BCG Maintenance Full SWOG Course

[Music]

so I've been given the task of you know

we've got the debate here and it's

always these are always the fun ones but

this unfortunately I've been given the

easy part which is supporting what we

all most of us are practicing which is

the full SWOG course and so we'll make

this pretty quick and you've heard a lot

of it already from dr. cooks and so

we'll kind of unfortunately have no

financial disclosures so I'll briefly

review the swab course I'm not going to

do too much because this has already

been reviewed by Mike and and you know

then the next question is you know

guidelines what's recommended white

papers and it's really easy to sit in a

committee and say what everybody should

be doing because you might have your

practice your environment in an academic

institution or ivory tower and then

other people have other things in other

considerations and patients are

different and they're not all the same

and there's a lot of things that a lot

of these studies haven't controlled for

and will you know briefly talk on that

so I think knowing what really happens

is another issue right what really is

going on for all of these patients and

their ability to get back to the office

and things like that but ultimately you

know I'm gonna share with you that I do

I am a believer in BCG because I think

it's really one thing or the other

either BCG works or it doesn't work it's

one or the other I don't I don't I'm not

as much I don't buy into that there's

kind of a in-between road either

patients have an immune system that's

going to respond appropriately or they

don't some of you have maybe been at

this course before I've seen some of the

basic work we've done showing that you

know we and and really this is now

supported by all the PDL one and pd1

work that's being done demonstrating

that either your immune system is ready

to be primed or it isn't so the classic

you know swag study that was you know

published in I think it was in 2000 that

was headed up by you know large group of

well-known bladder cancer experts in

particular Don lamb I don't know if he's

here today he often comes to this

meeting was the cannot strain and the

bottom line was you you got induction

BCG and then you had it at three and and

the induction was once a week for six

weeks and then he had once a week for

three weeks at 3 6 12 18 24 30 and 36

months and it's once a week for three

weeks and you know there are variations

on that because ultimately what you're

getting is essentially three months

three years

every three months for the first roughly

first year and then every six months for

the remaining you know two years of kind

of stimulating that immune system again

kind of revaccinated if you will and and

I think it's a lot more complicated than

just stimulating a th1 response or that

you know cell mediated response in the

body because we know that patients that

whether they're PPD positive or not it

may or may not make a difference on how

they respond no different than whether

someone's PDL one positive or not if a

tumor is whether it'll respond to our

immunotherapy that's out there so it's

definitely much more complex than this

but this is what we've got and this is

how it works so why do we recommend it

and really comes down to this and that

is that in just about every randomized

or retrospective study that is out there

maintenance gives you a significantly

decreased risk of recurrence and the

original study demonstrated almost you

know half the recurrence rates when you

as far as recurrence free survival you

know seventy six months with when you're

on maintenance but it was only thirty

five months or 36 months when you had no

maintenance so it's really hard to argue

with that now how could you argue with

it they use the cannot strain that's

really not available here in the US I

think everybody uses theis right now

there's a trial the Tokyo trial which is

the SWA guess s1 6:02 looking at trying

to come up with some other strains for

us to potentially use which is the Tokyo

I think it's one seven two strain one

arm compared to BCG standard tights BCG

versus the Tokyo strain with an actual

vaccination 21 days prior to getting it

so that we can have other options we've

all lived in that world of you know BCG

not being available to us or to our

patients and having to you know

essentially strategize who's going to

receive it and that's when we all cut

back on maintenance you might remember

I'm sure all of us haven't encountered

that years ago so the one thing that

wasn't determined by this trial was did

it really change significantly the risk

of going onto cystectomy or getting

radiation or some sort of systemic

therapy and and that wasn't really

measurable I don't know that the trials

necessarily defined and designed well

for that and are people who argue

against maintenance or using maintenance

to this degree would say that the

overall

survival was the same and in the two

groups roughly a difference of 5 to 8%

nothing all that significant what else

and what do I use I'll tell you here in

a second but what else are the other

issues with this trial well there's a

lot of factors even dr. Cook has shown

you how well you resect the patient

originally is going to impact how well

the patient is going to do from BCG you

can't just leave them full of tumor and

give them BCG it's not going to work I

mean you effectively have to have a

little bit of a raw surface after the

resection so you want to do it at about

three weeks no no no later than a month

of to six weeks because otherwise you

might have new tumors and you need to

resect gross tumor doesn't respond to

BCG okay and the other issue is so these

trials in control for the TU RBT and the

and the quality or the effectiveness of

it and also they didn't control

necessarily for how the vaccine was

given how many interruptions there were

you know patients come in they have a UA

that's positive and they get pushed off

though they might have hematuria all of

these things that are very challenging

