ADT "vacation" terminology questions - Advanced Prostate...

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ADT "vacation" terminology questions

Derf4223 profile image
44 Replies

I see a lot of posters here who say they do ADT "vacations."

Are there any circumstances when NCCN SoC indicate cessation or interruption of ADT and abi?

The term "vacation" implies an inevitable return to ADT. Do you wait for rising PSA or a fixed time to go by? What about when one has oligometastatic mHSPC?

How many posters here who are or were on ADT "vacations" did so by their own request or by MO's orders?

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Derf4223 profile image
Derf4223
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treedown profile image
treedown

It applies in the context of Intermittent ADT or iADT. The details are best with Dr but you stop ADT and restart when PSA hits a predetermined #. Hopefully in that time you T returns as close to your baseline as possible. That last part is different for everybody.

Tall_Allen profile image
Tall_Allen

It depends on your situation. But based on your profile, men in your situation (N1 M0) don't get vacations - that would be dangerous. Read this:

prostatecancer.news/2023/04...

Brysonal profile image
Brysonal in reply to Tall_Allen

I have been consulting with my two MOs for the last few months and due to speak to my London MO again next week. Extract from last months letter to my GP:

‘ We had a discussion about whether XXXX should at some stage stop his hormone therapy. For patients with metastatic disease, intermittent hormone therapy is an accepted treatment, having only minor, if any, inferiority in terms of survival compared to continuous endocrine treatment. The quality of life is of course very much better’

My Finland MO also is of the view intermittent hormone therapy would be an accepted treatment for me. Are they missing something I should flag?

Only difference between them is London MO says another 12 months would be better before a holiday but would support a decision to do it in July with very close monitoring.

Tall_Allen profile image
Tall_Allen in reply to Brysonal

"Are they missing something I should flag?" Yes, they are missing a lot. Please read this:

prostatecancer.news/2023/04...

Brysonal profile image
Brysonal in reply to Tall_Allen

I had read it and will print it for him and check which clinical trials he is basing his advice on. He is very experienced and evidence is his thing ( though happy to listen and has tolerated my add ins to SOC - now telling other patients about early Lu-177 overseas for example) I will also check it has gone through the MDT at UCLH. Thank you for the prompt response. I will report the source of his position on intermittent therapy being an accepted treatment due to only a minor difference in survival and an improvement in QOL.

I am also going to discuss the EMBARK trial results re the lutamide monotherapy arm. It seems to have performed unexpectedly well.

Tall_Allen profile image
Tall_Allen in reply to Brysonal

EMBARK used enzalutamide. The monotherapy arm did not perform as well as the combination:

prostatecancer.news/2023/05...

All men with metastases have to consider that SWOG-S9346 found that iADT increased mortality by 10% vs CADT.

Brysonal profile image
Brysonal in reply to Tall_Allen

I’m so not an expert but just read SWOG-S9346 was not statistically sound . You haven’t mentioned this:

sciencedirect.com/science/a...

is this not considered relevant? I am putting together info but appreciate I may be missing nuances of what counts as good science.

Tall_Allen profile image
Tall_Allen in reply to Brysonal

It was statistically sound, in fact, it was the most statistically sound (n=1,035) trial ever done on the subject. This gets into the weeds, but it was an "inferiority trial." For iADT to be judged non-inferior to cADT, they said in advance that it would have to increase the death rate by less than 20%. That was based on previous trials. But both groups, iADT and cADT, performed better than expected. It only increased the death rate by 10%. But the 90% confidence interval ranged from 1% better than cADT to 23% worse than cADT. The average was 10% worse. That makes it statistically "inconclusive." But from the patient's POV, he must deal with the result that mortality increased by 10% by using iADT. His actual results may be anywhere from 1% better to 23% worse.

Your link combined two groups: 68% were locally advanced (N1) and only 32% were metastatic (M1). N1 have significantly better prognosis than M1, so combining them confuses the outcome. In fact, N1 may be curable and would never get iADT under current SOC.

They also used cyproterone as part of their ADT. Cyproterone is not approved in the US because of the high rate of cardiovascular side effects. So, it is not surprising that they found: "The greater number of cancer deaths in the intermittent treatment arm (106 vs 84) was balanced by a greater number of cardiovascular deaths in the continuous arm (52 vs 41)." If they hadn't used cyproterone, iADT would probably have been distinctly inferior.

