Dr Chris Hiley, Head of Policy and Research, The Prostate Cancer Charity
Professor Paul Forster Chairman, The Prostate Cancer Charity
Professor Roger Kirby, Director of the Prostate Centre and Visiting Professor of Urology at George’s Hospital, London
Professor Malcolm Mason, Cancer Research Wales Professor of Clinical Oncology
Dr Chris Hiley: Now we can start with the evening session - the Symposium on the BAUS Guidelines for the care of men affected by metastatic prostate cancer. I would like to welcome you all this evening and hope you have had an interesting day, whether you have been working locally, or whether you have been attending the conference generally. This evening we are going to be hearing from the three gentlemen here on my left all of whom are Professors and we were just trying to work out what the collective noun was for professors.
On my left there is Professor Roger Kirby, who is going to talk to us about how the guidelines have been developed by BAUS, which is the British Association of Urological Surgeons, and he is himself a very eminent urological surgeon. Sitting in the middle is Paul Forster, who will be talking to us at the end of the presentation. He is the Chairman of The Prostate Cancer Charity, and he actually has prostate cancer, and he will be fielding questions and helping us work out how the BAUS guidelines can be used to support the care of men who have prostate cancer, and how you yourselves can make use of them ensuring that the care that you get matches those standards appropriately.
And at the end is a hero of mine, Professor Malcolm Mason who has stepped in with about ¾ hour notice to take part in this symposium, as a very able substitute for Professor Nick James who has been called away to Birmingham. So I hope you will be entertained this evening, interested this evening, and will take part in this evening’s procedures. Thank you very much. I will now hand over to Roger.
Professor Roger Kirby: Well thank you Chris. I am the one that is not Chris’s hero, sadly.
I am going to talk a little bit about how we put together these guidelines - by the way, they are available at the back, they are available on a green CD ROM. Green is the colour, of course, very nature friendly colour, and there is a small overview - and they are all there at the back, if you interested you can pick up one of those at the end.
Why did we put these guidelines together? What we were aiming to do with these guidelines is try and improve the quality of life of the sadly, very many patients, who develop metastatic prostate cancer. And why we chose metastatic prostate cancer rather than localised prostate cancer is that we didn’t think we would be able to put together guidelines on localised prostate cancer because it is so controversial. You’ve got HIFU, you’ve got surgery, you’ve got radiotherapy. Hopefully as the situation clarifies we will be able to do that. We thought that metastatic prostate cancer was probably more urgent and more feasible to do because what we really want to do is try and improve the management of the very many patients who present to us.
The point of this evening’s symposium is to try and maximise the benefits of the guidelines because there is not much point in putting together guidelines, hours and hours of work, costs about £100,000 to do, and there is not much point in doing all that unless we get them out there. I think that with them being new and this new interactive approach is a good way to do that.
Why did we do them? We tried to create a benchmark for medical care. When I was working at St George’s I remember we had patients in with spinal cord compression, a cue for metatstaic prostate cancer, and we had this huge debate - Should we have radiotherapy or get the surgeons in? Should we start hormone therapy with something like Zoladex? Should we use Prostax? Should we use Casodex? Should we do a bi-lateral didectamy because it would have made it quicker, hormonal response? And no-one actually knew the answer to that, and yet this was somebody’s father.
So we needed to standardise care because in this sort of situation, where men have a serious disease - obviously a serious disease, metastatic prostate cancer in the bones - they need to make sure they are being managed in a standardised way and the doctors and nurses are not just making it up as they go along. So we did a formal assessment of the evidence base and we tried to promote the concept that any decisions that were going to be made about the patient would be based on the evidence but made in discussion with the patient. And not just with the patient but with the patient’s family. You could even say supporters actually, because a lot of the patients come with a sort of extended family. We posed the question - If significant departures from the national guidelines were being undertaken, then the patient might be able to get a second opinion.
My mobile phone went off on the way here, and it was a patient of mine asking about his daughter who has got a tumour of the pancreas and they were asking me questions about what was the best way to treat this, which I don’t really know. I don’t really deal with the pancreas. But I recommended that they call Cancerbackup and the charities, so that they get an independent view. These days patients want the reassurance that the care is being undertaken in a way that fits in with the general policy, and producing guidelines is a good way of achieving that.