to control for in any trial but what do

I attend to use I actually use a little

extra BCG because as I said before I am

a believer that either you're a

responder or you're not a responder and

what that comes from is most of us think

that BCG stimulates that cell mediated

immune response now why a person gets a

tumor in the first place if your body's

doing the right thing is it should be

manifesting a cell immunity ated immune

response and why these tumors are there

is either one of two things in my

opinion and again this is opinion we

have one study that's been published and

I've demonstrated here at at this

meeting in the past is that either your

immune system didn't do the right thing

and you have a tumor or immune system

did the right thing and the tumor has

evaded the immune system and that's

where I think the whole PDL one pd-1

thing is come on come into play and why

we're gonna see these trials like a

tease ilysm ad that doctor Cookson

talked about and and although those

drugs seem to be the panacea for

everything at this point but we'll see

just like when TK eyes came out for

renal cell you know we all have to

temper a little bit of our excitement

but nevertheless because I think people

are responders and we've all seen these

patients that come in with CIS or

high-grade t1 you resect them you put

them on BCG and five years later you

still haven't had a recurrence of any

high-risk disease you might

have you know a little TA here and there

but those are the ones that I think

benefit the most I also believe and a

lot of people have demonstrated that if

they actually have significant symptoms

those irritative symptoms they keep

calling your office about they've

manifested a traumatic immune response

and they often do the best as well so I

ramped it up if it's working and so I

tend to do actually every three months

until they get so it's one extra

treatment so it's three six nine and

twelve and then they get 18 months of q6

I use it in every CIS patient and t1 as

far as ta there are some people who will

use it even in low-grade ta when you

have recurrences because you know you've

resected them then they come back again

and your sec them you come and you think

you should use the BCG while it's

appropriate you can consider using it I

really don't use it as often I think

high grade ta is something that is high

risk disease and you should use BCG very

judiciously in those patients because

often times I think they're not resected

enough and it's that enhance cystoscopy

it's gonna make a difference so what

happens in the real world we've kind of

referred to this already

some patients miss a dose sometimes more

than one and some miss several they

can't get through their maintenance so

that's one of the downsides to BCG is

that tolerance is an issue some of these

patients will have such significant

urinary symptoms and there UAE's come

back or their gram stain's come back and

everybody has a different way of

determining who's going to get their BCG

that day but all of those play in a play

a role and influencing how we treat our

patients finally some patients have

their own ideas of what they want to do

you know they don't necessarily want BCG

they don't want to come to the office as

frequently it's not that easy for some

patients if you're drawing from multiple

communities and so I think you have to

really strategize also for those

patients as well so what's the

conventional wisdom I think the

conventional wisdom is that BCG is for

CIS and high-grade t1 it's interesting

because I can very rarely imagine or

count on one hand off and I see

low-grade t1 that was in the guideline

just as a comment I mean you almost

start to suspect whether the pathology

was read appropriately I think you need

to get induction on board within about

three to four weeks from the resection

there used to be this fear of you know

BCG OSIS and I think that if you get a

good response and you're first

surveillance system which we do in the

operating room actually and re biopsy

and go and resect and to me that's the

most definitive way to know if someone

responded to their therapy well what are

the harms well you know I think the BCG

osis I cannot honestly remember the last

time I had such significant BCG oh so

the patient had to be admitted to the

hospital

you know dosed up with steroids and the

appropriate anti TB drugs

all of those things they're so

infrequent even though they're you know

it's out there and such a concern it is

inconvenient to do BCG frequently and

for some patients and I think you have

to then tailor your treatment based on

what their availability is to come in

and I think you need to decide with your

patients what your goals are you know

you have some patients who are trying to

spare their bladder and salvage their

bladder as long as possible what are the

comorbidities you need to take into

account all of those factors are they on

steroids for polymyalgia rheumatica and

then you may not want to use BCG and try

some alternative therapy all of these

things play a role but ultimately at the

end of the day the data speaks for

itself

it's in the guidelines it's been

referenced numerous times and I would

just say just do it do your maintenance

BCG and decide for yourself and your

patients whether you find the ones that

can't tolerate or if a recurrence and

then you can go you know the other way

following the guidelines so finally

after 18 months with no recurrence does

it really matter that's the real

question should you go to three years I

think yes and I usually tell my patients

it's working why ruin a good thing you

know we can sit here and say question

whether we shouldn't but if they're

tolerating it well all they're gonna get

is about three or four more treatments

you - we'll finish it up does it really

decrease recurrences yes does it matter

if they have symptoms I say yes and then

you should give them even more because I

think they're having a great response

you just got to find a way to make that

happen

you