London441 profile image
London441 in reply to Tall_Allen

The mix of N1 and M1 patients-especially weighted toward N1-is confusing all right. Based on this it seems the M1’s could easily do even worse than 23%.

Still, it’s also easy to believe a lot of guys would gladly accept a 10 or even 20% increased risk, so appealing is the IADT concept.

The reality, as TA has pointed out in the past, is that vacations often don’t produce T recovery that is sufficient or lasts long enough before ADT needs to be resumed, and that vacations get shorter as the disease progresses.

Despite this, you will not find any shortage of men willing to do it.

Derf 4223, to this date I don’t imagine there are many MO’s ‘ordering’ IADT. IADT is patient driven. Drs are become more sensitized to the QOL issue, so they are generally more flexible than in the past, but some will still push back against it for sure.

The question of whether IADT keeps the disease ‘off balance’ is much discussed but clearly not enough is known. But again, it’s an area of keen interest. I recently talked to a friend of a MD family member who is a hematologist and MO at a well known center of excellence. He says efforts to replace/eliminate ADT are gaining a lot of momentum there. Of course this may not mean much yet but it is good to hear. Doctors have generally been indifferent about ADT QOL issues in the past.

As far as relief from side effects-overcoming fatigue, regaining muscle, losing fat etc-consistent and intense cardiovascular and strength training is the horse you don’t want to put after the cart. Looking to vacations alone for relief, or projecting a return to exercise once T returns and one ‘feels good enough’ is a common mistake. We are old, and more than ever before the time to exercise is now. T declines with age even in the healthiest men as it is.

Brysonal profile image
Brysonal in reply to Tall_Allen

I thought the ‘lutamide’ monotherapy arm of EMBARK outperformed the combo on QOL by some way? I’ve also read opinions that for some time SOC has undertreated mHSPCa at diagnosis but overtreated with ADT when under control.

Tall_Allen profile image
Tall_Allen in reply to Brysonal

It was not "lutamide," it was enzalutamide - a very specific anti-androgen. It does not apply to any other antiandrogen, whatever your fantasies may be. I showed you what it said. You can make up any fictions you want, but the facts are the facts.

Brysonal profile image
Brysonal in reply to Tall_Allen

Strong words for a simple discussion of the implications for the wider world PCa population of the results of the EMBARK trial (Phase 3 for Hormone Sensitive Prostate Cancer) having included an ARSI monotherapy arm *Enzalutamide' back in 2014.

The results of EMBARK has opened up much discussion among oncologists about the use of these types of drugs.

Enzalutamide was used but is one type of this class of drug and discussion of its use is grouped with abitaterone, apalutamide and daralutamide in much literature with a further sub division between:

- androgen synthesis inhibitor-abiraterone

- androgen receptor antagonists - enzalutamide, apalutamide, and darolutamide

My London onco calls them 'the lutamides' which seems a reasonably understandable abbreviation and their best use seems a reasonable discussion.

If you mean to advise that anybody considering a monotherapy discussion sticks to discussing Enzalutamide as evidence doesn't exist for the other two yet that is a good observation and I'll take it that's that what you mean.

Tall_Allen profile image
Tall_Allen in reply to Brysonal

"My London onco calls them 'the lutamides' which seems a reasonably understandable abbreviation and their best use seems a reasonable discussion." Then he is an idiot, and you might be better off with a different oncologist.. Nilutamide, flutamide, and bicalutamide are a completely different class of medicines from the second-generation antiandrogens like enzalutamide, apalutamide, and darolutamide.

The ENZAMET trial proved that:

ascopubs.org/doi/10.1200/JC...

Even those act differently from one another. Lumping them all together serves no purpose, and may do harm, if it leads you to believe they are all equivalent.

Brysonal profile image
Brysonal in reply to Tall_Allen

I won’t pass on that you think he’s an idiot as that would be rude of course.

Noted that we should always use the full terms;

The androgen receptor antagonists - enzalutamide, apalutamide, and darolutamide

Is calling them ‘the ARTa s’ an acceptable abbreviation though?

