't have the totality of your medical

history and making recommendations

around what to do next. Okay.

>> Yes. Thank you.

>> Yeah.

>> So, we're ready.

Okay. Here we'll go next. Ben, you're

saying goes away quick.

>> Good morning, doctor. Uh, thank you for

doing the prostate cancer summit every

year. That's really a great event. Um,

my question involves um the needle

biopsy.

>> Um,

speaking from experience, they're very

uncomfortable

and I was wondering if there are any

viable alter alternatives to a needle

biopsy.

>> Very good question. So there are tools

that can be utilized to assess the risk

of having a clinically significant

prostate cancer at the time of biopsy

that could be utilized around making a

decision whether to actually undergo a

biopsy. So there are urine based tests

um that basically look at different

signatures to see what's the likelihood

that there's going to be a bad cancer

there. Um there's MRI as well but the

diagno honestly the diagnosis of any

malignancy with the exception of a

hpatic cellular carcinoma is made

hytoologically

meaning you look at the tissue under the

microscope and make a diagnosis. But

there are tests that could be done to

assess the likelihood of a high-risk

cancer or clinically significant cancer.

And all of these prediction tests,

they're never 100%, right? There's it's

going to give you a risk. And so the

probability that there's a clinically

significant cancer is 10%, 20%, 50%, 5%.

That risk for any specific individual

may have a different meaning, right?

Like for for a 40year-old,

a 10% risk of a clinically significant

cancer is too high. For a 85year-old, a

10% risk of a clinically significant

cancer is I'm not going to deal with

that. That's okay. It's not a big deal.

So, the risk also is interpreted

differently based off of your unique

situation.

>> Yeah.

>> There you go.

>> Uh, good morning. Um,

if the cancer was just by itself, that

would actually be pretty easy. But

sometimes we have other parts of our

bodies that are falling apart at the

same time. And so, one of the things I'm

curious about and I've been reading a

lot about is the use of supplements like

uroliththna and protein supplements and

amino acid supplements to support muscle

recovery. specifically if you have like

other surgeries or other things going on

at the same time that you're having um

prostate or ADT treatments. I'm

wondering if you have any kind of

thoughts about that in general.

>> Yeah, honestly I think in general as

people are aging ensuring that they're

that they intake an adequate amount of

protein is a real important factor. Most

people are protein deficient. You don't

have to get your protein from animal

sources. There are a lot of non-animal

sources where you get protein from. But

actually a proteinrich diet and plant

forwardbased diet is critical for health

and longevity independent of prostate

cancer. So I actually am fully

supportive of you know uh you know

enhanced protein intake. Now, do you

need to be taking a supplement? Do you

need to be taking ancillary pills?

This is my bias. I'm more of a it's

better for you to get it from your food

and from the natural sources than get it

from a pill or other um formulation.

Now, if you know somebody is has an

allergy or a deficiency or something

that needs to be supplemented,

absolutely. But I think getting these

nutrients from your food is the most

important thing. If we look at the world

and there are these blue pockets on

earth where the life expectancy is crazy

high like 90 100 years.

Those places do not include people who

are heavy loading on supplements.

They're eating from the earth. They have

a very plantforward diet. They have some

animal intake. A lot of it tends to be

fish. Um, you know, not so much gamey

kind of animals and it's more uh, you

know, it's it's not with extensive

supplementation,

you know.

>> Who's next? Come on. Right here.

>> Um, thank you for being here. I I had my

prostate out in 2002, okay? 24 years

ago. But there was still a PSA and so

they did some radiation, but there was

still a PSA. And so with Kaiser, I was

and there used to be a bunch of people

here from Kaiser. We met and we they

gave us drugs to get rid of our

testosterone and that stopped working.

Okay. So then they put me on another

pill, Excandi. Okay. And you gave me

great advice because I was worried about

the ecstandi affecting my neuropathy and

you said well you don't have to take

four pills you can just take two and

that worked perfectly and so now for a

couple months I take the extandandy my

PSA goes down I stop and four or five

months later I start again now here's my

question is there lately some better

drug that might work for for me.

>> So very good question. So I will say

there are three FDA approved

anti-androgens

that block the action of testosterone.

So Ecstandi or Enzolutamide is one of

those drugs. It's what we call an

androgen receptor antagonist. It binds

to the androgen receptor to prevent

testosterone from binding and that

basically prevents the androgen receptor

from working. There's a total of three

drugs that are antagonists.

Derolutamide is another one or NCAA. Um,

Appalutamide is another one. There's

probably more similarities than there

are differences among these three drugs,

but each of these three drugs has a very

distinct um drug drug interaction

profile and distinct side effect

profile. There's a couple of nuance

differences between these agents.

Derolutamide is the newest kit on the

block. Um there's no difference in

efficacy from Ecstandi, but in some

people who have an intolerance to

extendi, they could potentially tolerate

derolutamide a little bit better.

Derolutamide does not cross the bloodb

brain barrier as much as extandandy or

enzolutamide and and applutamide do. And

so it tends to not cause as much, you

know, fatigue, falls, those sorts of

things. Now, there are other types of

hormonal agents that are being developed

that are in clinical trial testing that

if a drug like Excandi were to stop

working can be considered. And they are

um I think we've we've touched on them

previously in one of my talks to you all

about novel therapies. They are AR

degraders or sort of next generation

um what we call SIP 11 inhibitors. You

all may be familiar with Aberatarone.

Aberatarone or Zaitiga is the other name

for it. Um it prevents testosterone

production in the adrenal gland and

works on a certain enzyme in the adrenal

gland. There are drugs that kind of are

kind of like a souped-up version of of

Zaitika. So there are things coming.

Well, and I'm 82, but I have to say I

don't have testosterone anymore when

they test me. So, but basically, you're

saying Extandi is okay, right?

>> Exci

tolerating the Extandi even at the two

pills. There are other drugs like

Extandi that may be tried if you're

intolerant to Excandi.

>> And what's the best one? I'm having

trouble remembering. I'm sorry. I

wouldn't say that there's a best one.

They're just different. So deralutamide

is one of them and applutamide is

another one.

>> Abolutamide.

>> Appalomide. Yeah.

>> Thanks.

>> Thank you.

>> Thank you. Here you go.

>> Thank you. Appreciate it. I Dr. Mccay.

Hi. I'm new in the journey. I'm barely a

year almost a year today. And in past

conferences when I've chatted with other

guys out in the hallway there during

lunch, I was stunned at the amount of

guys who have had recurrences.

Do you envision as the treatments as we

get more research and the treatments get

better that there'll be less

reoccurrences in the future?

>> Yeah, I first off I'll say

>> thank you. There's probably a selection

bias with the circles that you're

talking to because people who have their

cancer bected and their PSA is

undetected, they're done. They're

they're not engaged. They're not plugged

into a support group. They're they're

not even thinking about their prostate

cancer. So the the majority um the bulk

of people who are diagnosed are actually

either have a cancer that doesn't need

to be treated

um or receive definitive therapy and are

cured. Now that being said, there's been

a lot of mixed messaging um to primary

care and to the general medical

community community about prostate

cancer screening. And it's that's been

um a result of guidelines by the

preventative services task force

actually against prostate cancer

screening. So I think we backpedalled in

around 2012 where prostate cancer

screening was basically giving given a

recommendation D meaning don't screen.

So um that has since evolved. that's now

been given a C designation, meaning talk

about it with your doctor and then, you

know, order it. But it it's there's a

lot of mixed messaging to the general

like just PCP primary care community

about who do I need to test? Like should

I be testing for PSA? So, we actually

have seen what we call stage migration.

Um, you know, in the late 2000s and the

1990s, we were diagnosing a ton of just

low-risisk prostate cancer and stage

one, early stage prostate cancer with

everybody was getting tested. Everybody

was getting treated and we probably did

a disservice to many because there was

probably people that never needed

anything done for their prostate cancer,

but we didn't know any better then. And

so because of that, there was this

recommendation against testing. But what

we've seen now is because now we've

stopped screening to the extent that we

had been. We're seeing more people

diagnosed with higher stage disease.

We're seeing more people diagnosed with

metastatic disease. And now because we

have PSMA PET imaging which has enhanced

our ability to detect disease, we're

catching things earlier and diagnosing

people with a higher stage earlier on.

So that I think it's a combination of

those elements of why

there may be this feeling that gosh

everybody's recurring. Okay.

>> It's a big statistic.

>> Yeah.

>> Uh thank you for being here. I'm just

wondering are there any advances or

applications of immune therapy for those

who may have disseminated prostate

cancer?

>> Yeah. And number two, uh, what PSA level

do you feel that these therapies should

be initiated, be they anti-androgen or

otherwise?

>> Uh, so great questions. I'm going to

tackle the first one. The second one is

is, uh, we'll talk about it. So the

first one about imunotherapy.

