Admin Posted July 28, 2013 Share Posted July 28, 2013 Minutes: Advanced Prostate Group Meeting June 28 2013 These Minutes of the Teleconference are general in nature and not meant as advice. You must consult with Health Professionals for advice. Jim Marshall Welcomes Dr James Mackean Chairman Bruce Thank very much Jim. Chairman Bruce makes a special welcome to Dr James Mackean. Person #28: I can update you on what’s happened recently. I have had a bone scan and also an MRI which has shown cancer. It is quite significant in the sacrum and there are 3 ribs on one side and 4 on the other. Radiation is out. The oncologist suggests I go on Zometa treatment. He is claiming that may slow off the cancer in the bone area. At this stage I am getting some slight twinges of pain in the sacrum. I don’t know whether that is my back or the cancer. If I stretch it twinges in the right side of my ribs. I am back on hormone treatment as of a week ago. That is all they can do for me. I am back on Zoladex only. I am not taking Cosudex because it completely wiped me out on previous occasions, I couldn’t not drive, I became disorientated and not focused and like a zombie. I am not going any of that hormone treatment so it is just the Zoladex, we will see how I go. Chairman Bruce Regarding your teeth, have you had any checks on your teeth? Person #28: The oncologist wants me to go to the Dentist and have everything checked and give him a written statement to see that everything in my mouth is okay. I am a little bit concerned about this zometa treatment. I don’t know if there are any side effects apart from the gums. Chairman Bruce It only bothers the gums if it is going to bother anything, or at least running the risk of trouble with your gums. Person #22: I had zometa and hit me like a brick wall with exhaustion for about 24 hours after the course. You may get something like that. But it passes and you just need to go to bed and rest. Person #24: - I have been on zometa for 2 years to date and touch wood I got no side effects to date. Have your teeth and jaw checked you will be OK. Person #22: I would just mention one thing it was sorted prompted by a couple of the emails that Jim has sent out recently. There were two of them there earlier they claimed that reports at a conference about the potential benefit of being on Metformin which is normally given for diabetes and also for keeping your Vitamin D levels high. I have been doing both those things for the last couple of years and during that time my PSA was higher than I like but it has been stabilised at about 10-12 units. I am keeping the vitamin D at the top end of the normal range by taking vitamin D tables. I am also taking Metformin because I was diagnosed with type 2 diabetes. Since I have been keeping the vitamin D at the high end and also been on Metformin my PSA which was going up at a steady rate has now stabilised for the last couple of years. How long it will stay like that, whether it starts going down again or go up again I don’t know. I am a sample of one that sort of says what those said emails may have some validity. Person #28: There would be no point me taking Metformin because I don’t have diabetes? I wouldn’t do that would I? Person #22: No they probably wouldn’t prescribe it for you. I am not suggesting that Metformin is necessarily a treatment for prostate cancer but this thing that Jim sent out did sort of indicate maybe that it could be of some benefit if it your doctor had prescribed it for diabetes or pre-diabetes. Person #35: when you say the high end of vitamin D, what sort of figure are you talking 100 or 140? Person #22: About 100 or maybe a little bit over. A lot of people have low and I think that is down around 20-30-40. That is at the low end the high end is about 80-100. So I am sort of running at that. I take 2 normal vitamin D tablets which I have been on anyway and I take a calcium tablet each day and now I am taking 600 of the vitamin D. So that means I am taking 2600 units a day. Person #39: Just to be very clear although you can buy calcium and vitamin D at the shop it is not to be done by yourself. You should have your vitamin D measured by your doctor and if it is at the low end the doctor will put it up and monitoring it over a period of time because it does change. Again calcium often given at the same time as vitamin D but large amounts of calcium can kill your kidneys apparently. So be under medical advice for calcium and vitamin D. Person #22: I was put onto those by my specialist and my endocrinologist keeps track of what is going on with my vitamin D levels and calcium levels. Chairman Bruce – Should we now have Dr Mackean’s address? James we welcome you to this group of men who have advanced prostate cancer. Welcome and we are all ears. Warning! The transcript below was prepared from an unclear recording by someone with no medical knowledge whatever. Parts of it will certainly be wrong. Ask your doctor about anything that you read here. Dr James MacKean - Thank you for the opportunity of speaking with your group and I would like to congratulate