What are guidelines? Are they rules? No. Are they protocols? Yes. Are they optional? Yes, because all these things are done after a conversation with the patient and their supporters.
Are they mandatory? No. Are they advice to doctors? Well they sort of are. One of the problems with guidelines, and my brother is a GP and he tells me when he gets into work in the morning he finds his pile of guidelines this high, because you have the Hypertension Society, the Diabetic Society, the Parkinson’s Society etc etc - they are all producing guidelines. And the problem for the GP is how do they digest these? I mean they need the information, but there is this “information overload”. What we tried to do with these is produce them in a relatively simple way that specialists, specialist nurses, GPs and patients could all understand. And you can be the judge rather than me, about whether we succeeded or not.
A few words about why we did it and what they are. Prostate cancer, as we have heard all day today, is the most common cancer in men. And it most commonly metastasises to bone, along with some other tumours such as breast cancer, kidney cancer, adrenal cancer, lung cancer. But when a tumour metastasises to bone it causes specific problems in the bone and being diagnosed with metastatic prostate cancer is a devastating thing. A point of these guidelines was not only to emphasise how to treat these patients with metastatic disease but also how to support them with better counselling than they were getting before which was perhaps suboptimal.
And we tried to emphasise that quality of life is a fundamental issue. If you are dealing with men with metastatic prostate cancer, most often they have to have hormone treatments which involve loss of sexual drive and loss of erections and basically a very negative effect on their sex life. And this form of treatment is initiated so often in these men without proper discussion about how it is going to effect not only them but their relationships and their partner. And I guess one of the other things we were trying to suggest with these guidelines is that much more discussion should be made before this irreversible step - sometimes if you do surgery, but not irreversible if its medication - that more attention should be paid to the psychological, social and spiritual well-being of men right through to the palliative phase, if and when the hormone therapy and the chemotherapy fails.
What are the consequences of bone metastases? Well, they result in the thinning of the bone and the weakening of the bone and this results in what we call skeletal related events, including bone pain and fractures of, say the femur or the pelvis or other long bones and perhaps most devastating, spinal cord compression like the patient I mentioned at St George’s, Sarah will remember, the patient when he came in, with localised pain in the back, sudden loss of mobility in the lower limbs and acute spinal cord compression, which needs urgent treatment, if its treated urgently and correctly you can get that patient walking again. If treatment is delayed they may be paralysed forever, so it is a clear example of the importance of getting the treatment right and handling the case in the correct way, which the guidelines hopefully will help.
That is just a slide to illustrate what bone metastases do; they result in what we call osteoclaysis, an osteoclas is a cell that eats away at the bone and bone metastases produces thinning and weakening of bone and sometimes those results in the spine, in compression of the spine and pressure on the spinal cord in the spine and this acute loss of power and sensation in the lower limbs.
Skeletal related events, as said, can result in loss of independence, and I think that is an important thing. We came up with this algorithm: Patients with hormone resistant prostate cancer which are either symptomatic or asymptomatic. I won’t go through all the limbs of the algorithm, but what we tried to produce in the guidelines was a number of algorithms such as this one, one for initiation for denoboe cases of metastatic prostate cancer, and also one for patients requiring palliative care or chemotherapy. It is just a number of options that doctors could think about and discuss with the patients and their family.
In this disease some people that I treat, say listen, my sex life is so much more important than the length of my life, I just want to avoid treatment altogether. Or some say I would rather go for the anti-androgen that preserves my sex life, but maybe doesn’t manage the metastases quite as well as the injection treatment that takes the sex life away completely. And again with palliative care, do they want chemotherapy, don’t they want chemotherapy? I think this is something that the patient needs to be involved in and the family supporters need to be involved in. So as well as putting together the pure evidence on what is best, some of this evidence is imperfect. One of the emphases was that more discussion, more involvement, more patient power should be involved in looking after these very many patients who present with this rather severe form of prostate cancer.
So I am going to hand over now to Chris’s hero, over to you.