Um, there are novel forms of

imunotherapy that are now in late stage

testing, phase three testing for

prostate cancer. Historically the

classic drugs the PD1 PDL1 inhibitors

that you may have heard of like

Nvolamab, Pembberloab or other

commercial names for these agents are

Kruda or Opivo. You may have heard of

these drugs. They historically by

themselves in an unselected population

have done nothing. They have not really

been effective. But there are new

classes of drugs called TE-C cell

engagers. And these are a type of

imunotherapy, but you can almost think

of them like targeted imunotherapy. So a

TE-C cell engager binds to a specific

protein that's on the cell surface of a

cell of a tumor cell and also binds to a

T-C cell. So it brings the TE-C cell in

close proximity to the tumor cell and by

doing that the TE-C cell the cytotoxic

T- cell can do what it's supposed to do

against the foreign body and in the

first iteration of these drugs they were

actually quite

>> there we go okay here they were actually

quite toxic um because they

overactivated the immune system they

were initially developed as pretty small

molecules so you almost had to give them

as a continuous infusion but the field

over the last decade has evolved and now

many of these drugs um can be given

intravenously

um you know whether it's on a 3-w week

or six week basis one of the drugs is

you know given totally as an outpatient

um and these are in phase three testing

so I think that I'm actually super

excited about the T- cell engagers I

think um they're first probably going to

make a headway in hormone resistant

disease but the hope is that they will

move up um to metastatic hormone

sensitive and even to biochemically

recurrent and localized disease. Now the

the other question around at what level

PSA would you start androgen therapy? I

couldn't even begin to answer that

question. Um it is so nuanced and there

are so many different in what context

localized disease postradiation

postsurgery biochemically recurrent um

you know metastatic castration resistant

so it is it is uh an unanswerable

question but I what I will say is it's

never just the absolute value of one PSA

reading at one time when we make a

decision again around who should be

treated with But it's looking at

everything that's going on with that

individual patient independent of their

prostate cancer. Whether coorbidities

they have, what other drugs are they on?

What's going on with with the patient?

What are their disease factors? You

know, where is their cancer? What do we

what's their gleon score? What molecular

features around their cancer inform how

aggressive or not aggressive it's going

to be. It's looking at the kinetics of

the PSA. And yes, we look at the

absolute value of the PSA, but that is

only one marker of like 20 markers that

are looked at to make a decision again

for starting something or doing

something.

>> I think this gentleman's first. We'll

get you next.

>> Thank you.

>> I came here with many questions on my

mind, but I don't think we have time for

all of them. But since you mentioned

protein deficiency, I have a question

about that. And you said uh it's pretty

much that the senior population is prone

to protein deficiency. Am I correct?

>> Yeah. I think as we as people get older,

they're just not consuming as much

protein can be at risk.

>> And that's why I'm asking this question

because I am a senior citizen

>> and uh I am advanced uh with prostate

cancer on androgen deprivation and uh I

do what I'm supposed to do. I eat very

well and I exercise every day. And

because I am so

uh deficient in testosterone, I can't

build any lean body mass no matter what

how much protein I take, how much

exercise I do. So my question is, is it

really that important? Because he can

only metabolize so much protein and uh

eventually

uh the nutrition is feeding the cancer

cells. Uh, I don't know if that's my

question or not.

>> So, first I will say the protein that

you eat is not feeding your cancer

cells. So, dissociate those two.

>> That took one worry off my mind.

>> Okay, that is not a true statement.

>> Well, I Yeah, that wasn't my question.

But my question is the fact that I do

everything. Is there any way that I can

even expect to build any lean body mass

because it's impossible?

>> Yeah. So my answer to that question for

for anybody of any age is there's what

we think in our mind we're doing and

there's the reality of what in fact

we're doing. And if if your goal is to

build lean body mass, you can do it and

you can do it on hormone therapy. But it

takes work. It is hard to do. It

requires resistance training. It

requires loading resistance exercise. It

requires

really doing a deep d like actually

calculating how much protein you should

be taking in if you intend to bulk.

There's a methodology for this and how

much you know are you actually in fact

taking that amount of protein load.

>> You're eliminating the pain factor.

So that's what I'm saying like it is not

something that cannot be done but it is

hard to do and it doesn't have it

doesn't mean you need to go in the gym

and be like pumping a lot of iron and

doing all this stuff but if that was

actually your goal you can achieve it

with a dedicated nutritional physical

therapy plan it can be done

>> and supplementation is that

>> does it does it need to be in the

formula

you can still build muscle with a low

tea state. It's harder to do, but you

can still do it.

Huh?

>> You can. You can. It is harder to do. It

is It's It's like a science. It's like a

mathematical formula like honestly.

But it's hard. That's why when

>> my life expects

>> so if we're thinking about that's a

that's a different question but there

are actually

methods like if if you read books on

longevity

there are certain things that if you

want to live to 90 you need to be

capable of doing these things at 80. If

you want to live to 80 you need to be

capable of doing these things at 70. A

lot of the things are opposite of what

you think that they are. It's it's can

you just walk up and down like you know

the street

carrying your body weight in a backpack?

Can you do that? Can you walk? Can you

just hang on a pull-up bar and just hang

No, you don't even need to do a pull-up.

Can Can you hang off of the pull-up bar

for a minute?

>> Correct. Without this. These are sort of

things like like these sorts of

maneuvers that uh allow you to be

functional as you get older. Like your

pelvic girdle should be super strong,

right? Like you need your quads, you

need your butt, you need your glutes,

you need your hamstrings to get up out

of a chair, to get off the toilet, to

get out of the car. You sit at

somebody's house, you go, you're having

dinner, they've got a low couch, you sit

on the couch. you get up off that couch,

there's no there's no handrails there.

>> Right? So, these are the things like

when when people are exercising, I'm

like, you need to do functional

exercises that are going to help you be

a stronger version of yourself. Um,

you're in the cupboard, you're in the

kitchen, you have to take a heavy glass

from the cupboard. So, are you able to

do that? Are you able to take a weight

and pull it down? The microwave is up

top. You put a plate. Are you able to

pull it out? So, when you're in the gym

exercising, these are the things to be

thinking about. I want to work out my

shoulder girl so I can do this activity.

I want to work my quads out so I can get

like it's not just for aesthetic

purposes. It's like functional

exercises, you know.

>> Yeah.

>> You don't really know how much protein

you can ingest. And anything I ingest is

always going to fat tissue no matter how

much. And I'm always hungry and I have

to limit that. But should I be focusing

on limiting everything but protein?

>> No. So I think you it sounds like I

think people can benefit from meeting

with a nutritionist and calculating

how much macros they need to be eating.

The three macros are protein, carbs, and

fats. And it's like a simple formula

like how much of those three macros I

should be eating. and how many cal if

your intention is to gain weight and

gain protein mass there's a formula for

like literally a formula for doing that

like this is how much calories you need

to take in and of those calories this is

how much should be protein and this is

the time of day you should be eating

those things

>> discipline

>> it is it's hard that's why like the bulk

of the like there's only like you know

5% of the population that actually is in

the standard dev of like having lean

body mass where they're like, yeah, if

you look at the percentage of people

that had a have lean body mass, less

than 10 20% or less than 15% for a man.

It's 5% of the population, if that.

You're you're it's easier to be there's

more people that are millionaires than

in the category of less than 15% body

fat.

>> Seriously, a millionaire,

>> huh?

>> I'm happy to be a millionaire.

>> I'm just saying. I'm just saying it's

hard to do. It's easier to do be a

millionaire than to be have lean body

mass.

>> Yeah.

>> Uhhuh.

>> Hi again, Dr. McKay. Uh, the androgen

receptors have been a major target for

drug therapies for a long time. Are

there any new targets that seem very

promising to you for some groups of

patients? And what's the status of

research on treatments using those

targets? Does this research involve new

or existing drugs? Yeah, very good

question. So, I think there's been a a

lot of enthusiasm

around targeting the surfome of any

cancer. On the surface of any cancer,

there are a lot of protein um receptors

that kind of hang out on the surface and

many of these proteins have a

predelection to only be on the cancer

cell and have limited expression in

normal tissue. And so there's been a

resurgence of attempting to

uh target those receptors. There's many

of them in prostate cancer. Steep one,

steep 2, KLK2,

um B7H3,

there's a ton of them. And the drugs are

getting more refined because there's

lots of ways we can target those

receptors. we can target those receptors

with um a radio conjugate where you can

have a a small protein that targets the

protein on the cell surface and it has a

linker and then there's a little

radiation molecule. You can do the same

thing with chemo. Again, there's a small

molecule or antibbody that binds to

what's on the cell surface, a linker

that's linked to chemo that gets

delivered right to the cell. The T- cell

engagers I talked to you about also same

modality. they target something on the

cell surface linker and then um or not

there is kind of a linker and then the

targets the immune cell. So that concept

these are all some of these gene some of

these cell service targets are andigen

regulated some are not necessarily

androgen regulated like for

neuroendocrine tumors um there's a

protein called DLL3 that has been um

there's been a lot of enthusiasm around

targeting that that's a non-andigen

regulated protein.