you on the initiative and I think by sharing our stories in this way we can help each other. I have prepared some remarks about the potential role of radiotherapy in people with locally advanced metastatic prostate cancer. I will try and keep the remarks fairly broad. I thought it might be helpful to the group to provide some sort of historical background into why radiotherapy is often part of the treatment program for men with locally advanced or metastatic advanced prostate cancer and then to talk about some of the trial evidence behind that. Also the interest of members who may be interested in what is currently happening there are some new trials in this area that are recently reported which are ongoing at this time. If we’ve got some time and the interest we can spend some time talking about the specifics about radiotherapy, different types of radiotherapy, whether to use radiotherapy just to the prostate alone or whether to include wider treatment, newer types of delivery systems of radiotherapy, brachytherapy, high dose rate, the changing of the radiation dose of the radiotherapy. So the title of today’s talk is The Role of Prostate Radiotherapy in Men with Locally Advanced Prostate Cancer. The story goes back now about 20 years. We have known that with men with different types of patterns of prostate cancers what we should try and do is risk classification. When people are newly diagnosed with prostate cancer they have a number of tests and these tests help to find what patterns or grade of the cancer under the microscope. We are using such studies to try and work out whether it is just contained in the prostate or whether it is starting to grow through the capsule or whether there is any evidence of anything outside of the capsule of the prostate into a lymph node or a bone. Until quite recently our ability to look inside the prostate with imaging was quite poor. An ultrasound of the prostate really just tells us about the size of the prostate. CT scans similarly gives information about the size and shape of the prostate and you can look at lymph nodes in the pelvis. It doesn’t really tell us what is going on inside. Only more recently with the development of the newer technology MRI scans for the first time we are able to look inside the prostate and try and see whether there is just a small amount or whether there is a larger amount of involvement of the prostate. The MRI scan are being now used as part of the diagnostic work up for men newly diagnosed because it can also give information about whether there is spread outside of the capsule into the surrounding adjacent tissues, seminal vesicles or lymph nodes. I was quite sceptical about the potential role of MRI scans 5 years ago believing that the doctors chemical examination and the biopsy’s would give sufficient information on to base their decisions. My views have changed I think what we now need is a political push to have Medicare funding for MRI’s so that the costs of this procedure which is the main prohibiting factors with more wide spread use can be overcome. There are some men where MRI scans are not able to be performed if they’ve got cancer in their body or a pace maker. It is slightly an uncomfortable procedure where you are in a tunnel so it can be quite claustrophobic. Apart from that it is non-invasive way of looking at the prostate, no needles. The other thing that MRI is an advantage for it is relatively widely available now. That was not the case 5 or 10 years ago. The number of people who are being found with locally advanced or metastatic prostate cancer at the time of diagnosis has gradually reduced as a percentage of the total number of men being diagnosed. It still happens with sufficient frequency for many people to be found with this and so the large interest amongst doctors in developing strategies of treatment for men with locally advanced or metastatic prostate cancer at presentation. There is a large trial which is looking at the role of combined treatment with the landmark trial EORTC. That is the, European Organisation for Research and Treatment of Cancer 22863 which started in 1986. What they did was they took a group of men who had high risk locally advanced disease and 90% of the men in this trial had T3 or T4 cancer and they combined 3 years of hormonal therapy with something like Zoladex and it was given every 3 months for 3 years. It was given with radiotherapy. They compared it in a randomised way with just radiotherapy by itself and they followed the men in this large European trial for a median follow up of 9.1 years and they found that at 10 years the overall survival in the combination group of radiotherapy plus 3 years of hormone therapy was 68% compared to 40% of the radiotherapy only group. When they were analysing the results of this large trial the EORTC trial, despite the fact that the combined treatment was just a period of radiotherapy alone the value of the local treatment with radiotherapy remained under question as it was felt that the benefits might have been due to the early use of hormone therapy. This is a