Justfor_ profile image
Justfor_ in reply to Brysonal

For once, I will admit that the person that claimed there is no PSADT bellow 0.1, later facelifting it to lack of validation, has a valid point in dividing lutamides into two leagues: Those still being under patent and selling for 100s of times more then their aging relatives. Your UK MO is a genuine "idiot of a doc" if he/she fails to realize the distinction.

Brysonal profile image
Brysonal in reply to Justfor_

Smiling.. definitely more than one way to divide things.

For me I consulted with 4 MOs on which ‘tablet’ to add in and was basically given choice of any of the 4. I didn’t want the prednisolone so that crossed Abiraterone off the list and left the ‘other tablets’ . Royal Marsden consult and Finland consult leant to Apalutamide do it got the vote. As BUPA were paying I didn’t even look into patents or costs tbh so far from an expert in this response. My ‘idiot’ MO from UCLH would have gone Abiraterone but respected I didn’t want the pred and prescribes Apalutamide. Nobody really gave me comparative data on these 4 let’s alone the ‘olds’ though Finland MO likes bicalutamide got intermittent hormone therapy., I really don’t want boobs tbh and am v pleased to have avoided ( radiation shots to breast buds in Finland and I’m a gym go-er) .

I do believe the science is coming tho. My dad died of PCa in 2016 having had SOC as was ( ADT monotherapy for 6 years and when he went resistant chemo gave him another year). I trusted the SOC and failed to research. No one mentioned the clinical trials that he could have joined on early chemo/ enza/ Abi/ radiotherapy to the prostate. All now proven and I’ll never know if I’d got him beyond SOC treatment what impact it would have had but the research released since shows the SOC from 2010-2016 in Uk for those diagnosed as advanced sucked!

fireandice123 profile image
fireandice123

I’m currently on vacation #3. I hope that it’ll be a permanent vacation but I’m quite aware that most likely I’ll be back on ADT at some point. My MO and I have no set PSA level when I end the vacation. Rather when my PSA starts to rise to around 1.0 from the nadir we’ll start having conversation about what to do and probably have more scans to see what’s going on before making any decisions. That’s been my experience for the previous 2 vacations.

I can’t say that my MO has ordered me to go on a vacation. But he does put it out there as an option when my PSA is quite low usually for at least 8 months (I typically have follow-ups every 4 months) and I make the decision. For my situation at least my MO is quite comfortable with me taking vacations.

maley2711 profile image
maley2711 in reply to fireandice123

are the vacations bringing you significant benefits?

fireandice123 profile image
fireandice123 in reply to maley2711

I feel significantly better while on a vacation. Hot flashes disappear. More energy. Less fatigue. Fewer aches. Clearer head. Better mood. Spontaneous erections without the help of Sildenafil. I feel more like my old self, albeit a 64 year old self so I grudgingly need to make concessions for that. Still can’t believe I’m 64. How did that happen???

Derf4223 profile image
Derf4223 in reply to fireandice123

So from your profile, each vacation ended with more met spots and a return to RT, ADT etc? Not sure that a vacation that returns back to Gitmo he11 doesn't average out to just sticking with LT ADT SE's. But what do I know? I'm not a doctor.

fireandice123 profile image
fireandice123 in reply to Derf4223

That’s a valid perspective. It’s not mine but it’s valid. My perspective is that if I’m in Gitmo and I can take a vacation away from Gitmo but will have to return at some point at least several months away I’m going to take it. At some point the option of a vacation won’t be available. Take it while I can.

j-o-h-n profile image
j-o-h-n in reply to fireandice123

"Still can’t believe I’m 64. How did that happen???" You must have said POOF!

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 05/18/2023 10:20 PM DST

dhccpa profile image
dhccpa in reply to fireandice123

How long did your two previous vacations last?

fireandice123 profile image
fireandice123 in reply to dhccpa

#1 was about 9 months and #2 was about a year.

maley2711 profile image
maley2711 in reply to fireandice123

wait till you hit 74 !!!

Concerned-wife profile image
Concerned-wife

Thanks all for the amazing discussion here. I just want to make sure you know of UroToday where you can read research and discussions from some of the leading physicians.