Yeah.

>> All right. Hang on back here. Here you

go partner. You're getting your miles in

here, your steps in up and down.

>> Y

it's probably Well, could you speak or

address the um what what I understand to

be a masking of PSA

on finasteride?

Finestide.

>> Yes. So finasteride

is a five alpha reductase inhibitor.

Five alpha reductase is required to it

it what it does is convert testosterone

to DHT. I know there's been a lot of

talk about testosterone and everybody's

fixated on testosterone. DHT is actually

the most potent androgen in your body.

It is more potent as an androgen than

testosterone is. But many people just

think of testosterone. So by blocking

the conversion of testosterone to DHT,

you actually end up having lower levels

of DHT

and and which is a stronger androgen and

that's how PSA goes down. But all of

that is just um there's not like a um

therapeutic benefit of that because if

you block at DHT,

what ends up happening is you build up

testosterone, right? Like if you have if

you have a highway and you block the

highway, you're not riding on the

highway on the other side of the

blockage, but where there's a blockage,

anything prior to that is building up.

So you have T going to DHT. You block

that path. DHT goes down. It's a more

potent androgen. So the PSA goes down,

but you actually have more tea.

>> Is there any advantage between

finasteride and uh uh flax.

>> So different drugs. Uh PHMAX is a uh

alpha blocker. It literally just works

at the receptor. The finasteride

does modulate the hormonal access by

dropping down DHT and having less of a

more potent androgen.

The prostate gland itself shrinks down.

So sometimes finasteride is used to help

with urinary symptoms. Um if people have

BPH um but it's not used as a

therapeutic in prostate cancer.

>> But as far as the BPH, I mean one better

than the other.

No, one one's not necessarily better

than the other. They're just different.

I think in men who have prostate cancer,

there's probably

like a desire to not use finasteride

because it can um kind of again mask the

PSA level. Okay.

>> Which is where I got caught. I was

watching my PSA annually and

every uh primary care and FAA doctor I

went to, nobody wanted to do a digital

exam

>> because it wasn't recommended anymore or

it wasn't recommended 69 years ago. So

I'm watching my PSA hanging around 3.5.

I see your first test results and in

parenthesis behind the PSA says masked

by finestide

actual PSA something like 7.5.

I think the general population at least

I'm guessing uh watches their PSA and if

they're taking finasteride they're in

for a crash course and what we're doing

right now.

>> No, totally. And in actuality um we have

a lot of issues with the way PSA is

reported in our lab, right? like it's

it's um

you know they they flag it as being as

being abnormal at a level of four but

there's it's totally skewy you know um

because a level of four for like a

40-year-old is grossly abnormal and a

level of four for an 85year-old is

probably okay and they don't take into

account the finasteride piece they don't

take into account you know the surgery

piece whatever piece so it's almost

better for them to not even say what is

normal and abnormal

and just give the level. Um, but then

again, you're like, you know, if you

want to speak to the primary care doctor

who's like doing a bajillion things,

they need a flag. So, there's this

constant balancing act with the lab of

like, how do we better report or put

these things in like, you know? Yeah,

>> I'm up. Um

I I have a question about effective

non-ADT strategies for someone who has

Parkinson's and reoccurrence.

>> Very good question. So, um I'm I'm going

to take a step back and when I say ADT,

I'm going to break it down into

um

strategies that drop testosterone

um or that are I should say like

castrating strategies versus

non-castrating strategies.

Under the non-castrating strategies, if

there are concerns about actually having

somebody on ADT,

an anti-andigen by itself can be used.

So a drug like enzolutamide,

derolutamide, appleide, bolutamide, all

of those amides, they're all

anti-androgens. They block testosterone

from binding to the receptor, but they

don't actually um drop tea. In

actuality, your tea levels go up on

those drugs if you were not given some

other medicine to drop tea. So those

those strategies are noncastrating

strategies.

When we talk about um other ADT

strategies that will in fact drop tea,

the most common is a G&R

agonist. Something like Lupron,

Trellstar, Lupralide, Eligard. You may

have been been familiar with those. They

actually block a certain hormone in the

brain that tells the test the testicles

to stop making testosterone. There's

another form instead of an agonist

um that's an antagonist. And some may

say, well, how is it that an agonist and

an antagonist can both drop tea? Well,

the agonists the way that they work is

by continuously blocking by continuously

activating the receptor, it actually

turns it on. So is normal physiology

like normal just you know human living

the receptor in the brain the G&R

receptor is not always on. It's on in a

pulsatile way. It's on a little bit then

it's off. It's on a little bit then it's

off. It's on a little bit then it's off.

If you just keep it on, it's like if you

just keep it on, it will turn off on its

own. And that's how most agonists work.

By by a constant yes signal, it turns it

off. It's like the batteries run out.

Even though it's constantly on the

antagonist,

they just turn it off right away. There

isn't this turn it on, then turn it off,

they just turn it off. There's been, I

know, some enthusiasm in different

circles around estrogen and a resurgence

of estrogen therapy. Estrogen therapy is

castrating therapy. And again, it works

by a negative feedback loop on the

brain. If you give estrogen,

the estrogen that estrogen in the body,

there's a conversion of testosterone to

estrogen. If you give estrogen in a

continuous way, it's going to turn the

signal back to the brain to say, "Stop

making testosterone. Stop making

estrogen. I got too much estrogen. Stop

making estrogen." And in a man, the way

estrogen is made is testosterone

converts to estrogen in the periphery.

So estrogen therapy, like through a

patch, we don't really do pills or gel,

is actually castrating. it will drop

your testosterone levels down and they

will get very low to the very low level.

So for somebody who desires a

non-castrating strategy,

I would say it's the anti-androgens

without one of these other three classes

that I told you about.

Hopefully I didn't confuse you.

It's very complicated. I think there's a

lot that's out there and people will

will see snippets of things but you

really actually have to understand the

biology and mech mechanistically what's

happening. So it's hard to categorize or

nonj what the side effects deteriorating

side effects might be on muscle mass or

>> so with non-castrating therapy the

anti-androgens I think there's probably

a less and there and with with their use

without ADT there's a less negative

effect on the bones there's a less

negative effect on the muscle where you

run into trouble with those drugs is um

because they actually increase

testosterone you actually have more

estrogen and people can be at risk of

developing breast tenderness or breast

enlargement with those sorts of drugs.

Sometimes the hot flashes can also be

worse. Um so it's kind of a trade-off um

of what you know it's like pick your

poison what what can you tolerate more

or less of?

>> Yes. So I have a question that's more

basic about the nature of cell of cancer

cells that are hormone sensitive

>> and currently in a state of can you say

um slumber or

>> uh are the cells capable of

uh mutating in that state and can they

just sort of die a natural death if

you've you've deprived them of anything

to eat for say three or four years.

>> So very good question. We have not been

able to

get rid of every single last cell in

prostate cancer with any sort of

systemic therapy.

So if we if you have an individual who's

who doesn't, you know, if their disease

is um only being treated with

systemic treatments, not surgery, not

radiation, not an attempt to take away

all visible sites of disease. The

systemic therapy is non-curative. It's

it's hard to kill every single last

cell. that doesn't mean that somebody's

going to die of prostate cancer um

because there's a lot of other things

competing for um your wellness um as

people get older but there's um you know

it's hard to kill every single last

cell. Now there is this state as you

describe of dormcancy where the cell

gets into this dormant state. First off,

I'll say that you're probably killing

off a ton of cells. But what I'm saying

is, do you kill every single last final

cell?

And hormone therapy is effective. It

does cause cell death to some cells, but

there are probably some cells that do

not die from hormone therapy that enter

into a dormant state. And there's a lot

of research that's actually being done

on how to induce dormcancy and what

triggers a cell to get out of being

dormant. And it could be a slew of many

things. I think it's a immunologic and

molecular event. I think that the cell

can acquire mutations. I think the

immune system can impose different

selective pressures. the world that

we're living in, what you're taking in

in your body, your environmental millu

can, you know, uh induce certain

pressures that cause a cell to get out

of dormcancy. But there's a lot of

research to be done on that because if

you can keep a cell, if you have a drug

that targets maintaining a cell in a

state of dormcancy or preventing it from

exiting dormcancy, that could be a very

effective drug, right?

Yeah.

Dr. McKay, thank you for uh thank you

for being here. I have a two-part

question.

>> Oh, there we are. Okay, I'm sorry. Right

here.

>> Sorry.

