Intermittent ADT - looking to understand latest views on criteria for doing it

1. I'm starting to research intermittent ADT (IADT). I am on continous ADT. More
info about my situation below in 3.

a. I have just a brief time to learn more about this and then see if its
something I can do, since my next lupron shot is 7/5 and would need to cancel
that appointment one day in advance.


b. I don't see a pca expert oncologist and am not able to leave my area to do so.
My oncologist is a community one, and said it might be ok to do iadt and encouraged me first to get a feel about the pros and cons as applicable to my situation, since they know I need to research things.


c. I have read and browsed many, many articles and studies about IADT, and IADT vs CADT,
even though hard to understand many of them, and some are older and might not reflect the latest
thinking. Thus wanted to ask here about what you think the latest views are in general on some
things related to IADT, and also, if you have been or still are doing that,
what your experiences are/were.

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2. Assumptions for my questions

a. I am assuming here that one is still hormone sensitive.

b. For the sake of these questions, am assuming one is like myself, getting just Lupron
or related, and not ADT 2 or ADT 3.

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3. My history and situation:

a. gleason 7(4+3) multiple cores - 2010
b. imrt with 6 mos of ADT - 2011, no surgery or other treatments done
c. psa starts rising past 0.2 - 2015
d. psa gets to 4.5 and axumin scan done - July, 2017
e. axumin scan shows spread to various pelvic lymph nodes and a bit further up
(para-aortic). It does not see any bone issue.

f. ADT started - August, 2017 - is only lupron and not ADT 2 or 3
g. psa was 0.3 for a few months, then as of 2/2018, 0.2, 4/2018 was 0.2
Testosterone has been <3 (don't know if thats the labs lower limit or not)

(next psa and T labs will happen soon and of course I realize those results
might have an impact on this sitution)

h. age 71
i. ADT side effects as per labs show some anemia, some elevation of LDL, and
can only assume the other effects related to bones and muscle and other things
are happening.


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4. My questions:

a. understanding criteria if and when to start iadt and what criteria - ie how low T and
psa nadir should be, how long one should be on continous adt first, how long should the
psa have been at that nadir value while on CADT, etc ?

(have read that doctors might disagree on which psa and T numbers and
timeframes here)


b. understanding when to re-start ADT - what are the criteria - ie imaging
negative, T and psa at a certain value, etc ?

c. understanding if someone with metastatic spread to pelvic lymph nodes only
can do IADT ? (this is my situation)

that is, if previous imaging before ADT when psa was high did not show spread to bones but to
the pelvic lymph nodes - does current thinking view tht IADT could happen or not ?
(have read this is controversial)


d. understanding your experiences doing IADT and did being on it help
reduce some side effects and if so, which ones - am especially
interested in blood count values and bone effects, and lipids and
other labs that might reflect ADT impacts:

- how long were your on and off cycles (until you had to
stop due to resistance or that drs felt CADT was better for some
other reasons ?

- what were the nadir values of psa and T you had while on ADT for each cycle ?

- what were the psa and T values you used that led to restart ADT ?

- did doing iadt extend your time until resistance ? (if that applies
to you)

- do/did you have imaging done when on iadt as psa gets to some higher number,
at which the imaging will be able to perform better ?
(so to help see if IADT is still an option in cases where your dr would not
recommend IADT if it was metastatic ?)


- did you take adt 2 or 3 medications while doing iadt,
even if you had not taken them while on active adt ?


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5. I do read that there seems to be disagreements among the experts on some of the
start and stop and eligibility criteria mentioned above
and am asking here in context of wanting to try to get the latest view.

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6. Have read that some drs feel IADT should never happen if one is metastatic, others
differentiate between soft tissue metastases (allow iadt) vs bone ones (not
allow iadt), and so on.

for example, in the link below, under the dr comments tab, many say they do not believe
in iadt if metastatic, or only under very limited circumstances,
but they don't distinguish between lymph nodes and bones or other distant
areas. And its that point that I really want to understand since I am
metastatic.

http://www.researchtopractice.com/COCP15/5/Commentary2

Yet other articles or studies have mentioned iadt might be used in the
metastatic situation. (though again does not differentiate between bones and
other)

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7. Also, some studies have shown that iadt is worse related to finding
more heart/ischemic problems when one is on IADT than when on continuous ADT
(these findings were related to analysis of a certain other study that says patients on CADT
live longer than those on iadt.)

i.e. http://prostateforum.org/file/GTMD%20-%20Cancer_Network_-_Intermittent_ADT_Upped_Risk_for_Ischemic_Thrombotic_Events_-_2015-06-05%20%281%29.pdf


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8. If I was to summarize my main questions re the current view on IADT, they
would be;

a. does current thinking on IADT allow one who is metastatic in pelvic lymph node areas and not in
bones, and who who meets the other psa and T and other criteria - to be on IADT ?

c. what are the psa and T numbers used to start and restart ?

d. How long should one be on initial ADT before considering IADT ?

e. What should the nadir psa have been while on ADT and how long should that
nadir have happened before allowing IADT ?

Allen,

The original field did not include pelvic lymph nodes, but as per my earlier posts here on the topic that referred to some of your previous posts or articles, that is should the pelvic imrt be done or not, and
related to potential side effects of doing so, and your replies to those posts

as well as my 2 opinions from radiation oncologists on if pelvic and higher imrt should be done, which were taking into account the spread axumin found to also
the para-aortic area above the PLN - they felt the risk of adverse side effects would be too high,
and they recommended ADT only.