question that has been bandied around in the medical community for most of the last 15 to 20 years. How much of the benefit of combination hormone plus radiotherapy, how much of that benefit was from the hormone and how much of it was from the radiotherapy? So this is now being explored and answered in 3 randomised trials. The National Cancer Institute of Canada, MRC trial called UKQRO7 study randomised 1,205 men with high risk locally advanced disease to treatment with combined modality therapy that is radiotherapy plus androgen deprivation therapy or treatment with androgen deprivation therapy alone. This is testing whether the addition of radiotherapy improves results. They now follow men for a medium follow up of 6 years and the combined modality treatment resulted in a 23% reduction in overall mortality and a 46% reduction in disease for specific mortality and a 70% reduction in disease progression with the addition of radiotherapy. It also reduces the risk of the prostate being the first site of progression from 39% to 15%. They looked at the side effects of the radiotherapy and in the bigger scheme of things with the modest clinical magnitude and serious long term genital urinary or gastrointestinal toxicity in this trial was uncommon. So by the time 3 years of follow up were attained then the bowel and bladder walls were similar in the groups of men who had radiotherapy or who had not had radiotherapy. This large trial is now being backed up by 2 smaller trials similarly showing that the combination of radiotherapy and hormonal therapy for periods of just the hormone therapy by itself. These trials were started in the 1990’s and reported in the last 5 years. The dose of the radiotherapy that we use in these trials 65 to 70 gray represented the standard of care in the 1990’s when these trials were started. Over the past 15 years the development of new radiotherapy techniques has allowed for a considerable increase in the radiotherapy dose. When I started as a registrar 15 years ago the standard dose in NSW and QLD was about 65 gray in the year 2000 it was increased to 70 gray with the introduction of 3D informal radiotherapy. When we moved to 6 fields today compared to 4 fields it was able to be increased to 74 gray in about 2003, and since modulated radiotherapy 2008-2009 those doses have been able to be gradually increased to around 78 gray with acceptable side effects in terms of bowel and bladder function. There have been a number of clinical trials that have shown an improvement in local control and improved freedom from relapse with higher doses of radiation therapy. So much so for men with locally advanced or metastatic prostate cancer being treated with modern radiotherapy we generally think that it should give long term control in the prostate in approximately 90% or slightly higher so that the risk of progression in the prostate for men with modern radiotherapy should be less than 10%. So therefore it is likely the improvement of survival with traditional radiotherapy to hormonal therapy in these studies what would be more impressive is if we were able to use modern radiotherapy techniques in our patients. I think we are lucky in Australia that there has been a considerable investment in both the public and in the private radiotherapy centres in the introduction of modern radiotherapy technique. There shouldn’t really be any such thing as old fashioned radiotherapy in Australia. Also in radiotherapy centres in Australia and New Zealand there is also something called sub-specialisation, so that within that group of 5 or 6 doctors there is usually 1 or 2 doctors in a practice who have a special interest in prostate cancer. These doctors are more likely to be up to date with the modern technology and be able to offer this to their patients. So sub specialisation of radiotherapy for has also led to examination of modern radiotherapy techniques. I think it is now standard as care for men with locally advanced prostate cancer to be offered a combination of hormonal therapy and radiotherapy. The dilemma that still remain how long does the hormonal therapy continue for and how to deliver the radiotherapy and there are a variety of ways that can be done. The combination of hormone therapy and radiotherapy is better than either of them alone to men with locally advanced prostate cancer. What about the role of local radiotherapy in men who have metastatic disease at the time their diagnosed? Many patients presenting with metastatic prostate cancer are now asking their doctors whether they should have treatment to the prostate itself in addition to their hormone therapy. This question is increasingly common in the clinic. There is a growing sense that those enquiring patients may be onto to something. In fact there may be a benefit to treating the prostate primary even if there has already been evidence of something appear somewhere else in the body such as a bone or the lymph nodes. There are several lines of evidence that supports the testing of prostate radiotherapy in men with newly diagnosed metastatic disease. Most