>> Uh two-part question. Uh and some of

this may sound familiar. We discussed

this a little bit uh back at the

conference uh back in January. Uh

relates to uh uh postp prostatectomy

uh biochemical recurrence. And you know

today the standard of treatment is

salvage radiation which to me feels like

hitting a small nail with a large

sledgehammer. Uh you know and you know

potentially significant side effects for

that. uh have been watching uh with

great interest the advances that are

being made in targeted therapies,

immunotherapy,

uh uh PSMA, theronostics, but those

treatments are not really applicable to

someone who is just uh getting over the

threshold of the point where treatment

is probably something that would be

advised.

>> So my first part of my question is where

do you see the technology going? Are

there going to be alternatives to

radiotherapy for those uh those

circumstances emerging in the relative

near term? And the second part of my

question is among the radiotherapies

available, what's your p perspective on

proton therapy versus uh more

conventional radiation.

>> Okay, very very uh good question. And so

the first I will say is um there are a

lot of treatments that are being uh

designed and developed that I think

could have legs.

Your question is actually around

how do we design a trial with a

benchmark

that regulatory authorities will approve

to allow those treatments to enter into

that early state. So the state of

biochemical recurrent disease is a very

very difficult state to conduct clinical

trials in and to conduct trinical trials

that ultimately will result in a

meaningful

outcome for a large group of people that

will allow regulatory authorities to

approve a drug because this is a state

where you feel good. You don't have side

effects. There's nothing on your

imaging. It's just a PSA rise and if we

want to introduce a therapy in that

space,

you know, from the the standpoint of the

regulatory authorities and probably also

for patients as well, you have to prove

that that therapy is either going to

delay metastases or it's going to make

somebody live longer.

So to design a trial and now we have

PSMA PET imaging which the benchmark for

developing metastasizes isn't metastases

on PSMA PET because in the eyes of the

FDA if you detect a little bit of

something in a rib somewhere is that a

clinically significant thing is is it

clinically significant

is that going to impact somebody's

overall survival so what if I detected

it in a little rib at this we have to

prove to them that it matters.

We haven't yet proven to them that it

matters. Um so and the way that we prove

to them that it matters is like every

single study that we do needs to embed

serial PSMA imaging and we and that's

very costly.

We not to say we can't afford it like

that's like an incredibly costly thing

to do in a context of a trial for a

thousand patients to do serial PET scans

that's covered by who whatever pharma

company's running that trial. They've

been very resistant to doing that. They

should, but they've been resistant. So,

where I'm getting at is yes, there are a

lot of effective therapies that I think

definitely have legs in this space, but

it's a product of the way we design

trials and a product of like how do we

introduce a therapy in that manner and

and design a trial that's going to

result in some sort of clinically

meaningful thing. So in the in the again

in the eyes of the FDA, a therapy that

just makes your PSA go down, it's not

going to result in that drug getting

approved.

And for most scenarios, many drugs that

may just delay the time to progression,

but not necessarily make people live

longer. That may it's not a guarantee

that a drug like that's going to get FDA

approved. So this is why there's like a

lot of stakeholders in the game for drug

development because it's it's patients

standing up and saying no, this is what

matters for me. No, I I care about that.

Like that's a meaningful thing to me. Um

it's it's physicians, it's

investigators, and it's the regulatory

authorities. With regards to um the

point about radiation therapy and

salvage radiation therapy, I get it. I

get this whole like but I don't see it

and I'm just going to radiate this field

and I don't see it. And the whole

concept of salvage radiation is that

there's a high likelihood that there is

microscopic disease in the pelvis. And

if we adequately treat the prostate or

prostate bed and the nodes in this area,

we're actually going to kill those cells

that would otherwise have the potential

to spread. And you almost don't want it

to be so targeted. Like you do, but you

kind of don't because you don't know

where the cells are, but you have a high

index of suspicion of where they

actually are in that they could be in

this region. And so salvage radiation

therapy is a curative option. It is

curative. It's not curative for

everybody, but it is curative. And yes,

it can be associated with side effects,

but you sort of have to b like I don't

want people to have a positive scan. I

don't want you to have mets. I don't

want you to have something I could see

actually cuz your outcomes are worse off

if you do. So like this whole like I'm

going to wait and keep having my PSA go

up so I can see it and then target what

I see so I don't like you're missing the

window for cure if you delay too long

and then if we see it on your skin

that's not a good thing.

So there's this like education around

salvage that needs to be had. And I

think that um the therapies are getting

better. the proton therapies, you know,

photon therapies are getting better.

There's probably a little bit more hype

around protons from a safety standpoint,

but if you actually look at all of the

objective data, objectively, there's

actually no difference in the side

effect profile, like if you look at

clinical trials of photons and protons,

they're about the same. They actually

are the same, not about the same. But

theoretically, one could argue that

there's a theoretical improved safety

with protons because there is no exit

dose with a proton molecule. Um, but

there is an exit dose with a photon. So

that's basically the main difference,

but you account for that by the way you

deliver the therapy. So these are just

sort of the nuances. I think if somebody

um is a candidate for protons, there's

no reason not to get protons. If you

know, even if it's a theoretical

benefit, like sure, like if it's going

to be 1% better for me, like sure, I'll

do it. Like why not do it if it's not at

a risk to me, you know?

>> Yeah.

>> So, good morning, Dr. McKay. Hey,

>> it's so great to have you here.

>> Good to see you, Mike.

>> Good to see you. You're helping so many

people with this talk today. Um, I have

a two-parter. So, one's a followup on

something you talked about a second ago

and then a new question. The follow-up

is probably short. You mentioned ADT

does does cause some cell death. Uh, I

always thought because I thought I had

read that it was just it creates

dormcancy. Um, but actual cell death.

>> Mhm. Yes, it does.

>> Okay, cool. Fair. Cool.

>> Yeah. And I I will tell you how we know

that. We have done studies where we give

hormonal therapy before people have a

prostatctomy and we look to see if

there's viable cancer in the prostate

specimen. And if you just do ADT alone,

just Lupron alone, about 10% of

individuals will have no cancer, no

residual cancer at all in the prostate

just from the ADT alone. and probably

about 20% if you were to add an RP, so

Abby, APA, Enza, one of these drugs, the

combination of the two in the studies

that we've done result in uh what we

call a a path response, you know,

minimal residual disease of about 20%.

So it doesn't kill every single last

cell, but it does kill cells.

>> Gotcha.

>> Yeah.

>> So the new question is on the subject of

biopsies. Um, so you know there's single

needle MRI guided or single needle

biopsies and then there's 12 core.

Where's the tipping point where a an

informed practitioner physician would

advise 12 core versus single needle or

single needle versus 12 core. So there's

actually been a study that's been done

on this at the NIH that looked at

targeted only random targeted with

random and the group in which the

detectability was the greatest was in

people who had both.

So um you know I think the MRI is only

so good um and prostate cancer can be a

diffuse process in the prostate and

sometimes when the pro when the cancer

is diffuse and there isn't a focal

lesion um you can't really like see it

on the skin. So you need to have like a

density of cancer to see a mass. That

doesn't mean that there isn't cancer

where you can't see a mass. you know,

when you're doing an MRI, it's not at

the microscopic level, it's at the

macroscopic visual inspection level.

Doesn't mean that there isn't

microscopic disease elsewhere. So, I

think in general, our practice at UCSD

is all patients with an elevated PSA

generally will get an MRI and um they

generally will get a standard core

biopsy with targeted areas. And and I

know that practice is variable. There

are some there are some practices

where they only do an MRI after a

diagnosis of prostate cancer. It's kind

of crazy

>> like we do it ahead of the diagnosis to

guide the diagnostics

but I think a target targeted short

short changes people if you only do it

targeted.

>> Okay. Thank you.

>> I'm back. Okay.

>> Um, can you give us some insight into

the thought process for the length of

how you set the length for ADT and then

also the frequency of testing and and

stuff like that? Like so, you know,

selfishly I get stuck every 3 weeks and

I wish it was every six months because

I'm not a good stick. So,

>> and I will say the frequency of testing

when we check the PSA, when we need to

do other tests, it all depends on

what what's your risk of cancer, what

state are you in, are you hormone

resistant, castration resistant,

>> um what other drugs are you on in which

those drugs require monitoring?

>> So, it's very

>> like different. it if if you had surgery

and you're five years out, like you

probably just need a PSA once a year.

Like, you know, if you're just had

high-risisk surgery and you're still

within, you know, the first couple

months, you probably need a PSA every 3

months. You know, there's different

there's different guidelines depending

on where that individual is in their

trajectory, what treatments they're on,

and what their risk is. Because the

testing should be aligned with what

somebody's risk is. If your risk is

lower, you can test less frequently. If

your risk is higher, you test more

frequently. Now, sometimes it's not just

the PSA that we care about. For example,

if somebody's on Zitiga, well, we got to

check your liver numbers and we got to

check your potassium. And it could be

that somebody's undergoing testing for

those reasons, not necessarily for their

PSA, you know.

