I was just wondering, I heard dr. Richard Joel Wassersug Saying that ADT works well and better if you continue with it but if you start and stop, start and stop, it doesn’t work as well. Did all of you from your own experiences found this to be the case based on your experiences? Thanks for any feedback.
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ADT working mechanism
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Ahk1
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How can anyone answer that from their own experience? How would they know what would have happened if it had been used continuously?
True statement
ok. How about RCT then?
The SWOG-S9346 trial found that intermittent ADT had 10% greater mortality than continuous ADT (90% CI: -1% - 23%).
Because I'm considering BAT, I followed up on this post with my oncologist and asked about the SWOG-S9346 trial. He noted that the authors of the article in NEJM acknowledge, "Our findings were statistically inconclusive." (nejm.org/doi/full/10.1056/N.... Although there was a higher mortality of patients receiving intermittent therapy in this study, the differences were not large enough to ensure they weren't just caused by chance. He stated that there have been many other studies of this and his overall conclusion is that the average mortality rate is about the same either way.
Not exactly. The results were statistically inconclusive because the authors had pre-set a level of 20% increase in mortality as the benchmark level at which they would be justified in calling iADT as inferior to cADT. IADT caused a 10% increase in mortality, which was below the benchmark. However the confidence interval ranged from -1% to +23%, so they could not rule out that mortality was worse than the benchmark. That's why it was "statistically" inconclusive, although patients should take the 10% increase in mortality seriously. Whether that increase is enough to justify intermittent ADT is for each patient to decide for himself.
He is also incorrect that many other studies in this population show they are about the same. SWOG-S9346 was the largest study ever done on this topic in this mHSPC population.
Perfectly expressed TA. 👍I had exact same thoughts but hadn’t yet put them to words.
Ten-year-old trial. New U.S. government registered trials are focusing on Zytiga and Xtandi.
nejm.org/doi/full/10.1056/N...
As I read through the results, I find negatives and positives for continuous vs. intermittent approaches and note that we are not able to conclude superiority or inferiority. PSA trigger level was 4.0-20.0 ng/ml. Would they get similar inconclusive results if they used a more stringent PSA criterion?
"Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651"
"95% CI, 0.97 to 1.25). The proportional-hazards assumption was not violated for this model (P=0.25)"
C vs cont/intermittent ADT
That has been my experience. Ten years and six months continually on Zoladex and the last eight and a half years on Zoladex and either Xtandi (enzalutamide), Firmagon (one year) and more recently Zytiga (abiraterone). No breaks.
I looked at your bio. Did you have any RT at all? Thank you
Hello,
I have not yet been on chemotherapy but I did initially (2013) have radiation therapy on my back and neck. The radiation on my back was for pain mitigation and went reasonably well. The radiation on my neck was a different story. For two weeks everything I ate had to go through a blender. During that time I was unable to swallow food. Eventually my swallowing reflex came back and now my radiation experience is just a distant memory.
Very glad to hear your good results. Sounds like a rough go, but worth it. My husband had very limited RT. HDR Brachytherapy only. So it's good to see you've had such success with only palliative RT. Always encouraging to see longterm success for advanced cases. Thanks for sharing
RCT: clinicaltrials.gov/study/NC...
pubmed.ncbi.nlm.nih.gov/248...
Moffit directed trial: moffitt.org/es/newsroom/new...
Multiple followup trials in progress.
thanks for posting, it looks like they might have a superior approach!
Various clinical trials are in progress for Xtandi and Zytiga adaptive therapies. This approach gathered interest and funding quickly. Hopefully the results are good and we might change our process. Embark was adaptive. Huge trial. Can't make many conclusions from it though. The others I've seen have control comparison arms.
Phase III trial of an adaptive therapy with excellent results. AUA 2023: EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-Risk Biochemically Recurrent Prostate Cancer
urotoday.com/conference-hig...
A Phase 1b Adaptive Androgen Deprivation Therapy Trial in Metastatic Castration Sensitive Prostate Cancer - PMC ncbi.nlm.nih.gov/pmc/articl...
Adaptive Abiraterone Therapy for Metastatic Castration Resistant Prostate Cancer - Full Text View - ClinicalTrials.gov classic.clinicaltrials.gov/...
Phase II Randomised Controlled Trial of Patient-specific Adaptive vs. Continuous Abiraterone or eNZalutamide in mCRPC - Full Text View - ClinicalTrials.gov clinicaltrials.gov/ct2/show...