As to my post, yes I know its long but in past have been told at times that I did not provide
enough information, so wanted to make sure to do that.

BUT its important to me that you see my post and questions -
is there something I can do to make it more readable for you ?

===> Could you read and reply if applicable to just the last section of my post relating to me getting the latest views on should iadt be done for my situation -
and if so, about the criteria (especially relating to if someone is metastatic)

Here is that final section:

8. If I was to summarize my main questions re the current view on IADT, they
would be;

a. does current thinking on IADT allow one who is metastatic in pelvic lymph node areas and a bit above them, and not in
bones, and who who meets the other psa and T and other criteria - say that one can be on IADT ?

c. what are the psa and T numbers used to start and restart ?

d. How long should one be on initial ADT before considering IADT ?

e. What should the nadir psa have been while on ADT and how long should that
nadir have happened before allowing IADT ?


Thanks.

tomhw-

(a) All the trials I've seen on continuous vs intermittent show that outcomes are the same for men without distant metastases. I guess your para-aortic LN puts you in the M1a category, but you mostly seem to be N1M0. For those with distant mets (M1), they couldn't prove that iADT was not inferior to cADT. So it's really a judgment call, but I think most MOs would go with iADT for you.

(c) There is no one best protocol for iADT. It's whatever you and your MO agree upon. Usually the "on cycle" period is 7 months - a year (Assuming your ADT gets your T down to castrate levels, and your PSA responds accordingly). The "off cycle" period can be a set time period, until your PSA reaches some benchmark (eg, 10), until your PSADT gets very fast (eg 3 months), or until your T level gets back to a normal level so you actually feel like you've had a vacation. Again, it is a judgment call.

(d) iADT is often begun as soon as it is decided to pursue salvage ADT. It begins with the "on cycle" of course.

(e) There is no standard nadir to prove adequate PSA response to ADT. In the Hussain study, anyone was allowed whose PSA dropped below 4 after 7 months on ADT. It can be kept going until castration resistance sets in.

You didn't ask, but a nice twist on iADT is bipolar androgen therapy (BAT) - cycling 3 months on ADT with 3 months on high-dose testosterone. It assures that the vacation is a good one, and may extend the time one can stick with iADT. It's only been used in a small clinical trial.

/pcnrv.blogspot.com/2016/09/testosterone-to-treat-prostate-cancer_5.html

Allen,

Thanks for your post and the information.

I will look into the situation of the spread to para-aortic as being viewed
as distant.

As you mention, the results even for those with distant were "not inferior to cadt"
whereas the results for non distant were "same as cadt"

I guess I just was interested in iadt due to reading in general that it might

perhaps lessen some side effects and for me its the bone, cardio, anemia s/e
and other body systems that is important

and to perhaps delay the start of resistance, though I realize that might be controversial
(and am aware that most if not all studies that do say iadt can be good,, say it does
not reduce overall survival.

Thanks again.

Jerry, forgot to ask you - you mentioned doing the scans =am guessing you do the scans once psa had started to rise
while on iadt since only at that time the imaging would more valid due to imaging
not being that accurate at lower psa values ?

Where I live has axumin scan NaF bone scan, but not the choline or acetate or psma ones.
(I think the psma ones are still just in trials but will look to see if out commercially yet)

Jerry, thanks for replying about that. Am guessing you have some top notch drs
who helped analyze this, since most drs I think would not have people do scans when psa
was that low, due to scan accuracy issues. But it makes me think - how do others of us
know we are not also in that situation ? Don't know if this is a topic non expert pca drs
would know about.

Jerry,

I am interested in your Gleason score and the ADT drugs you have used. When you go back on ADT do plan to use the same ADT drugs that you have used in the past?

Thanks

Jerry mentioned on Xtandi and Firmagon for one cycle of IADT - I didn't realize that
Xtandi or Zytiga (with ADT) would be something that also could be part of IADT
(for someone still hormone sensitive)

I think thats cause I don't understand them well and also still have the view before more recent
studies that they were just for resistant situation.


As to combining therapies vs one at a time, have always been confused on the dr views
of that, for example ADT 1 vs ADT 2 or 3 - I'd read somewhere that drs at big institutions
or corporations did not like doing ADT 2 or 3, but the independents often did, but am probably
simplfying this too much here.

And I guess that its different for like ADT + Zytiga or Xtandi since I see that combination
in favor from academic or corporate drs, or at least am assuming so from all the many folks
reporting being on it.

mattamx

assuming one can do IADT when on adt + zytiga vs just adt, as per this post and Allen's comments
and lots of articles and studies, there is a lot of info there that could go into your question
of could a vacation even be considered

i'm still getting my head around that folks are doing adt +zytiga or xtandi as per recent studies
for hormone sensitive, (vs just ADT until resistance happens which i think was the way it had
been (and assuming still is -- or is everyone but me on just the ADT and not the zytiga or xtandi


as to the diffs between adt 1 or 2 or 3, I suggest browsing web, looking at the archives
here and/or making a post - since there are folks here who can explain that

My dr/institution/whatever, is one that does not do ADT 2 or 3 so I have not delved into it
as deeply as I would have.

When you stop the Lupron (if you stop) it takes a while to recover and your Testosterone to recover, so it's a slow process..By carefully observing how your PSA responds, you can decide when you need to go back on ADT..PSA doubling time is usually a good yardstick..