Y

>> so that is variable. So I think in the

localized setting

um it depends. Um so if somebody has an

intermediate risk cancer and they're

undergoing radiation therapy. Um

sometimes if they're favorable

intermediate sometimes they don't need

hormone therapy. If they're unfavorable

intermediate sometimes they will do four

to 6 months of hormone therapy. If

somebody is high- risk um generally it's

a longer course and generally it's on

the order of the data are around two

years. Now I have to say there's a lot

of nuances in the way the studies were

designed. There was a study that looked

at 18 months versus 36 months to see if

36 months was better than 18. We

demonstrated that 36 wasn't better than

18. that study wasn't designed to say

that 18

was actually better, you know. Um there

was a study looking at six versus 24 and

that study clearly demonstrated that 24

was better than six. And so then there

was another study that looked at Abby um

plus hormone therapy versus just Abby

alone and that study did 24 months. So

all of these studies are a little bit

nuanced. there unfort there isn't

unfortunately a study that was done

looking at every iteration of time

interval there's a certain practicality

in the way that you approach it but I

will say there's a very intriguing

metaanalysis that was recently published

at the beginning of the year now this is

um not level one evidence not level one

evidence this is like a retrospective

meta analysis that looked at what's the

optimal duration from a lot of trials

that they pulled together. This is again

not a prospective study. There's not

level one evidence. But what they kind

of,

you know, they they had some um

uh observations that I think are

thoughtprovoking and should be taken

into account as we think about things.

Your benefit from hormone therapy

is not linear with regards to your time

from your diagnosis.

The benefit of therapy during the first

three months is not the same as the

benefit of therapy during the last three

months. And it's a nonlinear benefit.

It's likely that the beginning you're

deriving the most benefit. And over

time, if we take a two-year interval

that you're going to that your doc said

you need to be on the therapy for two

years and we look at how much bang for

your buck you're getting from every

month on that two-year scale, it's

likely that it's front-loaded, not

backloaded. So what I why I say that is

because if somebody's running into

trouble or they're like I I am done

the and they end up stopping early. Say

they stop at 18 months instead of 24

months. They've probably reaped the most

benefit in the first 18 months that

they're going to reap in the last it's

probably just single percentage points

of additional benefit from month 18 to

24. Now, this is just my biased view of

this data, but I think it's somewhat

thoughtprovoking to think that your

benefit is not the same over this 2-year

continuum and is likely frontloaded.

>> Okay.

>> Is it you, General? That one right here.

>> Hi, Dr. K. McKay. Um, thanks for being

here. Um, two two questions. One is has

to do is is there a correlation between

inflammation

in the prostate or around the prostate

and PSA counts and is you know and along

with that are there natural methods of

reducing inflammation inflammation

if there is a correlation and then the

second one when you were mentioning it

just a little while ago about

microscopic

um cancer versus the like you don't see

a growth on your MRI but you have the

you know the cancer

Um, is the normal biopsy like where they

take 14 or 16 snippets and they they

assay those or they look at those. Is

that still u an effective method as

well?

>> Yeah. So, um, good question. We're going

to break things up about the

inflammation piece first. Yes,

inflammation of the prostate can elevate

PSA. We see it all the time. People get

a urinary tract infection. they have um

you know prostatitis uh sexual

intercourse can elevate PSA. These are

all natural things that can elevate PSA.

Um in actuality there have been studies

that have been done looking at BPH and

looking at prostate cancer. And there

actually seems to be some hint of an

inverse relationship between the two.

And BPH actually tends to

there's also if you look at the prostate

where prostate cancer tends to show up

in the prostate it's it's in divergent

regions of where there's BPH. So BPH

tends to be right around the urethra

like centrally located affects people's

ability to pee. Most people who have

prostate cancer they don't have any

symptoms. Your most people their urinary

symptoms are not related to the prostate

cancer. their urinary symptoms are

related to some element of BPH or some

element of constriction around the

prostate. It's a very rare scenario to

have such a bulky huge tumor within the

prostate that that tumor is what is

causing the impingement. That's not a

common scenario.

Preferentially prostate cancer actually

tends to affect the periphery of the

gland, tends to hug the capsule. So if

you actually had like you think of the

prostate as like a walnut, right? like

around the shell of the walnut is where

the prostate cancer likes to go and the

shell is the capsule and the the nut

portion of the walnut is generally where

BPH is. And there's been studies that

have been done that people who have

really bad BPH,

they generally don't tend to have really

bad prostate cancer. And people who have

no BPH at all and no urinary symptoms

can be at risk of having a bad cancer on

the periphery. It's not pure. It's not

100% but there are these relationships

that we have observed just from looking

at data. So I think when we think about

you know your question about what are

ways to naturally decrease inflammation.

Um so if you actually have true

inflammation of the prostate like BPH or

cyitis or proctite or whatever like that

needs to be treated with like

medications or you know maybe you need

antibiotics or something like that. I

think this whole like the the kind of

handwaving of I just want to be in a low

inflammation state just in my day-to-day

health, you know,

it's hard to really pinpoint what what

to do there. I mean, it's like all the

things, you know, to to do. Get good

sleep at night, decrease your stress, um

limited alcohol use, limited tobacco

use. It's uh um you know, making sure

you're kind of in a circadian rhythm,

plantforward diet, um good protein. It's

like all of these very hard to pinpoint

things. Um, to answer your second

question, I think I uh just to kind of

summarize, we chatted about it a little

bit earlier. There have been studies

that have been done. Probably the

greatest likelihood for yield on a

biopsy is to do both a targeted biopsy

of what is seen on the MRI with a you

know template biopsy to sample different

regions of the prostate cancer to get a

a prostate to get a comprehensive view

of what's going on.

>> Okay.

>> Hi Dr. McKay. Always great to see you.

Um, we have a tandem question. Um, my

wife says about biopsies, so why don't

she start?

>> I'm just wondering if you could talk

about cribopform pattern that shows up

on a biopsy because you don't hear much

about it, how it affects treatment, um,

prognosis if you have it.

>> Yeah. So, cribform pattern is the way

that the prostate glands look underneath

the microscope. So prostate cancer we

say prostate is actually an

adnocarcinoma.

Adnocarcinoma means it's a cancer of the

glands. People can have adnocarcinomomas

of other glands in their body but the

prostate is a gland and it's an

adnocarcinoma of the prostatic cells.

Cribuform describes the way those cancer

cells are growing

like in the tumor. Okay. It's kind of

like a almost looks like a tree when you

look at it. Okay. The presence of

kbopform architecture has been

associated with a little bit more

aggressive disease. Some of the studies

are a wash that it's not significant.

Some of the studies show that it is

significant. There's also a clustering

of curbopform with pattern four pattern

and pattern 4 prostate cancer tends to

be more aggressive than pattern three

cancer. So is it is it the pattern 4 or

is it the cribopform? So some studies

have said there's really no difference.

Some have said that there is. Sometimes

it may be seen with what we call

intraductal carcinoma where the cancer

actually grows into like

into the prostate duct itself. That has

been associated with a little bit more

aggressive disease. But at the present

time that feature cribopform feature by

itself

alone is not gonna guide a treatment

decision. It's the it's the totality of

like what's the gleon, what's the PSA,

what's the stage. Yes, we'll assess

cribopform, but just sheerely having

cribopform is not the sole determinant.

Usually, it tends to cluster with other

like negative things and that drives the

decision, you know.

>> And my question is about metabolic

syndrome. Can you describe it and what

are the symptoms and what would be the

interventions for that line? So I will

say um so metabolic syndrome can happen

in the context of people being on

androgen deprivation therapy or in a low

tea state. And metabolic syndrome is a

cluster of insulin resistance that can

then lead to

elevated blood sugars because the

insulin that you have isn't working.

It's not working to drop your blood

sugars. Um it's it's actually insulin

resistance is very akin to hormone

resistance. The same kind of concept

actually where you're you're blocking a

certain thing but then the effect of you

blocking is not do it's you're not

having the desired outcome. So there can

be insulin resistance, there can be a uh

uh increase in cholesterol and uh there

could be an increase in fat deposition

and development of uh what we call

visceral fat. Visceral fat is the fat

that is the bad fat. like that's like

when you have fat in your organs and

central atyposity that's like not good

from a cardiovascular standpoint is

associated with cardiovascular events.

So I think um this is all part of the

clustering of metabolic syndrome.

Sometimes it can be with associated

hypertension.