of the evidence does not come straight from prostate cancer but from another cancer which we see in the clinic. This is people diagnosed with cancer of the kidney or renal style cancer. Renal style cancer is thankfully not very common in our community. But because the kidney cancer can grow quite silently in over 25% of people diagnosed with kidney cancer there is already evidence of metastasis at the time that the kidney cancer was diagnosed. Our dilemma is to know this, what should the management of that kidney cancer be? Traditionally the management of kidney cancer that has metastasised is using systemic therapy. There are different ones, there is one Interferon Alpha and there is another one ... . There are a variety of different tablets or injection type therapies that have been used to prolong survival in men and women diagnosed with kidney cancer. The question that they were trying to answer in this was if I had also treatment to the kidney primary in which case removing the primary with a Nephrectomy (ED: kidney removal) do I do better or does leaving the primary tumour in place make any difference? So they have tried to answer this with 2 co-operative groups have run randomised trials of Radical Nephrectomy. The trials involved patients with previously untreated metastatic kidney cancer whose primary tumours were amenable to surgical reception and patients were randomised to either receive the standard systemic therapy of the day which was interferon alpha, either alone or with radical nephrectomy. Having the nephrectomy was shown to significantly improve median survival in both the trials. In one of the trials improved median survival from 7 months to 17 months more than doubled the survival and in the other trial from 8 months to 11 months. This was a really interesting. Finding the mechanism by which removing the primary tumour improves the survival remains uncertain. It is compatible with the theory that the primary tumour may be releasing factors that actually promote metastatic progression and if you remove the primary then you remove the endocrine factors that promote tumours and it may have protective effect by reducing the chances of new formation and growth with distant metastases. It has led to a theory of progression of metastatic disease called the ‘soil versus the seed’. What is the rationale for removing the primary tumour? In the case of prostate cancer treating the primary tumour with radiotherapy which should do the same thing when you give radiotherapy to the prostate your eradicating the cancer cells in the primary. You should be also turning off any chemicals or factors that are released by the primary. So what is this hypothesis about the soil and the seed? We do know that far from being merely the source of the metastases, the primary tumour also helps to prepare the soil. The primary tumour may give off seeds blown in the wind. Those seeds that circulate in tumour cells usually die. Only a small number of circulating tumour cells from tumours actually lodge somewhere else in the body and take hold. What is the role of the primary tumour in this process? If we believe the trials on kidney cancer then the kidney releasing chemicals into the blood stream might help prepare the soil. There have been a number of studies down showing that in order for a metastatic cell to lodge in for example a bone, the bone marrow cells has to make the local micro environment of the bone marrow more receptive to tumours cells for colonisation. It has been found that recruitment of cells from the marrow is stimulated by endocrine factors released by a primary tumour. The indication of this work is that therapy directed at the primary tumour by eliminating the endocrine or chemical signalling could retard the formation and growth of the distant metastases. This work has been sort of proof in principle shown in kidney cancer it is now starting to be applied to the thinking in other tumours. So this is the basis by which doctors working in the field of prostate cancer are looking at the role of definitive treatment to the prostate primary and the way of retarding the potential colonisation or formation and growth with the metastases. This is something which hasn’t been proven and that is the subject of a series of ongoing trials. There is a large trial which has been underway for a couple of years in the United Kingdom called the STAMPEDE trial (ED: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy). This is mainly being looked at for men with locally advanced or metastatic prostate cancer. They are newly diagnosed men with metastatic prostate cancer are randomised in this trial to hormonal therapy by itself and hormone therapy plus zometa. The thinking that the early use of the zometa might help protect bone and if we can protect bone that might have an anti-cancer action just by itself. This is the first trial which is actually looking at that. There is some work from an Australian trial called the RADAR Trial (ED: Randomised Androgen Deprivation and Radiotherapy) which I will talk about in a moment. Another