From the second link provided by PCaWarrior:
Androgen deprivation therapy (ADT) has been the standard of care for metastatic prostate cancer for decades; however, the choice of continuous or intermittent administration is a matter of debate. Two large phase III trials have reported results comparing these 2 forms of ADT administration. The National Cancer Institute of Canada (NCIC) PR-7 trial studied men with an increasing prostate-specific antigen (PSA) level and no evidence of metastatic disease after definitive or salvage radiation therapy and radical prostatectomy. The Southwest Oncology Group 9346 trial studied men with newly diagnosed hormone-sensitive metastatic disease. The primary end point in both trials was overall survival with a noninferiority design. The NCIC trial showed that the overall survival in men treated with intermittent ADT was not inferior to that of men treated with continuous ADT, but the SWOG trial was inconclusive regarding noninferiority. Certain domains of quality of life were better in the intermittent arms of both trials. If using ADT in the setting of biochemical relapse, intermittent ADT should be strongly considered over continuous ADT, except perhaps in patients with Gleason score of 8 or higher. In men with metastatic disease, continuous ADT remains the standard of care, because the SWOG trial did not establish noninferiority of intermittent ADT with respect to survival. However, for those with significant side effects from ADT, establishing the risk group, as determined by PSA value after 7 months of ADT or the presence of pain at diagnosis, may help guide the choice of intermittent versus continuous ADT in men with metastatic disease.
This is why IADT v continuous is a controversy. It depends------on a lot of things. I remember several years ago when I was seen at Johns Hopkins with biochemical recurrence 4 years post op, the doc there said he wouldn't start ADT until "I have disease to treat", by which he meant metastases visible under standard scans, which I did not have, and still do not have 7 years later. I am now under the care of an MO at a leading cancer center, and at his recommendation I have been on vacation for 2 years and 7 months. Throughout that period PSA was always <0.01. But now (Nov. 2023) it is 0.3.
As TA has pointed out, my life expectancy is not knowable had I continued ADT, but that does not require the assumption, let alone conclusion, that my life has been shortened. What is knowable is the quality of my life for the last 2 1/2 years. No side effects, no expense, no frequent scans, injections, office waits, etc. Some might say I've stuck my head in the sand. OK, I like sand. I wonder how many of Dr. Wassersug's cohort have the SPOP mutation. And on and on.
I am now 2 months into my 83rd year, and when I'm old enough I plan to run for President.
Thx for sharing your experiences and especially for your last sentence. You’ve made me smile on this cold winter morning in Croatia.
😂😂😂😂😂. Love it.
do you have spop?
Yes, only mutation. I may be mistaken, but I think I saw somewhere that about 25% of PCA has this mutation. Was told by MO at MSK that SPOP is positive for progression but responds very favorably to ADT. So far, that has been my experience. Began ADT when PSA was 5.70. 1 month later PSA was <0.1. Never rose while on ADT or vacation, until now @ 0.3.
My only mutation also. Yes SPOP is very sensitive to ADT and has a favorable response/longevity profile as per every study I’ve read. Your response has been exceptionally good - did you precede your vacation with radiation or anything else “extra”?
I’ve also come to understand the following about SPOPmut, which you might already know:
— very sensitive to ADT
— possibly less responsive to BAT, PARP and immunotherapy
— associated with higher levels of methylation, thus possibly responsive to demethylation approaches; I’m using sulforaphane to address this angle.
— it appears to be a good responder to theranostic approaches
— SPOPmut PCa is known to generate lots of PSA (true for me, but I’m glad to hear not so much for you…what’s your secret sauce????)
BTW I’m also doing IADT + periodic PSMA scans to track progression. At this point, my scans show a reduction in total # of tumor spots over the last 8-10 years, in fact at the moment there’s only one spot showing up. Never any evidence on standard scans.
I wish us both the best of luck and continued success.
Thank you for your reply----your information is well beyond mine and I now have to consult Dr. Google to be better informed. Was on ADT for 1 year. No radiation or anything else before vacation. Only radiation was to prostate bed at first recurrence in 2016. Failed that radiation; PSA continued to rise. I don't have any secret sauce except possibly I chose my parents well. Taking no supplements except D3 and K2 (very low D-25 hydroxy) Maybe positive thinking works----I don't fret about PCa--- I have cancer but cancer doesn't have me, and I know I won't die from prostate cancer (although I don't approve of any of the other methods either). Doc has scheduled PSMA scan in Jan, and pending results, may suggest radiation to avid sites, if not too many (several years ago had 2 under G68 scan). Thank you again for your helpful reply. I'm going to follow you. All the best.