Professor Malcolm Mason: That just has to be the best build up I have ever had in my life, I will come here again. Thanks Chris.
Unlike Roger I am not a surgeon, I am an oncologist. So I deal mainly with radiotherapy and with drug therapy. A huge amount of my work is looking after patients with metastatic prostate cancer. It is a very difficult and a devastating condition and we desperately need better forms of treatment.
One of the many hats I wear is in trying to get some uniformity in cancer services in Wales where I am based, I am based Cardiff. And I come to the view that if you can do just one thing and only one thing, I think it would be to get all of cancer services sorted out so that things happen in the right way, things are properly resourced, patients had the right treatments, they were managed the right way, they had all the right discussions, I think that would be the single thing that would make more difference than anything else to our patients.
Having said that I can’t possibly pretend to have made these slides even at 45 minutes notice, so I will do the best I can to do justice to them. But I was involved in the BAUS guidelines so I know a little bit about it. These are the four key recommendations in terms of the treatments and I am going to say a little bit about each of them.
Radiotherapy is one, and I will explain why in a minute. Orthopaedic interventions is another, surgical treatment with orthopaedics. Analgesics, analgesics are painkillers, and the fourth area is bisphosphonate therapy, we have mentioned bisphosphonates a little bit earlier on today, and I will say a bit more when I get to it.
Firstly, radiotherapy. You have heard about radiotherapy, you’ve heard about external beam radiotherapy, you have heard about brachytherapy. Well it is an incredibly important treatment actually for patients who have metastatic disease affecting the bone. Why? Because one of the major complications of bone metastases is pain. They are extremely painful, the reasons why are not absolutely clear. It’s actually quite complex, it’s a lot more complex than people realise. And radiotherapy is incredibly good at making that better, it’s very good, and that can be given as external beam radiotherapy, exactly the same machinery and exactly the same set up as is used when you are treating somebody who has prostate cancer, when it is just confined to the prostate with radiotherapy, but at a much lower dose. In fact it can be given in a single treatment and that is very important, because what that means is that in principle there are very few patients who are not suitable and not able to have that form of therapy. So it is a very important message which we as oncologists are always trying to get over to other colleagues, to patients, that this is really effective, it’s really worthwhile. And the provision has to be there to give it properly.
You can also give radiotherapy by injection and that is in the form of radioisotope, and I mentioned Strontium 89 earlier. It is extremely effective. And it’s particularly useful in patients who have pain, not in one place but have pain in a number of different places, which would make it more complicated to give external beam radiotherapy. Sometimes, and it really is only sometimes, patients do extremely well after Strontium 89, and I said and this is anecdotes, and you know that you should never believe anecdotes, well number one never believe anecdotes and number two never believe an anecdote that is told to you by an oncologist. If it comes from a surgeon, it’s different of course.
But recently, well not recently about 18 months ago, I treated a patient who had bone metastases with Strontium 89, we were having great difficulties sorting out his pain in any other way. To my surprise his PSA went down from 400 down to less than 1 and it stayed down at less than 1 for 18 months. Now that’s an anecdote. It is true, that is uncommon, but there are patients who get really quite a lot of benefit from Strontium 89. Which is why I actually feel it’s awful that is not used more in the UK. Why isn’t it not used more? Because it is difficult to know how to resource it. When we first started off having Strontium 89 available in our centre, do you know what the argument was about? It was money, but it was down to the level of is this a drug? Or is it a radioisotope? Because if it’s a radioisotope it comes out of the nuclear medicine budget, oh no its not, it’s a drug because it goes to pharmacy and pharmacy make it. But yes is money at the end of the day.
Now orthopaedics. Now it is rare for me to want to sing the praises of surgeons, but orthopaedic surgeons in this context are extremely important. There are incidentally an awful lot of medical jokes about orthopaedic surgeons, but I don’t think I have got time.