randomisation is using hormone therapy plus chemotherapy Docetaxel (Taxotere) the combination of Docetaxel plus Zometa or the combination of hormone therapy and Abiraterone (Zytiga) and the new one being created in the STAMPEDE trial where there combining the hormone therapy with the radiotherapy. They are actively recruiting men in the United Kingdom from January 2013 and the aim is to accrue approximately 1,200 men and they are accruing well in this trial so far. They estimate that the accrual will be complete within 4 years of activation, that is before they end in 2016, with hopeful survival data available around 2018. ... The STAMPEDE trial may be regarded as a collection of studies in advanced prostate cancer within one protocol rather than a single trial in a conventional sense. The STAMPEDE trial management group have access to subsidiary projections from further comparisons that could be addressed either across the whole trial or in defined subtext as in this case. The original trial, in the STAMPEDE trial, was comparing hormonal therapy with chemotherapy. Hormonal therapy with Zometa or hormonal therapy with the two drugs combined. Those original trials arms in the STAMPEDE trial have all now successfully been completed. Their ... survival data expected in 2016. ... Some doctors are doing radiotherapy to the prostate primary in men newly diagnosed with prostate cancer before we have this evidence. The basic premise this is being done is that we can say to the men that the modern radiotherapy, if we do it carefully, with the image guidance and the gold seeds and if we do it carefully using the modern radiotherapy techniques then the modulated radiotherapy or RapidArc therapy now being widely available in just about all Australian centres we then can safely deliver local treatment to the prostate which should keep the prostate primary in part of the problem we can control long term in more than 90% of patients. It’s achievable now and is safe and if it reduces the risk of the cancer coming back in the prostate then it may be not unreasonable for doctors to offer this treatment whilst we await the randomised trial evidence that should be available from studies like the STAMPEDE trial in the next 4 to 5 years. If this generates discussion or questions I would be very happy to answer those questions. I would just like to talk very briefly about Zometa because this is quite topical it came up on the conversation at the beginning of this teleconference. The use of Zometa well established as a way of reducing bone pain and reducing the need for radiotherapy or painful bone and also for reducing the chances of having a fracture in both prostate cancer and other cancers such as breast cancer. It is clearly shown to reduce adverse skeletal events such as need for radiotherapy or such to help improve bone pain so we use the treatment for that. Interestingly in one of the other cancers that Zometa is widely used is Multiple Myeloma (ED: Kahler’s disease) which is a cancer of the bone marrow which tends to cause weakness in bone. There is some evidence suggestive that Zometa actually has some anti-cancer disease activity by turning off ... which absorbs bone. Does the Zometa reduce the ability of cancer cells to lodge and take hold in the bone? There is some provocative evidence in Multiple Myeloma that Zometa as well as being protective of bone and protective of the reduction in bone mineralisation and bone mineral density eventually caused by anti androgen deprivation therapy. Does it have any anti-cancer action as well? The use of Zometa incorporated in to part of the RADAR Trial which was a trial conducted in Australia and New Zealand radiotherapy centres in the early part of last decade and which is now finished accrual and is now in the follow up stage. The trial results have not been published but has presented in abstract form in the last six to twelve months in Australia and overseas. They randomised men in this trial to either the 6 months of hormonal therapy with Zoladex or carried on for another twelve to eighteen months. There was a secondary randomisation in the RADAR Trial where the men had Zometa once every 3 months during the time of the hormonal therapy or not. This is unpublished work. The graph of the groups who did or didn’t have Zometa seemed to be going parallel to each other. There doesn’t appear to be in these RADAR Trial men with localised or locally advanced prostate cancer, there didn’t seem to be any survival advantage or a progression free viable advantage from the use of Zometa. That doesn’t mean that there isn’t an anti-cancer effect it just means that it hasn’t been shown at this time. So at this time we think that the main role of Zometa is for men who are symptomatic from bone pain or who have evidence of progression of their bone condition on a bone scan or men who are using it to help reduce the reduction or prevent the reduction in their bone mineral density from the androgen deprivation therapy. It is provocative at this stage but it might actually have an anti-cancer action. It is something that