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Ok Terry, I shall try to expand on my recalcitrance to the use of intermittent ADT for early stage localised PCa.
As we all know ADT is widely deployed as a primary treatment of metastatic prostate cancer. It is also used to treat asymptomatic patients with PSA recurrence after failed primary therapy. Plus more recently as an adjuvant, and neo adjuvant, for locally advanced and localised PCa in combination with primary treatments of RP and EBRT. To my knowledge, albeit somewhat outdated these days, I do not know of any clinical setting where ADT is prescribed on an intermittent basis for localised PCa. Should other posters be of an alternative view, I should be most interested.
An abundance of research papers is supportive of the use ADT as outlined above. However it's use as a neo adjuvant for localised PCa is a tad contentious according to the literature. Bit of a worry, as that was the path I chose. So although effective, ADT is associated with multiple adverse effects, including vasomotor flushing, anaemia, fatigue, accelerated bone loss, increase fat mass, increase cholesterol and triglycerides, decrease insulin sensitivity, greater risks for fractures, diabetes and cardiovascular disease. The latter in particular was highlighted in a paper by Anthony D'Amico, Jim Denham et al, entitled, “The influence of androgen suppression therapy on the frequency and timing of fatal myocardial infarctions”. It makes for some sober reflection on my part.
Now my other reservation lie's in the indisputable fact, that testosterone is the fire the fuels prostate cancer. Thus it is not unreasonable to hypothesise that cycling on off periods of ADT may give rise to accelerated tumour growth whilst in the localised state. Only a series of trials would either support or refute that position, however I am somewhat uncertain as to the number of willing participants should such a trial be undertaken.
In Australia luteinizing hormone-releasing hormone agonists can only be prescribed for adenocarcinomas staged T2C or greater, although a bit of fudging does occur. Now as we know the ideal candidate for AS is a person with T1C or less, PSA <10, Gleason 6 (3+3). In my own case, my staging was T2b left side, but nearly palpable right side. PSA 6, Gleason 7 (4+3). Unlike you Terry, I was of the view, that left untreated, my PCa journey would end in 3 to 5 years time. I consulted widely on this issue and that was the consensus of opinion from my colleagues.
So in summary Terry, ADT has potential for decreased quality of life, cognitive and sexual dysfunction, hot flushes, endocrine abnormalities, cardiovascular disease, alterations in skeletal and body composition, all of which are commonly reported throughout the literature. In my view ADT is warranted when the benefits outweigh the risks based on available scientific evidence. ADT is a big gun in the medical arsenal Terry, but in time it's efficacy deteriorates into a hormone refractory state as we all know. Currently there is also considerable debate as to the efficacy of continued, versus intermittent ADT as well. So is there a place for intermittent ADT for localised prostate cancer, perhaps maybe one day, when the side effects, and efficacy issues long term, are addressed.
Dr Robert Liebowitz, Compassionateoncology.com, treats patients with localized PC with ADT3. He has several papers posted on his website that gives patient's stats and cure rates, which are better or equal to most local treatments. Not advocating this but it is a great source of information.
I had a good look at his website and the publications contained therein. Dr Bob as he calls himself, indicates that he is a "prostate cancer subspecialist", whatever that is ( we have no such equivalent here in Australia). This fellow I feel is a bit of a maverick. He acknowledges non acceptance of his treatment modalities from mainstream conventional medecine. He is also highly critical conventional treatment modalities such as RP and EBRT. His website state's, Dr. Bob believes that for most men, “The best local therapy is systemic therapy.”
In 2001 Leibowitz published a parer in the Oncologist entitled, "Treatment of localised prostate cancer with intermittent triple androgen blockade: preliminary results in 110 consecutive patients. The abstract appears below.
Leibowitz RL, Tucker SJ.
Compassionate Oncology Medical Group, 2080 Century Park East, #601, Los Angeles, CA 90067, USA.