Why is it important? It is very important for a number of the settings that you have here; firstly if patients have a fracture, or if they are threatening to have a fracture, one of the things that bone metastases can do is to weaken the bone and if it is at all possible to prevent a fracture that is hugely important. So having an opinion from an orthopaedic colleague who can actually go in and stabilise the bone and prevent that fracture is crucial. It can be even more than crucial because in patients, and Roger has mentioned spinal cord compression which is a truly devastating condition and having good access to orthopaedic surgery to stabilise the spine can make all the difference. But it is not suitable for everybody. Some patients for various reasons, and they may be technical reasons, just can not have the surgery, so it is important that the set up is there so that patients can be assessed quickly and competently and its back to multi-disciplinary teams, it is a different sort of MDT setting. Very important.
Analgesics were the third. Now this is what is known in the trade as an analgesic ladder. It is known as a World Health Organisation Analgesic Ladder, I think, if I am reading it correctly it looks very much like it. The idea behind it was to get away from sort of completely random way in which analgesics used to be prescribed and to make it much more rational, so that patients could have their level of pain assessed and then they could be started either on a very weak analgesic like paracetamol, which I tend to find if it’s the morning after the night before can be a jolly weak analgesic.
Very often for patients it’s the right way to start, and then if you need to go onto a stronger analgesic than that there are weak opiodes so called and then finally on to opiodes, like morphine and morphine derivatives. There are some very important things about that and actually it is very important that this is communicated the right way to patients because patients still remember things about morphine. "You want me to have morphine? Does that mean I am on the way out? " Well it may not do, in the case of prostate cancer who can have a very long and very slow progression of their disease, so its very important that the right drug is chosen, it is very important that it is communicated in the right way. Also because actually giving opiodes correctly really needs the help of the patients, it is the patient who knows how much pain they have, and also there is no standard dose that is going to be right for every patient, so time is needed to really go through this properly.
Now changing the subject a little bit and just before we get onto bisphosphonates, how do we as professionals think about the complications of metastatic disease, and this is overwhelmingly bone disease? And Roger has mentioned this concept SRE, Skeletal Related Events, and actually we know that after the diagnosis, this diagnosis of metastases, the first SRE will occur about 10 months later and that could be a fracture, fracture’s matter, they matter of course from the point of view of quality of life because a fracture that is due to metastatic disease it is called a pathological fracture and it means that it happens just spontaneously or after minimal trauma or minimal stress as opposed to the sort of fracture that you get from skiing or whatever. And they do matter, obviously because they are painful, but they matter also because they do shorten survival, so its worth preventing them.
The next thing is that if we can possibly delay the progression of disease we would love to be able to do that. It is one of the most difficult things to achieve in this disease overall but it is extremely worthwhile and we should be using any effective treatment that can do that.
And so preventing complications should really therefore be one of the main goals in managing our patients and that is surely going to be the best ways of maintaining somebody’s quality of life. Why wait for the complications if we can actually prevent them, that is by far and away the best thing.
So these are the goals of treatment, ideally to delay progression of disease. Unfortunately it is extremely difficult and usually it is impossible to cure it at the stage at which it is metastatic. So that is number one. Secondly effective palliation of symptoms, and one of the things which has got, I will say, has got oncologists fairly exercised about the current debate about physician associated suicide, is that all too often in the oncology setting at any rate, requests for physician associated suicide usually means that there has not been very good palliation of symptoms. And by far the preferred option is good palliative care. And then thirdly to delay disease complications. So we need to be able to manage bone metastases in such a way as to improve or maintain quality of life, and to reduce the morbidity.
That is where the interesting bisphosphonate therapy comes in because there is evidence suggesting that giving bisphosphonate therapy early before patients have had a complication, might reduce the risk of them having SREs, or delay them. Even if you can’t prevent them, it is worth delaying them because might delay them quite a long time, and that might mean relieving bone pain or preventing it, reducing the number of fractures patients get and as I say, prolonging the time until they get it.
Fortunately I can’t read the management algorithm from there, I hope you can, but I think the important thing is to see how all of these things fit together and in particular, one of the things which does not happen currently with patients with prostate cancer, though it does happen with some other cancers, is that once they have disease in bone we think about bisphosphonate therapy, and the most potent bisphosphonate around is zolodronic acid, and that is the one on which the evidence is based.