FYI my husband consulted with a leading prostate cancer physician and is on vacation ( de novo oligometastatic based on conventional imaging) the plan is for PSMA scan if/ when his PSA rises to 2.0

My understanding is that, because the original trial didn’t include one of the “ mide” drugs or radiation of prostate and mets, there is speculation that some men , who have been intensely treated upfront, might indeed benefit more from a vacation than those in the original trial

one example of info from UroToday

. urotoday.com/conference-hig...

pakb profile image
pakb

Not an option for my husband according to his oncology team- for the reasons Tall_Allen posted. Also- my husband doesn't feel his quality of life is suffering enough currently to warrant the stress he'd feel going off treatments that are working. He is active, working, enjoying life. I feel all of that has to be taken into consideration.

MateoBeach profile image
MateoBeach

Well you certainly got the info supporting cADT to consider. However, some individual men, including myself, suffer more harm and serious adverse SEs from ADT than others. I developed severe sarcopenia, spine degeneration, with depression, cognitive decline, etc. Just do not tolerate ADT. So I dropped continuous ADT. My testosterone did not recover so I started long cycle BAT 2 years ago. 3 months of very high testosterone then one month ADT with Orgovyx. It works splendidly so far. My head is clear. No depression. Muscles recovered and I feel great!

ADT increases mean (average) survival moderately while taking a toll on body, mind and QOL. But it also creates the conditions for the progression to castrate resistance. Average time is 18-24 months with wide variations.

I am still Oligometastatic (N1M0) HSPC, 15 years after diagnosis probably because I did not do long term cADT. I did do short term ADT, 6 months, adjuvant to SBRT to nodes identified on PSMA scan. Then followed this with Lu-J591, two doses in Australia. My PSA remains down 90% to 0.030 so far.

If you are oligometastatic N1 HSPC you should consider such a strategy with SBRT and SRT to the whole pelvis along with short term ADT (2-3 years and possibly with adding abiraterone) as possible curative therapy depending on what your scans show. Best hopes for you. Paul

TottenhamMan profile image
TottenhamMan

My Oncologist didn’t discuss an ADT vacation. She advised me that I had the best possible response to ADT and Radiation therapy and that she considered my course of treatment at an end after two years of ADT. My PSA and Testosterone were undetectable for a long period of time and she strongly advised cessation of Eligard. As she put it, she wanted to see if the cancer will declare itself. After an elapsed time of 6 months from termination of the Eligard injections, my PSA was still undetectable and my T increased to 4.0. She said that other than PSA tests every 3 months, we just watch and wait. If my PSA rises and gets close to 2.0, then we will move on to the next phase of treatment because a PSA of 2 indicates a possible BCR.

I do feel different after ending the ADT. My joints and muscles don’t ache as much and I feel a bit stronger. I even managed to walk 18 holes at the golf course for the first time since diagnosis. I still have hot flashes, and my libido HAS NOT returned, not that I expected it to.

Purple-Bike profile image
Purple-Bike

I am N1M1. With encouragement from MO I went on vacation after 10 months of ADT and five months of no evidence of disease,. 20 months later still that status, knock on wood. Vacation ends when I no longer meet his definition of remission.

My MO in Helsinki is probably the same as Brysonal's, will be interesting to hear his reaction to Brysonal's question.

Brysonal profile image
Brysonal in reply to Purple-Bike

Hi Purple-bike

If you use Docrates it’s v likely we do share an MO. In my most recent consult he said:

Hormone Therapy is not curative. B's disease has already been treated much more actively than generally has been the practice in ref studies.Continuous hormone treatment also increases the risk of castrate resistant disease. My experience is that it is possible to pause both chemical castration and apalutamide with the PSA and testosterone being monitored. PSA could increase slowly as testosterone recovers and any sign of disease progression will cause a re evaluation.’

He hasn’t failed to deliver on anything so far and I appreciate the bald statement of facts :

1. HT is not curative

2. There is no reference study that has had the combo of interventions that I have.

Very interested in following you.

Thanks B

Purple-Bike profile image
Purple-Bike in reply to Brysonal

Hello Brysonal,Right, Docrates, with Timo. He wants therapy effect to be measurable against evidence of disease. He was open to me quitting ADT (no other drug taken) already after six months, following spot radiation and no evidence of disease (but of course micrometastasis is there, as you say it is not curable).

Good to touch base with you.