OBJECTIVES: To determine the effectiveness of triple androgen blockade as an alternative to watchful waiting, radical prostatectomy or radiation therapy in the management of patients with clinical stage T1 to T3 prostate cancer. METHODS: The records of 110 consecutive patients were retrospectively evaluated. Patients were treated with a three-drug androgen blockade regimen, consisting of a luteinizing hormone-releasing hormone agonist (leuprolide or goserelin) plus an antiandrogen (flutamide or bicalutamide) plus finasteride (a 5-alpha-reductase inhibitor), followed by finasteride maintenance therapy, as the sole intervention. All patients refused local therapy and had their prostates intact. Determinants of efficacy included serum prostate-specific antigen (PSA) levels and disease-specific survival. RESULTS: Patients were treated for a median of 13 months with triple androgen blockade. At baseline, mean PSA level was 13.2 +/- 1.2 ng/ml (range, 0.39-100 ng/ml), and mean Gleason score was 6.6 +/- 0.1 (range, 4-10). During treatment, PSA levels declined to < or =0.1 ng/ml in all patients, with a median time of 3 months. After a median follow-up of 36 months since initiation of treatment, PSA levels have remained stable in 105 of 110 patients (95.5%). At a median follow-up of 55 months (range, 38-125 months), the mean PSA level for the first 57 patients treated in this series is 1.88 +/- 0.1 (range, 0-11.0 ng/ml). Only 9 of 110 (8.1%) patients have a PSA level > or =4.0 ng/ml. To date, no patient has received a second cycle of hormone blockade. CONCLUSIONS: Although median follow-up is short, triple androgen blockade therapy followed by finasteride maintenance appears to be a promising alternative for the management of patients with clinically localized or locally advanced prostate cancer. Further study of this approach is warranted.
PMID: 11306729 [PubMed - indexed for MEDLINE]
In 2005 he concluded, “The War was over,” and Triple Hormone Blockade® as a legitimate primary treatment option for prostate cancer had won". And in 2008 again suggests, "We always rationalized that using Triple Hormone Blockade® as primary therapy for prostate cancer was so far ahead of its time that it threatened conventional concepts". And with reference to his previous study he suggests, "In our Compassionate Oncology series, only 0.48% of patients developed hormone resistance, and only 0.48% of patients died from prostate cancer".
Some feedback on Dr Bob and his methodology would be appreciated. His publications are here http://www.compassionateoncology.org/publications.html
They do make for some interesting reading.
“Dr Bob” Leibowitz created quite a stir in the Cyber PCa world at the turn of the century because of his views – and the way he stated them. At that time the best Internet Forum was one designated PHML which was run by Don Cooley (he still has a site at http://prostate-help.org/home.html) . There were only two or three forums at the time so there was a concentration of men and women on the sites, many of whom had a depth of knowledge that they were happy to share. Regrettably these discussion forums are a thing of the past and the archives were lost years ago when his ISP went bust.
A lot of what Dr Bob said made sense to me although I must confess that since I thought I was years away from having to deal with advanced prostate cancer, I did not follow the detail of the discussions fully. He was criticized heavily because he did not publish his results for years and when he did submit a paper – the one you quote – the design of the study was disparaged and analyzed to death to demonstrate that his claims were unreasonable. People were so keen on demolishing him that I had to wonder if he was onto something in what he was doing. Anyhow, the result of his foray into publishing seemed to have convinced him not to waste his time on that since he was busy enough without any further publicity. The main criticism I have seen leveled at him seems to revolve around the fact that his claims are not ‘provable’ – as you’d appreciate, the usual problem when dealing with the scientific approach.
I am sorry I haven’t responded before now to your excellent response of December 11 and would like to take that dialogue a bit further if you are interested in doing so.
Your first paragraph is a good summation of the current used of ADT and I agree with you when you say I do not know of any clinical setting where ADT is prescribed on an intermittent basis for localised PCa. – I believe there is not one – and that is the point I’m trying to make – should there be?
I agree too with your list of ADT side effects, although I am less worried than you are about the linkage of this therapy to heart and diabetic problems, but that’s really by the by, I think, because the majority of side effects are not permanent if the treatment is stopped or suspended and the heart/diabetes studies involved men who had been on continuous ADT for some time, as I recall. They also may have had immune systems damaged by previous therapies and may have been on therapies designated ADT2 or ADT3.