Um most people don't feel metabolic

syndrome. The thing that they feel is

I'm gaining weight. My pants are getting

tight maybe you know but it's not

something that you feel. You don't most

people don't feel when their blood

pressure is up. Most people don't feel

when their blood sugar is up. Um you

know there's some that are highly

attuned to their body and can make those

kind of determinations just from a lot

of checking and knowing. But most people

don't feel anything. But it's really

important when you're on hormonal

therapy that those things are being

checked for. And I think sometimes what

I've seen is is there isn't like an

owner of checking for those things.

there's kind of like a well is the

primary care going to do it? Is your

medical oncologist going to do it? Is

urologist going to do it? Is your rat

aunt going to do it? So like in my

practice I try to like not assume that

somebody else is going to be checking

the blood work associated with the drugs

that I'm giving. And so we periodically

will check at least on a once a year

basis for somebody that's on hormonal

therapy to check their lipids and check

their hemoglobin A1C and get a DEXA scan

and do those things. In different

practices, it may be different. Like in

a urology practice, they may say, "Hey,

make sure your PCP is doing this." And

there's nothing necessarily wrong with

that. It's just, you know, making sure

that somebody is dotting those eyes and

checking those tees, you know.

>> It does,

but it's not easy, right? It's not an

easy reversal process. And so you stop

the hormone therapy, then you need to

wait for your testosterone to improve.

And then body recomposition takes a lot.

It takes months, years sometimes. And so

the best

thing to do is like prevent it from

happening in the first place, which is

also really really hard to do because

you're like, I just got a cancer

diagnosis. I'm on this therapy. It's

changing the way I like I'm tired. like

and now you're telling me I got to work

out harder than I ever did in my whole

entire life. Like it's crazy. So I think

we need to make sure that the resources

are are in place support individuals

like things like lift strong nutrition

PT referrals all these things um are

really important and it and also

assessing mental health because

sometimes people get really down and the

reason they don't want to they're just

like sad and they just don't have the

the get up and go like they used to

because now they're on ADT and their

ambition is down and so I think it's

making sure that you're comprehenive

ensively assessing all of those things.

>> Oh, got one here. There you go.

>> First of all, thank you for giving us a

good portion of your Saturday.

>> I

I had surgery 33 years ago and I've been

battling this ever since because it

returned.

I uh

have had essentially the same doctor the

whole time, a urologist, and I liked him

because he was uh I stud I've studied it

pretty hard the disease and uh I kind of

keep up with everything and he but he's

gone along with a lot of things that you

probably wouldn't go along with with

other doctors or with other uh uh

patients And

I know I probably should have had an

oncologist

before this and but he he kind of thinks

it's okay where we're going. I'm on

extending now dutasteride and uh and

estrogen which I've been on for four

years. That's a for instance what he

went along with when a lot of doctors

wouldn't.

And my question, couple questions is

about you. How how do you practice? I

mean, are you

real strict in what you prescribe for us

or or do you take the patients uh input?

Uh I know you take it seriously, but do

you how much of it do you take or do you

just put your foot down and say this is

the way we're going to do it?

Well, that's generally not my style of

putting my foot. I just get trampled all

over. I've got four kids and generally

I'm swayed in multiple different

directions constantly, but I don't think

that's what patient care is about.

Ultimately, at the end of the day, it's

serving the needs of our patients,

right? And everybody comes to the table

with different needs and everybody comes

to the table with different values. And

I think I've actually learned and

matured over my practice around that

point because

my job is to make sure that you're

informed. Make sure that

you are aware of the risks and the

benefits of any specific choice or path.

Whether you decide to go down my

recommendation or not is your choice.

Like it is your you are you're you all

are grown men. It is your choice. It is

not my choice. My choice is to provide

you with the options and give you a uh

objective assessment of your different

choices.

And if there's something that's going to

be detrimental, I will let you know. But

if you select to go down that

detrimental path, that is the path that

you select to go down is, you know, if

it entails a prescription of something

that I actually think may be harmful, I

will not prescribe that medication. Um,

but I won't necessarily preclude

somebody from going to somebody else to

prescribe it. I will just not prescribe

it. But generally, it's a balanced uh

conversation. And for each person, it's

different. I I tell people, you've seen

one prostate cancer means you've seen

one prostate cancer because every person

is different. And you can't like, you

know, for people that are on the

internet and blogging and this person

then that, this person then that, that's

just like garbage out there. Like quite

honestly, it's total garbage because

it's it's hard as a lay individual to

understand the complete complexity of

somebody's total case and everything

going on with them. Everything going on

with them. Not just medically, not just

what they choose to share on the

internet, but everything that's going on

with them. otherwise it may have

impacted a a provider going down one way

or another. So I think it's a very a

personalized

you know and I think the most important

thing is that you have a therapeutic

alliance with your oncologist or with

your whoever your doctor is in any

setting not just cancer with your

primary care with whatever there needs

to be a therapeutic alliance there. It's

really important. It's a relationship,

you know. So,

>> well, that's that's just what I wanted

to hear because I'm seriously

contemplating

trying to get into your practice if it's

not too full.

>> Yeah.

>> Uh, thank you very much. You're welcome.

>> And I want to step in for a moment. Um,

sir, did you say that you're still with

the same urologist who was your surgeon?

>> He's talking to you. No, I

my I got with him about u of those 33

years I've been with him probably

20 30 probably 30

>> cuz I'm in the unique position I'm in

the unique position that I actually had

surgery from the same surgeon as you and

then I became a a patient of Dr. McCay's

and so I certainly saw much more cutting

edge ideas and diagnostics and uh and

and definitely much better bedside

manner too. So uh I highly recommend

making a change.

>> We're here to help any way that we can.

>> Yeah, he said the same.

>> Say Erin, you said uh the surgeon did

your prostctomy. did his. I'm I'm pretty

sure I'll I'll come back in a minute.

>> Yeah. Wild cast that over the

>> Okay.

>> Okay.

>> Um how much progress is occurring with

genetic and genomic profiling of

patients and their cancer to

personalized therapies for greater

compatibility and effectiveness?

>> Yeah, I think there is tremendous

progress um that is being made. Um

the thing about it is

we tumors are incredibly

diverse and heterogeneous

and this is the Achilles heel of

precision medicine.

Because of that diversity

>> and the limitations of our testing,

we would be silly to think that every

single prostate cancer cell in any

individual's body is exactly the same

cell that has the exact same mutations

and the exact same susceptibilities.

And when we test cells, we don't test

every single cell in your body and

assess the complexity of the

heterogeneity

that exists.

And while precision medicine strategies

have certainly helped us, there are

certain limitations

that not to say are insurmountable that

are just inherent to the sheer nature of

how complex cancer is.

So there has been tremendous advancement

and the other thing that also has become

increasingly difficult is it's

one is do you have a drug available to

drug one is is are the mutations

actually pathologic

meaning okay you get back a genetic

report and it's got five mutations on

it. Which one of the are are some of

those mutations truly driving

pathogenesis and need to be targeted or

are some of those mutations just bypass

our mutations that aren't driving

pathogenesis? Okay, so now I have these

five mutations. Maybe half of them we

think are pathogenic.

Um, so do I have drugs to target each of

those five mutations or each of those

four mutations? Okay, I have drugs, but

can I compatibly combine those five

drugs together to target all of those

mutations?

Okay, I have all of that, but this

tissue sample that I did, this tissue

sample was from your prostate. It was

like leftover tissue sample from your

prostate.

Is that actually what's happening with

the rise in PSA now? So, it is

inherently very complex. And I think

sometimes when we see things like on the

internet or whatever, it's like a very

simplistic like median drug this why not

like why why haven't they figured it out

already? It is so incredibly complex and

I think that's going to be the Achilles

not say the Achilles heel. I'm excited

about precision medicine. I think we're

going to get places with continued

strategies to do this better. But I'm

also excited about strategies that don't

necessarily target the therapeutic

vulnerability, but for example,

allow the immune system to do what it's

supposed to do. How can I like your

immune system is the best, you know,

army that you have against your tumor?

How can I leverage your immune system?

or you know if an alpha particle is

going to kill whatever it is DNA that's

in its path

how can I leverage getting that alpha

particle to the bulk of your cells and

then having some bystandard effect from

the alpha particle going to the cell

next to it above it below it that

doesn't have that specific target so

it's I think I'm I am excited about

precision medicine but I'm actually

equally if not more excited about these

other mechanisms as well.

>> Yeah.

>> Can I uh can I jump in on that?

>> You just made

it back.

So, I I think that uh what you're

describing is something that's kind of

been on my mind quite a bit, which is

when you think about natural killer

cells and the fact that there's certain

u therapies that can in increase those

uh cells within your body, is that

something that you think uh is is

beneficial? In other words, if I were to

um you know find something on the

internet that says this will increase my

natural killer cells, is that something

that you would advocate or would you

just say uh no there's there's other

ways to do it?