As you said, it's very individual. My PSA was <0.01 but, based on my case, every MO I talked to advised continuous ADT. After 3 1/2 months of ADT (I used estrogen patches similar to PATCH trial), I had severe sarcopenia (6' 4" and down to less than 150 lbs). My MO felt that ADT was more of a liability than it was therapeutic. So, I stopped and moved to BAT. That was 4 1/2 years ago.
So, had you gone of ADT immediately, you have no idea if you would have had severe CVD or diabetes or fractures. Some guys do great on ADT. Some of us aren't so lucky.
Be great if we could summon some clones and test things out before we try them. Of course, we'd have to fight the newly formed CRGs (clone right groups).
Complete opposite. I’ve been cycling it a year on — 7 to 10 months off for the last 4 1/2 years. I am still castrate sensitive.
Jan 2016 began Cypionate on-off-on-off---etc. even though GL10.
My husband was diagnosed (G3+4) and had a radical prostatectomy in 2001 at age 59 with positive lymph nodes. He completed 9 months of Lupron & Casodex and his PSA went from 1.0 to <.001 during the ADT. After stopping the ADT, he had labs every 3 months and PSA stayed undetectable until 2019. At that time he restarted on ADT & had Gamma knife treatment to nodes. He is now 81 yo. Until last year his PSA was ok. I wouldn’t trade the 18 years with no side effects for anything. QOL really matters. How long would he have lived if the therapy had been continuous? Who knows? But he still feels fine.
I suppose it comes down to how serious the side effects are for QOL. I am lucky in that the SE are managable but my impression is that the original PCa has been zapped by ADT - and its now dormant - and held inplace by continuous ADT. But at the beginning of castrate resistance I dont think the situation changes - its just that a new beast rears its ugly head - a castrate resistant form - which was quickly zapped by 160mg/day Xtandi and is now dormant and held in place by 80mg/day Xtandi. I think that both forms still reside in my body and a background regime in the blood that is unattractive to further growth is a good thing.
Thats the way I look at my PCa
I'm on ADT (Lupron at present) for life, year four, took a month off this past July, all okay, then unexpectedly had to skip in October due to illness, PSA rose from .9 to over 1 (1.2) for the first time in 4 years. Now I'm praying it will eventually go back down in a few months 🙏 I'd leave this one to the experts , your MO.
My QOL after 4 years on ADT was so bad that I would have gladly sat down and watched my last sunrise if not for having the responsibility of a family . I have gone down a different path and my psa has got to 0.064 from a high of 61, 18 months ago.Every one's journey is different, research research research . Cancer is a Wiley foe and there are many ways to reduce it, you just have to find the right path for you.
Which different path did you choose?
Firstly well done on your nu mbers. Would you share your different path it has to be something to bring that big psa drop.
My absolute turnaround was at Verita Life in Thailand. I had tried various other protocols with some limited success but the clinic in Thailand was my most successful. A combination of prescription off label drugs and natural meds . I don't think that I am cured, just ahead of the cancer for now.
this article seems quite thorough
ncbi.nlm.nih.gov/pmc/articl...
And this more recent discussion by Dr Hussain et al. urotoday.com/recent-abstrac...
Being on ADT is nice until it isn’t, as well not being on ADT is nice until it isn’t.
That being said I’m staying the course.
IADT is not recommended for APCa patients. Period. Full stop. I wonder why it keeps popping up on this APCa board. If one wants to stop their medicines, they are always free to do so. The Hydra cares not.
From your profile it appears your disease may be more aggressive than mine. I hope it isn't; best of luck and carry on.
it continues to come up because of studies referred to by mangycritter in his long post above, and by PCaWarrier in his Moffitt link, among others.
I have been on various treatment for 17 years. I had some off periods in the first ten years but more or less rapid disease recurrence has kept me on Xtandi mono for the last seven years. I had a PSMA scan in May and one spinal met found and radiated successfully. With best scan possible no other spread seen from head to hips. My M. O. believes in oligometastatic treatment and when I saw him last month I asked if I could now stop treatment with psa <.1.
He was ambiguous in his answer and said he would allow me to make that decision based on my concern about side effects of current treatment of which there are nearly none. I decided to reduce to one Xtandi a day from four to see if tiredness resolves and check psa every eight weeks and if a rise I will return to four per day.
For those who have troublesome side effects, more so than I, it may be an option but the long term results must be considered. Also I wanted to reduce the breast growth possibility of reinstating Xtandi in the months or years ahead if I were to stop now. My decision was based on a future certain side effect and not current ones, which are limited/minimal.
edit: This is an enlightening read on this thread and I thank the participants.
He may have said that at one point, but studies have shown that intermittent ADT is not inferior to continuous.