It seems that you may not be entirely convinced that intermittent ADT is a wise move if I interpret your Thus it is not unreasonable to hypothesise that cycling on off periods of ADT may give rise to accelerated tumour growth whilst in the localised state. correctly. Whilst agreeing that this view is not adequately dealt with in existing studies, it seems fair to say that there is some evidence that intermittent therapy does not give rise to accelerated growth. It is also true to say that the use of ADT in the circumstances outlined in your first paragraph has resulted in complete remission in some cases. Very few of these cases have been reported, but….no studies does not mean no results.
Dr Strum, in his responses on his P2P forum will often comment adversely on any concept of delay in attacking PCa, his contention being along the lines that, if you were facing an enemy in real life, you wouldn’t want to let the enemy call up their reserves, increase the size of their forces and get their troops surrounding you. It would be far wiser to attack before this organisation.
And that was really what I was proposing for discussion. Most men, when diagnosed today have very small, very low Gleason Score disease contained in the gland. Why not hit those cells immediately with what I have termed “ADT Lite” – Zoladex or Casodex 50 mg for a short period? If that therapy works as claimed – by denying the small tumour the fuel of dihydrotesterone (DHT) – surely most or all of the cells will 'die' and even if the tumour is not completely eradicated, the immune system might be able to cope with the remains and ‘clean up’ any aberrant cells as it does on a regular basis at present?
If this did not work, then it would be regarded as neo adjuvant treatment. As you say this subject is a tad contentious but, like so many contentious issues, those objecting loudest about the concept seem to be those with the most to lose.
I realise that there are probably very few doctors that would even consider this approach, but I’m not so sure that there wouldn’t be a queue of men who would volunteer for a trial. After all, they line up for ‘new’ treatments like HIFU and Cryotherapy which have the potential for doing a great deal more harm than “ADT Lite” .
Terry, I well recall the stir that Jim Denham caused when he introduced neo adjuvant ADT in combination with EBRT in the Rx of localised and locally advanced prostate cancer. However the TROG 96 trial, which he co authored, was able to demonstrate validity, that held up to academic scrutiny. Thus the authors were able to demonstrate considerable benefits both in disease free progression and overall survival.
So perhaps we need to ask ourselves what role did ADT play in the Rx process. In my own case there was demonstrated substantial tumour shrinkage, in the order of 50% over the period of 12 months or so, plus an 85% drop in my pre treatment PSA. But of course at the time there were trade off's , which we have discussed previously, and of course as we now know, increased risk for fatal myocardial infarction. So now in hindsight, would I make the same decision again? Probably yes.
Now a 50% or more tumour debulking whilst on ADT is commonplace and widely reported thouhgout the literature. But to my knowledge, I do not know of any papers reporting complete eradication with ADT. If say with a T1a tumour, a 50% debulking would result in a very small tumour, which as you suggest te immune system can mop up. But therein lies the problem. Whilst it is well documented that even in severely immunio compromised persons, the immune system still works to a degree, PCa cells do a superb job in in convincing the immune system that we are not the bad guys. Hence the considerable amount of research worldwide into turning on immune system cancer receptors. So at best, ADT provides a certain timeframe for PCa remission, which can vary widely among individuals. But then again it could be reasonably argued, so to,do primary treatments such as RP, EBRT, HIFU and the like. Not surprisingly then the likelihood of recurrence increases with time. You just have to live long enough.
So back to your your suggestion re short term ADT for localised PCa. I guess my biggest concern, in addition to the health issues previously discussed, would be the likelihood of premature hormone refractory prostate cancer and thus a shortening in the timeframe to desease progression. No doubt minds of vastly superior intellect to our's have already mulled over this issue. If your idea had merit, then methinks suitable research trials would have been forthcoming by now.
Just a couple of things - is The Emperor's New Clothes (Hans Christian Anderson) amongst the stories that Australian children are exposed to?
Have you ever read the story of how J Henry Fabre, the great French naturalist, conducted a most unusual experiment with some pine processionary caterpillars. These caterpillars blindly follow the one in front of them. Hence, the name. Fabre carefully arranged them in a circle around the rim of a flowerpot, so that the lead caterpillar actually touched the last one, making a complete circle. In the centre of the flowerpot he put pine needles, which is the food of the processionary caterpillar. The caterpillars started around this circular flowerpot.