>> Well, I'd have a lot of questions about

it. If you found something on the

internet saying do this to increase your

natural killer cells and buy this

product from me for, you know, non

obviously,

>> you know, non FDA regulated product that

you're going to pay cash for, not

covered from your insurance. there's a

marketing angle there.

>> No, I I get that. I'm I just use that as

an example, but I mean because there are

there are, you know, realistic ways of

of accomplishing that.

>> Yeah. So, I I've just I'm I put that the

reason I say that and in this kind of

like fictitious kind of way is is

honestly um there is an entire industry

that prays on cancer patients and I see

it in my clinic every single day and

it's sad.

cancer patients, older adults, you would

do anything if somebody told you it was

going to control your cancer.

There's an unregulated industry that

prays upon that. And you need to look at

that with the same level of integrity

and rigor that you approach me or or

your doctor when we go to prescribe you

a medication.

So there's this whole industry. It's not

like the neutrautical industry is an

unregulated ind. I can make

a B12 supplement in my garage, put it in

a bottle, and sell it. And it's okay.

It's actually okay to do that. Totally

fine. It's not regulated. So, please be

careful about what is up there. I've

I've had patients who have put their

homes on lease for intrarostatic

injection therapy that they thought was

going to cure their cancer. like lost

their homes doing this.

I like I don't even know who like

there's like like of course it didn't

work. There's like no data, but like

nobody knows any better, you know? So

like please be careful about those

things. Um because it's um you don't

want to be caught in that. And um I

think oncology patients and older adults

are the most vulnerable

um for these sorts of things. Now to

speak about NK therapy um I do think

that it has legs but we haven't figured

out an effective way like there's

actually been like just like there's

CARTT cell therapies there's CAR and K

therapies that are being developed and

emerging but they're still at their very

very infancy. um because of safety and

toxicity and how do you actually enhance

these cells, administer these cells in a

manner that's going to attack the tumor

and yes enk cells are important but

there's also your te- cells your

cytotoxic tea cells that are equally as

important um there and I think inducing

like a cytoine storm in the context of

turning on your NK cells is also

something to be contended with But I do

believe that there's like in 10 years

from now, my hope is that we're going to

have a lot more of these targeted

immunologics that are going to really

change the game. Um especially in

prostate cancer. Yeah.

>> One quick followup. Um I know you were

involved with the uh the I predict uh

trial. Um you have any uh nuggets from

that trial that you feel are are really

something you're excited about? Yeah, I

love that trial and the it's kind of

like a uh unicorn study and you sort of

have to like be a believer, right, with

that trial. But again, it speaks to the

same kind of concept or the same issues

that I was telling Ron about like you

know what you biopsy, the availability

of the drugs, how do you combine drugs?

But that trial tried to leverage that in

a very practical kind of way. Um the

drugs that we utilized were drugs that

were all FDA approved

and they were drugs that are on the

market but may have been used for other

things. We to actually get this to work,

we had a specific person that was our

drug acquisition

like uh uh like administrator. Like

literally her job was like when the

molecular tumor board came up with a

recommendation and it was a drug that

wasn't FDA approved for X disease to go

down and try to get that drug for the

patient like because it's like sometimes

going through prior authorizations and

going through drug company insurance

approval like there there are a lot of

barriers to actually being able to

access. So that was actually probably

one of the hardest things. But then

also, you know, the not to say the

science around combining the drugs, like

we we basically dose reduced everything

when we were combining like anytime we

were combining two or three drugs that

had never been combined in history

together. That's what we were doing in

the context of that trial. We would 50%

dose reduce and aggressively

aggressively monitor. But I think what

the trial demonstrated was that a

matching strategy

did actually improve outcomes for

patients. Patients did better when they

were matched than when they were not

matched. Um, and how can we amplify

that? It wasn't like a trial of cures

per se, but

we kept the disease at bay for many

patients for an extended period of time

beyond what standard of care would have

done.

Yeah.

>> And what was the name of that?

>> It's called predict. It was called

predict and I predict. There was two

studies. One it was late line, one that

was front line. Yeah.

>> Who did you?

>> No. Go ahead. Next gentleman next.

>> I'm glad to have the opportunity for

another two questions. They'll be quick

though. Two months ago we had other

members of the A team in here. We had

doc doctors Rose Rossy Muntz Sebert.

there might have been someone else.

There wasn't complete agreement if you

decide that radiation is the course

you're going to utilize on the use of

space or hydrogel.

The second question is what's your

opinion on the higher dose shorter

length of time treatments the cyber

knife nano knife. Thank you. Yeah,

that's all emerging. Um, I think as

we've figured out how to better

administer radiation therapy, the thing

about the spacer or the hydrogel,

there's never actually been a formal

study where you flipped a coin, half the

patients got it, half the patients did

it, and you looked for outcomes to

assess who did better. There really

hasn't been any formal study. And that

study quite honestly would be a little

bit difficult to do. It's not to say

that it couldn't be done, but at the end

of the day, if I wanted to prove to you

that putting in a spacor is the right

thing to do like it would it would take

a study like that. It would take a study

where we randomize half the patients to

get it. We randomize the other half to

get it. We had a substantial number of

patients where we could assess the

rectal toxicity and decide, yeah, is it

going to help or no, it's not going to

help. So, in some scenarios, it could

hurt because you're injecting a gel

and pushing the rectum away, but what if

you're pushing tumor away? What if

you're pushing tumor cells away?

So, and there's also it's not

necessarily a fun procedure to have

done, quite honestly. But I don't think

that it's a mustdo. I think it's a can

do. And in some scenarios it's a don't

do depending on how extensive the

disease is. Okay. Now to answer the

question about SPRT. So SPRT there's

been like a renaissance in radiation

oncology with the introduction of SPRT

where you could deliver highly focused

radiation therapy at high doses um with

limited toxicity to surrounding tissue

and kind of more focused effect.

So in the context of people who have

high-risisk disease where there's a

focal area that's identified on an MRI,

there's been actually studies that

suggest that actually boosting that area

in addition to treating the rest of the

region actually improves outcomes. They

may have talked about a study called the

flame trial where they boosted that in

addition to treating everything else,

they boosted the area that they saw on

the MRI. Um the thing about

hypofractionation

is

you know

your the disease really needs to be

confined for you to do SBRT to the whole

gland right like if there's any evidence

of like extra prostatic disease

you don't want to do SBRT because there

could be microscopic cells out of that

field so I think in the context of

people having intermediate risk disease,

everything's confined to the gland. You

could conceivably do SPRT

um where it would be done in 5 days or,

you know, maximum 10 days, not having to

do a long course and everything's

confined. So, I think the data is

evolving. I don't necessarily think it's

from an oncologic standpoint, I don't

know that we've proven that SPRT versus

IMRT is better. We've proven in the

later setting where we combine it when

there's a focal lesion, it is better,

but sometimes the uh SBRT it's more of a

convenience thing. And I have to say a

lot of that emerged from COVID because

we could not have patients coming into

the clinic for two months at a time

getting radiation therapy. So, we had to

think of how can we decrease the course

of treatment but not worsen outcomes.

So, I guess what I'm trying to say is

that the the long-term outcomes of those

strategies are still early, right? Cuz

they were just like if we're looking at

5year and 10 year and 15 rates of

survival and not having mets. Well,

these studies just were done, you know,

not too long ago. So, I would say that

there is some uh not to say um it's not

so black and white. There's a lot of

gray in the area and some of it's

probably preference as opposed to truly

validated in evidence. Yeah.

>> Did you have a question?

>> Yes, I do.

>> Um

>> hi. I had my radiation finished last

April and I had my last Lupron shot in

May and I'm still experiencing hot

flashes throughout the day and at night.

What's the halflife of Lupron and when

can I anticipate the hot flashes to go

away? I'm take currently taking black

>> kohash

>> and that seems to be doing nothing.

>> So, first I'll say is it's not a Lupron

half-life problem.

It's a turn on the access problem. So

it's not like the drug is still in your

system. The drug is not in your system.

You've taken away, you know, the drug,

but this Lupron is an agonist. It

continuously stimulates the receptor

until the receptor shuts down. The

receptor has shut down. Even though

we've taken away the drug now, the

receptor still hasn't woken up. Your

problem isn't you still have Lupron in

your body. your problem is the receptor

hasn't woken up. In some scenarios

it can in some scenarios it may never

wake up and um in those settings there

can be things that can be discussed

around actually trying to give people

back testosterone but that's done in a

very um you know uh personalized manner

depending on what your risk factors were

and what your tea levels are and how

much time you are out from end of

treatment to not put you in harm's way

from a prostate cancer standpoint.

Right. So, um the Lupron itself, you

know, it's uh I guess the halflife is is

dependent on like the depo injection,

right? Like it's a slow release

medication. And so if you had a

three-month injection, you know, from

your last shot around the three month

and then if you were going to add maybe

four weeks or so on the back end of

that, the drug itself is probably out of

your system, but its effects are not.