So, implementing guidelines. There are challenges. A lot of these areas are already kind of well established, not so much the treatments themselves but the whole mechanisms, the infrastructure, the way patients are managed, the referral routes and so forth. So you have got to break into that if you are going to change it. Bisphosphonates in prostate cancer really are new compared to breast cancer, which is on the slide, and I would add multiple myolona, those are two examples of types of cancer where they are used absolutely routinely in every patient. And this does need a mind set change, its taking time, but the analogy with breast cancer is an important one, and I think this has been a theme that has been coming up several times over the course of the day that somehow, and several people have said to me and I believe it myself, we are today where breast cancer was 10 or 15 years ago.
If you went back in time, you would have had the same problem. Multi-disciplinary teams either didn’t exist or were just coming together, shortage of specialist nurses, were patients getting adequate information about things? Were they being involved in choices about treatment? It is a very real analogy, and in the case of breast cancer there is a very clear statement in the NICE guidance on breast cancer, this is the cancer service delivery guidance, which says as you can see it there; basically a very positive statement. At the moment we don’t have a statement of similar strength for prostate cancer. But I think in general terms prostate cancer patients have every right to expect the same level of interest, the same level of attention as breast cancer patients have, I think that message has got back pretty strongly to the politicians as well, I hope so.
So in terms of the BAUS guidelines on bisphosphonates, the plea is for earlier treatment rather than later treatment, not only to treat established complications – SREs - but to reduce the risk or to delay progression to a subsequent SRE. And I think this is something which needs to be debated with patients, patients need to know about it.
With that I am going to hand over to Paul. Thank you.
Professor Paul Forster: BAUS invited Chris and I to contribute at the later stages of the development of these guidelines of metastatic prostate cancer putting in a patient perspective to them. I remember sitting in the first meeting there and a very eminent orthopaedic surgeon brought up at least a dozen slides. Now as I said this morning I have had prostate cancer for about 6 years, but thank the Lord I have not yet got SREs or bone metastases. I think they are most horrendous twelve looking slides I have seen in my life, and I thought; do I really want to be here? It is not a pleasant stage of life to reach unless you have got very high quality care and that is obviously the point of the BAUS guidelines. We have heard all day, in various respects, about patient choice and what does it really mean when you put it in the context of this stage of prostate cancer? Well I guess generically, it could be said to be what is on that slide: the use and benefits of all treatments including bisphosphonates should be discussed and considered with all men.
Now you couldn’t really argue with that, but if you get more specific about it, what do men really want? Well they certainly want the quality and depth of information, that again we have touched on many times today, in all context of prostate cancer treatments. They want to know what sort of options are open to them and particularly at this stage that is critical because there are no easy answers. They want their voice to be heard and their opinion to be heard and they want to understand not just the pros but also the cons of the various option routes. They want to know how and in what way their physical symptoms can be managed to a degree that is both acceptable to them, and also is consistent with the consultant who is treating them.
Now that is fine too, but actually that covers up and disguises really a much more complex problem for the clinician which is that not all men want to take on board the same amount of information. Not all men are able to take on board the same amount of information. Indeed some men, not necessarily the majority, just want to be told what is going to be for them. So the real dilemma underneath this generic “can’t argue with that” statement about the quality and nature of information is to also understand the individual and how much the individual wants and can cope with, when you get to these very, very complex stages of clinical care.
Over and above that, the consultant often faces some quite significant dilemmas. He may well be aware of a treatment, a new and emerging treatment, that may be particularly beneficial for this particular patient in their particular context, but it may be for all sorts of reasons, good or bad, that that particular Trust or that particular Strategic Health Authority hasn’t yet sanctioned that particular treatment, that particular drug. I guess a good example, I am not sure it might have changed recently, would be bisphosphonates in Scotland. Certainly there is a great deal of distress caused by men in Scotland who couldn’t get treatment when people just across the border were having treatment. And there are many others that could be in this context. I guess you might be able to put the multi-disciplinary team resource into this context.