Around and around they went, hour after hour, day after day, night after night. For seven full days and seven full nights, they went around the flowerpot. Finally, they dropped dead of starvation and exhaustion. With an abundance of food less than six inches away, they literally starved to death, because they confused activity with accomplishment.
Many people make the same mistake - they follow methods and procedures for no other reason than "It's always been done that way."
If you wan to check it out.... The Life of the Caterpillar, by J. Henri Fabre, 1916 THE PINE PROCESSIONARY: THE PROCESSION at http://www.ibiblio.org/eldritch/jhf/c03.html
Yes Terry I guess I am a bit of a stick in the mud for the tired and tested. Your caterpillar analogy, with apology to hans christian andersen of course, is akin with the concept of,'dare to be bold'. I guess you have aptly demonstrated that, in your chosen pathway for your PCa journey. But were it not for persons of a similar disposition as yourself, then stasis would be the norm. Suffice to say I admire your boldness, and I am content with my own. That big yellow stripe down my back of course, not withstanding. Cheers and my best wishes for the festive season.
John
Terry,
from your penultimate posts ; you wrote " what I have termed “ADT Lite” – Zoladex or Casodex 50 mg for a short period? If that therapy works as claimed – by denying the small tumour the fuel of dihydrotesterone (DHT) – surely most or all of the cells will 'die' and even if the tumour is not completely eradicated, the immune system might be able to cope with the remains and ‘clean up’ any aberrant cells as it does on a regular basis at present?"
Two points.
Those ( few ) medics who actually measure DHT levels comment that whilst on Zoladex, Casodex etc. that the DHT level often remains high i.e. around normal levels.
Secondly, is it not a problem that the immune system is fooled by P.Ca. cells into thinking they are just prostate cells & therefore does not always get to work on such cells ? And that is part of the problem in 'mopping up '. Even after surgery where only a few cells may have escaped the knife, for example.
I think what you say reflects the multi-faceted nature of diagnosis and treatment of PCa. There is not ONE DISEASE; there is not ONE APPROPRIATE TREATMENT. What I put up was an idea for discussion, not a recommendation for treatment, where I have no expertise.
So regarding your two good points:
1. I have no doubt that there will be variable DHT levels measured after the commencement of ADT, mainly because there can be signifcant differences in physiology between individuals. So that is an area where I would love to see more direct studies published - is there a long term difference between the men with lowered DHT levels and those whose DHT levels do not lower to the same extent.
2. The immune system question is a very difficult one to deal with. I know that the general view is that cancer cells are adept at disguising themselves, but some studies have shown that the immune system can sometimes 'crack' the disguise. There is also the point about how often the immune system might deal with abberrant cells before they are even diagnosed. Although spontaneous regression is recognised as a possibility, the probability for PCa hasn't been studied until now. I think one of the spin-offs from the AS studies may well demonstrate that while some - perhaps most - cases of PCa do progress (at variable speeds) some regress. If that is the case, then it will be the immune system that is at work.
Well, as the poster who started this fascinating discussion, can I thank you all for your contributions?
As luck would have it, I have two consultations -either side of Christmas -with people who's opinions I greatly respect: First David Bottomley of Leeds Institute of Oncology, and, later, Mark Emberton of HIFU fame at UCLH.
If you guys don't mind I'm going to put together an edited version of your posts and get their reaction. Whilst they're leading proponents of their therapies (brachytherapy and HIFU respectively) I think they're open-minded enough to look at ADT as AS as an option. I don't think I have updated my profile recently, so I will do that soon. The concern for me is that the most recent MRI showed more tumour than was first thought, and bilaterally. The largest tumour is also close to the edge of the capsule. So, on the one hand, this argues for radical therapy soon. On the other, because of the location of the tumour (in the apex) my chances of ED are higher than I would want.
As it happened (and completely without his knowledge) Terry analogy to cardiomyopathy getting a heart transplant as a first line of action proved precient. I do indeed have hypertrophic cardiomyopathy. My consultants recommended a focal ablation to address the atrial fibrillation that I suffer from. I resisted, and through diet, lifestyle and supplementation, I've reduced afib episodes to less than 5 a year - not enough to warrant a serious procedure (no matter what Tony Blair says!).