Now, how do you treat hot flashes is

another question, right? Like there's a

lot of medications that are out there to

treat hot flashes. Um, and I I should

maybe step back and not just say

medications. There's a lot of strategies

to employ to treat hot flashes. Those

strategies could be um modifications in

the AC settings in your house, the

clothing, using a cooling pad, fan at

night, all of these different things.

There's one of my patients told me about

this new watch that you like wear it and

it's not really a watch, but it's like

kind of what is it? An ember wave or

something and you get a hot flash and

you push the button and it's right by

your radial artery. So it sends a signal

to the brain saying I'm cold and it's

supposed to turn off the hot flash.

Whether it actually works, I have no

idea, but some patient it's 200 bucks on

Amazon, so I don't know if it's worth

the money. Okay, but so there's that.

There's there's medications too, but the

medications themselves are not like

great. Like there's like um you know,

venaxine

um may uh it's a lowd dose estrogen can

also be used. There's oxybutin, there's

gabapentin,

some of the medications, it's kind of

like, you know, but but it causes this

other side effect or this other thing.

So, if it really is debilitating where

somebody's really not able to get

restful sleep at night or they're just

um you know, the frequency, the

intensity is just too strong, I that

these medications can be uh considered,

but there's no like magic reversal. I

wish there was.

Yeah.

>> Thank you, doctor, for being here. We we

really appreciate your time.

>> U my situation, my dad had prostate

cancer and his three brothers. So, I've

been active surveillance all my life. I

knew I would this going to be dealing

with this. I had surgery radical

prostctomy in 2024. I decided to do that

route after I PSA 8 uh Gleon some sevens

and actually here Dr. uh Rose told me

about the decipher test. I'm with Sharp.

I didn't even know about that. Initially

I was denied the decipher. I appealed

it. I I got the results. It was 7 and so

I had the surgery. Uh it went great with

PSA 01. It's been climbing up a bit.

They did send me for a PSMA PE. I guess

that's the gold standard. Um, I had a

fall before my surgery, like 10 weeks

before. And they they did see on the pit

a spot on my rib like you talked about

earlier. So, we're hoping that spot is

from my seven foot fall from a ladder.

They said it could be a heel fracture. I

never thought that would be a blessing

in disguise because I get I get approved

for PSMA because of that. U my question

is the PSA is climbing up like 0.1 now

from 0.1 from you know 0.01. Um at what

point I've been told by a doctor don't

worry about it till it's in the single

digits. Another doctor says oh maybe

around 02 we start thinking about

things. What do you like to do to follow

up, you know, to keep an eye on things

>> other than PSMA? Is that the best? And

also a PET scan.

>> Yeah. So, just to kind of step back, I

think I'm going to put this in the

context of monitoring PSA post-RAD

prostatctomy as opposed to medical

advice for your specific situation.

Okay. So, post radical prostatctomy,

the threshold to define relapse is a PSA

of 0.2 two or higher. That threshold was

defined during an era of non ultra

sensitive PSA testing and there hasn't

been a recalibration of that 2 with

newer tests.

That being said, I think for most

individuals if their PSA is less than

0.1 I would do nothing. Um I would keep

monitoring if it gets within the 0.1 to

2 range.

Some individuals may want to pull the

gun early with regards to doing

something about it. Most people don't.

Um, with regards to the timing of the

PSMA PET, the um, the lower the PSA is

at the time that you go in to get the

scan, especially when your index of

suspicion for metastases or something

showing up in the pelvis is lower, the

likelihood that you're going to see

something is actually low. um and

probably less than 10 to 15% for people

being at the 0.2 range. It's not to say

that it can't happen, but the likelihood

is a lot lower. Um, so the flip to that

is in somebody who's postradical

prostatctomy and has not done radiation

and they are willing to do radiation.

They're not of the mindset of I'm never

going to do radiation because there's

some people that are in that category,

that means that we are threading a

needle with regards to when we can get

the radiation in with a with an intent

to cure. And so generally in that

context I would want the radiation to be

delivered when the PSA was less than

0.5.

People have better outcomes with

radiation when the rad when the PSA is

lower. Now there are some people that

just can't make up their mind about

radiation and they're afraid of the

radiation or don't want to do the

radiation or they maybe had a structure

and they're just like afraid of the

radiation and they just don't want to do

it. And that's okay. In that context, I

would drag my feet because the next

thing that technically is a standard of

care is some form of hormone therapy.

And unless the PSA is high enough and

unless it's doubling at a rapid rate,

then I wouldn't do any hormone therapy.

So, I think it's nuanced depending on

the PSA, the absolute number of the PSA,

the doubling time, the PET, your

baseline symptoms and risk. And

everybody who has a family history or

has a unfavorable intermediate or

high-risisk cancer should undergo

genetic hereditary testing. Um it's in

the guidelines. Um everybody should be

offered it. I'm of the mindset that

every person with prostate cancer should

get germline testing, but that hasn't

entered into the guidelines. But

unfavorable intermediate, high-risisk,

you should absolutely get hereditary

testing.

>> All right. Thank you. They were going to

biopsy the spot on my rib, but they said

it was too dangerous because it was so

close to my lung.

>> Yeah.

>> So, we're just keeping an eye on that.

>> Yeah. I think um this is the PSMA PET

positive isolated rib lesions in the

context of an intermediate risk cancer

is like 25% of our tumor board every

single week because it comes up so

frequently and it's just you know the

likelihood of a false positive is so so

high. um and you're not going to make a

treatment decision and and put somebody

in the bucket of metastatic stage 4

cancer based off of that. You know that

there's a lot of implications that come

with that label, you know.

>> Um I'm going to chime in here. Yeah, I

had my prostctomy and and Lupron and

radiation in 2014 and I was less than

0.001 001 and three years ago it started

climbing

and I was really wrestling back and

forth because I talked to people that

waited too long and it was all in their

bones and they had to go straight to

chemo and I had seven PSMAs

in August. My PSA was 14.3. I was 13

when I was a Gleason 9 and they finally

saw on the seventh one a couple shadows

on some ribs. So, I started Lupron, but

I was going back and forth. Uh, you

know, I wanted to kick it down the road,

so I didn't spin the bullets. The other

is I've heard people waiting too long

and bam, it's in in their bone mar and

then next thing you know, they're on

more radical treatment. So,

>> just your thoughts on that, please.

>> Yeah. So, I think, you know, yes, we

have a PSMA PET scan that can be

utilized for detection. It's not

perfect.

And I think there's a group of

individuals who have high-risisk who

have a high-risisk biochemically

recurring cancer with a negative PET

that warrant treatment. I don't want to

wait for you to develop metastases.

If your PSA is greater than one and your

doubling time is less than 6 months and

your PSMA PET scan is negative and the

PSA is ratcheting up that I check it and

it goes from 1 to 2 to 4 to 8 in a 6 to

9 month period, you need to start

hormones even if your PSA is negative.

And there are studies that have now been

done. And I know this study is probably

um you all may have heard of the embark

trial that did just that. Uh I should

step back and say the difference with

embark is they didn't have PSMA pets. It

was done a decade ago at a time when we

didn't really have PSMA pets that were

systematically getting done and patients

were actually blinded to PSAs in the

context of the embark trial. But this

trial basically demonstrated that in

people who have a biochemically

recurrent tumor, meaning it's their PSA

is rising after definitive therapy,

whether that be surgery or radiation,

the rate of rise is fast. And the rate

of rise wasn't made by just one or two

PSA readings. You determine a doubling

time by three to four sequential

readings spaced apart where you can

actually get a sense of the doubling

time. Because sometimes patients come in

and they're like, "It was 0.02, 002 and

now it's 0.04 and it's 008 it's

doubling. I'm like it's not even 0.1.

It's not doubling. We don't we don't

have any points on the curve here. We

got to wait. Okay. So you got to have a

substantial kind of number. But in that

context PSA greater than one and um

doubling time that was actually less

than 12 months. they uh were enrolled to

receive hormonal therapy and intensified

hormonal therapy and the receipt of

hormonal therapy in that context

resulted in a delay significant delay in

the time of metastases and also improved

overall survival. It's a overall

survival benefit. Yes, it's being on

hormones, but you're also improving

survival. So, I wouldn't always just

wait for something to show up on the

PSMA PET scan.

Um, and just so I had a 14.3 I I'm

sharing this because it's a positive. It

went to December 0.11 and March 06.

So we like they said it's two words, not

a sentence. There's a lot of treatment

out there and you got brilliant people

like that. So there's stuff out there

working for us rather.

>> Yeah.

>> Question over here.

>> Excuse me. Uh thank you for uh always

coming over here give us that giving us