Whilst the Centres of Excellence may well have now very developed multi-disciplinary teams, it may well be out in the far flung corners of a Strategic Health Authority that that same resource isn’t easily available. What happens? What should the consultant say if the patient says, where are these multi-disciplinary resources I have read about in the BAUS guidelines? So there are a whole series of dilemmas that need to be faced, and I guess the only answer to that is to face them openly and transparently with the patient. And if you are going to bring the patients’ perspective on all of this to some conclusions, I guess they could probably be brought under these four headings. At this stage in this particular context of prostate cancer, it is fundamentally about the quality of life, it’s paramount.
The BAUS guidelines, we do believe, set high and appropriate benchmarks for the management of metastatic prostate cancer. The real crunch is how and how quickly will they be implemented? And I think one of the biggest issues perhaps to take out of this session is that since the implementation isn’t absolutely mandatory and isn’t necessarily therefore a rule per se, the patient pressure to have the implementation appropriately and swiftly in their area is going to be as great and probably greater than any other pressure. And the role of individual patients and their supporters can be absolutely fundamental to ensuring that these guidelines are put into practice by every consultant dealing with this condition.
So those are just the slides that we had for trying to bring a patient perspective into this session. I now, according to Chris, am ordered to put on my Richard Dimbleby hat to facilitate the “any question” stage of the proceedings. I do actually have one planted question to kick off the thing, in fact since the multi-disciplinary resource has been featured consistently through the day in many respects, I guess it would be a reasonable question to ask Roger, who isn’t of course the favourite here today, how can the patient tell whether he is getting the full benefit of a multi-disciplinary resource, and if he senses he is not getting that resource what does he do about it?
Professor Roger Kirby: That is a good question. The way that MDT’s tend to work, is that they are mainly deployed when a new diagnosis of cancer is made. So in that situation most patients treated in the NHS do get an MDT discussion. But the problem with metastatic prostate cancer is that develops during the patient journey through prostate cancer, so it wouldn’t be at all unusual for their case not to be discussed when bone metastases formed or when pain occurred as a result of bone metastases or even a fracture occurred. The only way you could tell in by asking and it wouldn’t be too surprising if they answer came back as no, we haven’t discussed this case.
Professor Paul Forster: What does he do then?
Professor Roger Kirby: It would be within the rights for him or the family to ask for that type of discussion, or to ask for a second opinion, or to go the GP and ask them. I think the more and more patients I see now ask for second , third fourth, fifth opinions, its quite common to do that. I think its part of patient empowerment, and in order to be empowered you have to have the knowledge and information and I think that is why it is important that people are aware of these new treatment possibilities.
Professor Paul Forster: Ok, thank you. Questions, could you just say who are briefly, and whether you are a man with prostate cancer or whatever your role is?
Audience: My father died at the age of 70 in 1989. He was first diagnosed with prostate cancer a year and half before that, it had already spread to the bones. He had the best possible treatment, he was in the States, and he had the best treatment one could have in that era. As a matter of interest, supposing all this had happened 17 years later, would he have lived much longer, with the advances over the past 17 years?
Professor Malcolm Mason: We are getting some very good questions tonight, it is a difficult one to answer. I think, of course, several things might have been different this time. The diagnosis might have been made earlier, so he may well not have presented with metastatic disease. That is something which is very rarely seen in the US today and in the UK, Roger will know the figures better than I, the proportion of patients newly diagnosed with prostate cancer who have metastatic disease at the outset is dramatically falling, falling quite substantially. So that may well have been different and it might have been picked up quite a lot sooner. Now if you said from the time point from which he developed symptomatic bone metastases, have things changed? Probably not hugely.
There have been incremental changes, but you know that seems to be the way things are happening with a lot of cancer treatments, that there are number of relatively small incremental changes which in themselves do not look that impressive, but it is when you gradually put the whole lot together, that it adds up to something big. And I will give you one example of that outside of prostate cancer; leukaemia. Now the treatment of acute leukaemia used to be uniformly dismal. I remember it well because if was my first job after qualifying, I was working on a leukaemia ward, and it was very difficult.
What happened? Gradually, gradually, gradually, with clinical trials survival rates had been nudged up so now, although there is still a long way to go, compared to the situation as it was then, 20 something years ago, it is vastly different. And I think that may well be the case with prostate cancer. It may be that we are going to get something fantastic and it’ll make a dramatic difference, and that could happen and I am very struck with what has happened with Herceptin agivant treatment for breast cancer, and we may well see something happen with that, or we may see a more modest incremental change over the years, over a long period of time.