Brysonal profile image
Brysonal in reply to Purple-Bike

Yes great to touch base and indeed we share an MO (although I am monitored with a monthly meeting by a London MO I still consult with Timo online). My ADT and Apalutamide are prescribed here in UK plus I participated in the OVM 200 Phase 1 vaccine trial here in the UK. Not curable but I really wanted to make sure i didn't leave things on the table that can help with the controlled position i am in atm.

Purple-Bike profile image
Purple-Bike in reply to Brysonal

Wow, you were in a cancer vaccine trial that includes PCa; I see from a press release that safety and immune response from this phase is deemed positive. On my part, the longer I am in remission, the better the odds that Timo's low-key approach is paying off in my case.

Brysonal profile image
Brysonal in reply to Purple-Bike

yes Timo and my London MO reviews the trial info and agreed it wouldn’t cause any problems re my PCa. I was number 12/12 to get the vaccine and no adverse effects in numbers 1-11 ( not sure I’d have been brave enough to be number 1 but that was a lady with ovarian cancer). The rats are doing OK also apparently! Same hospital trust as my London MO so he put me forward and as I am stable I met the criteria.

Yes it’s great being in remission and I am 100% aware the undetectable PSA could be all down to the ADT and Apalutamide. However NED on scans is a lot better than where I was in Dec 21 so I raise my glass to Timos plan ( and to wish for the OVM 200 vaccine trial to move to next phase. )

addicted2cycling profile image
addicted2cycling in reply to Brysonal

My ADT is not drug induced but instead by Castration, performed immediately upon diagnosis so there is never a vacation; however, my Dr. went against SOC and prescribed Cypionate (Testosterone in a vile) at 1mg/ml in bi-weekly injections that began 1 month post treatment and when PSA rises too high the *T* injections stop, a scan is done and a holiday from injections begins if nothing appears on the scans. When the PSA lowers I begin injections again, rinse and repeat. Just had my 3rd *T* injection today almost a year since I stopped due to a rise in PSA.

Brysonal profile image
Brysonal in reply to addicted2cycling

Very interesting approach. Thank you for sharing. I have read your profile with interest. SOC offers no cure so control and QOL has to be the focus doesn't it.

addicted2cycling profile image
addicted2cycling in reply to Brysonal

Quality of LIFE is what I've been striving for and my wife of 50 years in 2 weeks agrees, even if it ends my life sooner than later. We have talked about our eventual DEATH decades ago and have made every attempt to live as if the present day is the last.

Graham49 profile image
Graham49

Many thousands of men are living and dying on iADT and cADT yet the number of studies and the number of patients that took part is very small. It’s a case of big pharma not interested so little money from them for studies.

DennisCA profile image
DennisCA

I am now taking a vacation from Lupron, but not Darolutamide (Nubeqa). Dr. Rettig at UCLA/VA is my oncologist and suggested that I could take a vacation from both based on my current status (PSMA in deep remission). I was concerned about getting off both and said I would like to try mono-therapy with just Darolutamide. He said let's give it a try and if we find any mets we will first "zap" them. I also checked with my local urologist, who is a top guy in my area, and he said he agreed with stopping the Lupron shots, but that I should stay on the Darolutamide. I feel like a test case here, but we will see.

keys2life profile image
keys2life

After robotic radical surgery at age 59 and a G9 I was put on Lupron because of failure of the surgery to reduce psa to undetectable (1.37 three months post op)

Went off it a year later and psa stayed undetectable for about two years. I have since stayed on intermittent Lupron only, no other drugs or radiation, sometimes with a one year vacation, lately as short as three months. Currently on a six month vaca holding at .33

Been doing this for the past 14 years with about 6-8 on/off cycles and thoroughly enjoy my time off. Been using 1.5 as trigger to resume Lupron. All of this has been at my request with my onc reluctantly agreeing

Brysonal profile image
Brysonal in reply to keys2life

Really interesting to read and wow to 14 years. You you feel a QOL difference on the off cycles?

I will follow your story. Thank you for sharing.

GoBucks profile image
GoBucks

Check out this trial: clinicaltrials.gov/ct2/show...

I wrote about it and my med vacation about a month ago. So far, so good.

Brysonal profile image
Brysonal in reply to GoBucks

Thanks for this. Gosh 282 sites who don’t think it’s crazy to to interrupt hormone therapy in a controlled way if you’ve responded exceptionally well. Really interesting and seems to confirm some polarised opinions on this based on this thread!

I will follow you and read your story.

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