So, Terry's comment struck a chord, though I know PCa (G3+4, T2) is not the same as a heart condition which is more or less stable throughout your life.
Lenny's comment:
Lenny Hirsch
David learn about the disease. Look at Terry's and my stories just to name two. Do not let the cancer dominate you and do not be scared of it. Find a doctor who will work with you if you decide on AS. If neccessary you have many treatments to fall back on.
Is important, as, if I understand it, with intermittent ADT strategy, my options for HIFU or HDR Brachy are still open to me further down the line. During which time I will not have experienced ED, or other significant side effects. When you're a newly married 56 year-old, these things matter!
I'll let you know what the consultants have to say.
David you seem to have formed the view that ADT will not cause, "ED or other significant side effects", and that as you say, " when you're a newly married 56 year-old, these things matter!".
David quite simply ADT = "Chemical Castration". Perhaps Terry will be able to provide one on his little stories to elaborate further on all of the relationship issues that ADT can facilitate.
Terry we have discussed misinformation before, and you know I have strong views about the spreading of. Henceforth I shall no longer post on this forum. I should also be appreciative, if you would remove my posts in this thread as well.
John
Gee, John, what did I do on the misinformation front?
I have never said that ADT has no side effects, in fact I have repeatedly said that ALL treatments have side effects (the principle one of which is ED). On intermittent ADT, I have said that the side effects are minimised when in 'off' periods and I believe that to be generally true.
I am sorry that you have decided not to contribute, but regret I cannot remove your contributions to this, or any other individual threads. The options I have are to remove the entire thread or to leave the entire thread. Sorry.
I am in the process of writing up a piece covering side effects for all treatments which I will be linking to the Treatment Options page and will, of course, make the point that whilst on ADT there is not only loss of libido but also loss of erectile function in the majority of cases. Currently the relevant piece on HORMONE THERAPY says in part:
Reported side effects of hormone therapy are numerous but are usually, but not always, reversible if the treatment is stopped - these side effects are sometimes referred to as Androgen Deprivation Syndrome (linked), which results from lack of testosterone. One of the most serious - and some say, inevitable - results of hormone therapy is loss of bone mineral density or osteoporosis, which can result in fractures and/or collapse of spinal vertebrae. It can be treated/prevented IF the medic or his patient is aware of the risk. Regrettably far too many people in the medical world seem to be ignorant of the side effects of the drugs they prescribe, so the burden of tracking and education devolves upon the patient.
The principle side effects of of major concern to men are loss of libido and erectile function - this therapy is often referred to as "chemical castration" and men can and are labelled as eunuchs. Although little can be done about the effects of loss of libido and erectile function, this piece - Castrated, Emasculated, But Hardly Disempowered!(linked) might be useful for men concerned about emotional aspects of these issues.
If that is classified as 'misinformation' perhaps you'd be good enough to guide me as to what is missing? You can do this by e-mail if you are seriously intending not to post to this Forum again.
Terry ... no explanation necessary to Mr Bonneville.
Unfortunately opinions are often mistaken for misinformation. It's obvious to most of us that he simply cannot tolerate a differing opinion and that's too bad because I was thoroughly enjoying the discussion (well, the parts I understood anyway ... grin).
To Mr Bonneville (if you happen to check back) ... sorry to hear you're bowing out of this one. You were making some very good points.
I'm also sorry that Mr Bonneville has thrown his toys out of the pram. Let me say, categorically, that I have not been 'misinformed' by anything on this thread, or this board. Why? Firstly, because I'm a grown-up and I make my wn mind up. But secondly, and most importantly, because I wasn't talking about ED/ADT connection out of ignorance.
I've been taking ADT-lite (casodex 50mg) for 6 weeks now, and have no loss of libido (if you don't beleive me, ask my wife) nor have I - with the same help from Cialis as I've been taking for the past 2 years - any problem with function (again if you don't believe me, ask my wife)
So, it's not about being misinformed. We're all experiments of one, and I can truthfully say that. so far, casodex has not affected my sexual function or desire. That's my truth, it may not be others.