Audience: Hi my name is Penny. I am sitting between two men who both have metastatic prostate cancer. One is my husband, one I met on The Prostate Cancer Charity website support group. Andy, my husband, was diagnosed a year ago with a PSA of 2,612, a Gleeson score of 9, with metastases throughout his body but with no bone pain whatsoever. Graham was diagnosed at 450 and does have bone pain, however neither of these men have been offered Zometa. I have asked for it but we were told it wasn’t appropriate at the time, and Graham didn’t know anything about it. So clearly something is going on here that isn’t right.
Secondly I would just like to say about the leukaemia that I believe there is a leukaemia database collecting information on all the patients with leukaemia surely there should be a similar thing for people with prostate cancer. And maybe that is why that leukaemia figures are so great and prostate cancer’s are so poor.
Professor Roger Kirby: Zometa, we know from a randomised study published by SAR about 2003, improves the outlook for men with delayed skeletal related events but doesn’t actually improve survival. So that is one of the reasons why not every Trust and certainly Scotland where there is the biggest argument about whether it should be offered as standard treatment. So that is the source of the debate. But I think there is really good strong evidence that the delay in skeletal related events such as spinal cord compression or pathological fracture, or even the development of pain, and there is a suggestion that Zometa, since it is usually pretty well tolerated, has to be given every three weeks usually by infusion, but it is well tolerated sometimes you get a flu like feeling for a day or so after but even that is quite uncommon. It should be offered as an option for patients I think and the information should be there.
That comes back to Paul’s point about multi-disciplinary meetings and the oncologists who deal with ladies with breast cancer are so used to using bisphosphonates, isn’t that right Malcolm?
Professor Malcolm Mason: That is absolutely right, and can I say something absolutely honest about problems which I think are going to face us increasingly, and that is management of high cost drugs in the NHS. In our Centre we are fortunate we can use these things, we may have to justify them. It is becoming harder to that because the budget is fixed. And I have to say, very often and increasingly it is going to come down to a decision by, in England it is called a Primary Health Trust, in Wales they are Local Health Boards and they will be the ones who will make the decision about whether they will or will not fund a particular treatment. It is not only treatment its investigations, PET scanning is another example and honestly that is half of the problem.
Audience: They should have advice though, it’s up to you what you choose to do, maybe we will choose to fund it ourselves, but if we are not given the choice we don’t know.
Professor Malcolm Mason: I think what I am trying to say is to echo Paul’s point that I think in the next few years I think that the patients voice is going to become increasingly more important in this.
Professor Paul Forster: Take one of the printed documents and take one of the green discs and go along and say; what have you got to say about that? And good luck.
Audience: I am a research sister. There is actually a clinical trial into bisphosphonates and radiotherapy for bone pain. As far as I am aware, none of the bisphosphonates specifically within the BNF, are licensed for prostate cancer and I think that is where the problem is they are not actually licensed for prostate cancer specifically.
Professor Roger Kirby: Not quite right, Zometa, zoladronic acid is for metastatic prostate cancer which has escaped hormonal control where the PSA is rising right now. We think actually that it might be useful before that, but I think right now the license, I think I am right in saying.
Professor Malcolm Mason: Yes I think the license is for metastatic bone disease. You are absolutely right there is a trial, I think it is a randomization between radiotherapy and a bisphosphonate for bone pain. I think, what you are talking about is the whole issue of getting a man while he is healthy and whether they should be given bisphophonates?
There may be a refinement to this, which I think could be important, which is making a judgement based on looking at what is happening in individual men, back to the old saying that all men are different. There are some men that because you can measure what is happening in the bone, you can measure bone turn over, by looking at either break down product in the blood or in the urine, it may be possible to identify men who particularly should have treatment, and maybe there are categories of men who might benefit rather less from treatment. I think that is a whole area for research and that is one step further on from the basic premise that these things should be available. Incidentally, in the NICE guidance in 2002, I can’t remember the exact wording but it is wording to the effect that bisphosphonates should be considered, or something like that, so that should suggest that it should be discussed at the very least.