Sorry for being late getting in on this discussion. I casually watch the discussions of ADT on chat lists, but rarely post. However this growing thread starts with a posting that reports on something I said in a zoom meeting recently. So, I should respond.
The wording that Ahk1 uses to summarize what I said implies something a bit different than what I was trying to say. But subsequenting postings overall get it right.
Reference to the non-inferiority trial comparing continuous to intermittent ADT shows that intermittent ADT is not inferior to continuous ADT. But that is a statistical conclusion and, depending on one's overall health status, genetic risk factors, cancer burden etc. that is not the same as saying they are exactly the same in term of cancer control or survival. All things being equal, continuous ADT (as Tall_Allen notes) has a slight survival advantage.
So, starting with that fact, the pragmatic questions that I tend to focus on are, "If one elects to stay on ADT continuously, how can one have the best quality of life? How can one minimize the side effect burden of ADT other than avoid going on it or staying on?"
The research that my colleagues and I have published shows that patients have better self-efficacy in managing the side effects, if they know about them all and management strategies for handling them before they are hit with any of them. That was the genesis of the ADT Educational Program and the ADT book.
The book does discusses continuous versus intermittent ADT, but it doesn't endorse one over the other. It does though go into details about managing ADT side effects, which can help patients whether they are on it short or long term.
One important topic that I have not seen investigated is the impact of continuous versus intermittent ADT on the partners of us patients. The literature shows that ADT is not only emotional challenging for us patients, but also indirectly for our partners. I have never seen a study which asks, "Are we easier or worse to live with if we stay on ADT or cycle on it off it?" Any patients (or partners) want to comment on that? Does anyone think it is a question worthy of real objective research?
Richard Wassersug
I take it the zoom meeting was the AnCan one. I missed it but am waiting for it to come up in the archives.
Your comment about partners is an important one. They do not come up enough. I know my wife is severely impacted and is my lifeline. I think your question of is a study worthy and the answer is yes.
Has your ADT book been updated? I don't remember it discussing iADT vs cADT. But I read it several years ago so...
Thank you Dr. Wassersug. It's easy to overlook that we only spend a few hours a year in the clinic; the remainder is spent in the real world. I have no training whatsoever, but my initial thought is that such a study would be very difficult to design, and most likely would be anecdotal.
I am sorry dr. Richard if I misunderstood. Thanks for the clarification, sir.
It definitely is a question worth investigating. My husband started ADT in October 2018 and then had 37 sessions of RT . We thought that was it, but he was Gleason 9 locally advanced and in 2021 we discovered it had metastasised into his bones and he would be on ADT for life. The 3 monthly injections caused so much pain and abdominal discomfort that he opted for an orchiectomy instead. No more 3 monthly jabs- just Enzalutamide for the time being. The impact on our life as a couple is “the elephant in the room “ but nobody ever talks about that aspect. My understanding is that intermittent ADT is no better as far as sex drive goes - testosterone rarely returns to former levels.
Thank you Lenders.
I am surprised though that that you say about ADT " The impact on our life as a couple is “the elephant in the room “ but nobody ever talks about that aspect."
That impact is in fact discussed in detail in the ADT book. However patients and partners may need to tell their healthcare providers about this resource, if they are not pointed toward it by their healthcare providers. For a recent peer-reviewed reference endorsing this resource, see:
pubmed.ncbi.nlm.nih.gov/379...
That paper is freely available to anyone on the internet. It discusses managing the breadth of ADT side effects. Any patient can read it and also print it out for the attention of their oncologists.
Richard W.
We’re in the uk and psycho sexual counselling is not widely available. It’s been a case of just be grateful your partner is still alive - and I am. Eternally grateful and ever so sad 😞
I stopped taking Zoladex after about two years. My PSA had then been undetectable for a long time. I just wanted to feel normal again and did not tell my GP. About 6 months later PSA started rising and I resumed the injections. PSA dropped, but never went down to undetectable again. Coincident, I don't know
Dear gsun (et al.)
To answer you specific question about the ADT book, 3rd edition of the book came out earlier this year. And, "yes" it is greatly updated from earlier editions.
Also, for anyone reading this, I am a PhD type doctor, not an MD. I am on this list as PCa patient, NOT as a medical authority. Just so there is no confusion, I ask that folks avoid the "Dr." before my name. Richard is fine.
Richard W.
I think this question doesn't really have an answer. Every Single Case is different. Way to many variables to know.
Hi Rocketman1960,
Almost everything about the psychological impact of ADT can in theory be addressed with properly designed research. But the more variables there are, the larger the sample size has to be.
I agree with you that a study about whether it is better for the partners of us patients (and our partnerships) for us to be on continuous versus intermittent ADT (all else being equal) would require a large sample size because of the many possible variable. Right now I am just curious to know what patients and partners even think about the question.
It seems to me that there is a presumption that continuous versus intermittent ADT equally challenging to our parthners. But that is apresumption with no data that I know of to say one way or the other whether it is justified.
All of us on ADT should be aware that psychologicla burden of ADT is actcually greater on the partners of PCa patients than on the patients themselves. The first study that I know of to show that was published by folks from MSKCC in New York around a quarter of a century ago. So, if we have research on intermittent ADT undertake to consider whether intermittent is less of a burdening on PCa patients than continuous ADT, shouldn't we at least be wondering if it is also less burdensome on the partners of patients?
Thank you for lending your expertise to this discussion. In answer to your question, I’ve found that freedom from the SE’s of ADT, lupron plus bicalutamide from 11/15-11/17, and then lupron plus enzalutamide from 9/20-3/21 and lupron plus darolutamide from 3/21 to 10/22, have made an enormous difference in my mental health and general feeling of well being during the two holiday periods I’ve enjoyed. Eliminating extreme fatigue and other ADT related SE’s has resulted in a much better quality of life for me and my spouse. While these are subjective observations, in which my spouse concurs, its motivated us to travel more, spend more time with family and friends and enjoy life more once again. Each one of us is different, and the choices we make are personal, but as a 74 year old 37 year non-Hodgkins lymphoma survivor and 8.5 year oligometastic prostate cancer survivor, quality of life decisions have played a very important role in the treatment choices I’ve made, always with the advice of my MO guided by scientific data.
I think the burden of dying because we didn't use a known treatment is far more damaging. If you have a true partner, discuss openly and they lay out a course of treatment.
I respect your opinion but as you commented earlier in this discussion, “every single case is different” which is why each of us must assess the pros and cons of continuous versus intermittent ADT in light of our individual and family circumstances. I don’t believe the issue is of “not using a known treatment” but rather of deciding with one’s MO and family about how known treatments are to be administered in his individual case. In this regard, the Dana-Farber led phase II A-DREAM study, NCT05241860, may shed more light on this difficult question for men battling hormone sensitive metastic prostate cancer.
No doubt about it my friend. Good luck on your journey. Each and every road is different.
FYI
NOVEMBER 5, 2023.
This survey merely asked members how they feel about taking an ADT vacation.
86 No - VALID responses (55.5%)
69 Yes - VALID responses (44.5%)
155 Total VALID responses
Good Luck, Good Health and Good Humor.
j-o-h-n Sunday 11/05/2023 11:17 PM EST
Good Luck, Good Health and Good Humor.
j-o-h-n Sunday 12/03/2023 5:40 PM EST
IMHO it's like this. Use the treatment that gives you the best chance at long-term survival. If the side effects become truly onerous, discuss that with your doctor. A temporary reprieve might help a lot. Otherwise, it's impossible to answer your question.
I was intermittent for a few years then continuous until now. It always brought my PSA back to <0.1. The cancer cells subdivide and grow as the testosterone gets higher. I used to think my sexual ability would come back if I took breaks. But it didn't. So I'm still alive after over ten years, which is good. I don't think I can answer your question.
what marker did you use to restart meds after your holidays?
PSA
what value of PSA?
I used PSA at 6 as the sign to schedule Lupron, twice, after about 10-11 months. TThird time I went up to39. It was always in collaboration with oncologists. First and 2nd time RO guided me. Third time was with MO who retired, then my new MO put me continuous.
Thanks
You were metastatic from diagnosis. I was not metastatic until 3 years after RT, ten years ago. I believe my metastasis began due to biopsy, as the first sign of mets was on tailbone and rectum, area of biopsy penetration. Later mets showed up in lymph nodes on my back, then ribs, then on skull, then on neck lymph nodes. Latest I am down to one met in spine, which migrated over the years from back lymph node. I am self-treating with heat when I feel pain. Pain subsides, reoccurs after days or weeks, then I reapply heat. Also I self treat with lycopene. I drink V8 juice and lycopene pills daily. I also have had limited success with magnets, on lymph nodes. All my own efforts are complimentary to Lupron.
P.S. I am constantly researching for ways to rid myself of this monster. Latest studies seem to indicate that some supplements, including antioxidants and vitamins, can lead to proliferation or progression of the disease. You might read this:
cancer.gov/news-events/canc...
So you eliminated your Mets by means other than RT?
Yes, but in conjunction with Lupron. I believe it helps to catch them early. See my bio.
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