Audience: That wasn’t my question anyway. My question is - are clinical trials a treatment option or are they an additional activity in your point of view?
Professor Malcolm Mason: Sorry I am heroically hogging the microphone here. I strongly believe they are a treatment option, I would say that because I am a clinical trialist. People have always that that clinical trials are a “good” thing to do. They are good things to do from an altruistic point of view, increasing the knowledge base helping the patients of the future.
They are actually good for patients of the present because oddly enough there is now evidence that if you look at the survival of patients who are in a clinical trial it seems to be better than the patients who are not in a clinical trial. And that bears no relation to whether the thing that is being studied in the trial was actually beneficial or not. It is all to do with the fact that if they are in a clinical trial they have access to people like yourself, the research nurses, they are treated according to protocol which reflects best practice, and all of these other options are things which would be considered by the trial committee and would therefore be taken account of and I think it is those sorts of things.
Audience: I sadly just lost my husband with prostate cancer. He was only 56 and had metastases into his bones. He was very fortunate to have Strontium 89. We had meetings with oncologists and having researched as much as we could about the disease, we were able to discuss, and were fortunate enough to have it, and he also had Zometa which again was a marvellous relief to his pain. So through discussion and research that we did ourselves we were able to have this treatment so perhaps now these guidelines are in place more people will be offered it as a matter of course, and without having to do an awful lot of research on your own.
Audience: You will know by my accent that I want to comment on the Scottish situation. I was involved, as was the President of our Support Groups Association in the past, to have the Scottish Medicines Consortium decision changed. We didn’t succeed in that but we have a good ally in Professor Alan Roger the Medical Director in the Beatson Institute. And he and staff put together a protocol advising his own consultants when and how to deliver zoladronic acid. Now that protocol managed to leak down to the support groups, and one or two of them wrote to their local consultant and said here is a copy of the Beatson protocol, please give it deep consideration when you are thinking about the treatment for a particular patient.
Professor Paul Forster: So it works. Thank you.
Audience: John Crowe, I have a relapsed prostate cancer following conforma radiation and hormone therapy, two years on. My PSA was rising rather rapidly in fact with a doubling rate of about three months so it was it wasn’t out of control but it was rising rapidly. Put back onto Casodex and the PSA been bought down to a level of 2.8 which is probably ok at the moment.
My dilemma is this, my oncologist has stated, that that is it mate, you are on hormones now and that would appear that that is my lot. However I have done a bit of research and looked into alternatives like cryo and HIFU and photodynamic and decided that I want to explore those possibilities. Hopefully if one of those is successful, it will give me another extension to life. Now, my dilemma is that I don’t know who to speak to about it. I have spoken to various eminent people today who have given me advice. One of them has said that I should perhaps have a word with Professor Kirby with regards to a salvage prostatectomy, another one has said go for HIFU. I am confused, basically. And I don’t know what to do or who to speak to about it. If I go to my oncologist he will probably give me five or ten minutes and won’t get to the bottom of what I really want to know.
Professor Roger Kirby: Well, it’s difficult to give you specific advice now without a bit more information, and its slightly off the subject because it is not metastatic, which is of course, good news for you. The reason that there is confusion is that we don’t have the evidence yet of which one these treatments is likely to be effective in the long term, and there is a risk with secondary treatment after radiotherapy of actually making the patients worse. Cryotherapy can cause fistulae, radical prostatectomy can cause incontinence, and HIFU, such a new treatment, quite attractive in a way and not available in many NHS outfits apart from UCL Middlesex. It might be worth talking to Mark Emberton at UCL and getting an opinion from him about HIFU. HIFU does have an appeal in that situation, certainly wouldn’t do much harm, does have to be given with an anaesthetic over a two or three hour period, might be quite promising in that situation.
Professor Paul Forster: I fear I have to draw it to a close, as they have got to clear the building. Can I ask you to thank our two eminent clinicians for their frank answers? Hope you have enjoyed the day and I hope we will see you next year in some form, in some place and good luck.