ongoing trial, including the STAMPEDE trial are looking at. Are there any question? Person #40: On the point of the importance of beating the primary cancer even if it has spread. Did you say that you could have brachytherapy even though you’ve already have had radiation earlier? Dr McKean: - I did not get into the specifics of how we deliver that good local control into the prostate. It is usually done ... by external beam ... because brachytherapy is not available at all the radiotherapy centres - it is only available in some centres. Around the world most radiotherapy is given using external beam radiotherapy. Brachytherapy is just a way of modifying the giving of the dose from the inside usually men with locally advanced prostate cancer. If you are doing high dose rate brachytherapy about one third of the dose is done through the brachytherapy and two thirds is done from the outside. The modern external beam rate radiotherapy giving seventy eight gray with the gold seeds and IMRT should be at local control in the prostate by about 85% to 90%. Even the men with nasty types prostate cancer at the time of the diagnosis. Brachytherapy might be slightly better. It is still fairly much an open question. People who have had local radiotherapy with prostate cancer and their unlucky enough to be in the 10% or so who where it comes back in the prostate then yes brachytherapy can be given as a salvage treatment to eradicate any local recurrent. At the Wesley we have a salvage brachytherapy program for men with this condition. Only some men are good candidates for that where the cancer is only recurrent in the prostate itself and not anywhere else. It is another way of improving the long term control. The other thing we have not talked about is the role of surgery in locally advanced or metastatic prostate cancer. There isn’t a history of there being trials being done in this area because traditionally men with locally advanced or metastatic prostate cancer at presentation have not been recommended surgery. This is something that may be looked at in the future. The aim of surgery in that setting is again to try and remove the primary but the problem is that unfortunately if the primary is growing outside the capsule when they do the surgery then there is a very considerable risk of leaving microscopic cells behind. Then people have to go through radiotherapy at some point in time afterwards so then they potentially the side effects of both the surgery and the radiotherapy. That is a big thing that people have to put themselves through. Surgery is being looked at as a salvage treatment after the failure of local radiotherapy. It has quite a lot of problems with the risk of incontinence because you are operating in an area which has previously had radiotherapy and that often doesn’t heal very well. Using brachytherapy as a way of salvaging a local recurrent after external beam radiotherapy is an attractive alternative to surgery because it can be safely given without the risk of incontinence. Person #28: My radiation oncologist has suggested to me that seeing the cancer has spread into the bones there is no point to have radiation to the prostate gland itself because even with RapidArc therapy it will not help the ribs and as it has already spread he would only do spot radiation. What would your comment be on that? Dr MacKean: I think that your oncologist is correct in there at this time in 2013 there is no consensus amongst radiation oncologists that local radio therapy to the prostate is going to be advantageous in your case. What the trials have shown is, if you were offered radio therapy to the prostate it potentially reduces the chances of the cancer coming back or growing in the prostate primary. If I can just quote from the people with locally advanced prostate cancer from that randomised trial that I showed you we then meet and follow up in about five and a half years. The use of radio therapy plus the hormone therapy improves local regional control in the primary from 70% to 90%. So just doing the hormone therapy by itself will keep your prostate small in about more than two thirds, 70% of the time. If you add the radiotherapy to that then it increases the chances to your prostate will remain small to 90%. So there is clear evidence it would improve the local regional control but I can’t say to you it is going to make you live longer. So if we don’t use radiotherapy in your case and we use the hormone therapy alone as has been suggested by your doctors then 70% of the time you are going to be fine and if you were unlucky enough for the cancer to come back in the prostate or start to grow then radiotherapy can be given at that time. So the question is there a benefit to using it as a part of the initial management as opposed to holding back on it and just using it in those people who are unlucky enough for it to start to grow again in the prostate itself. That is where the dilemma is for the doctors. It is open discussions that patients are having with their doctors. So when I see somebody like you what I try to do is to have this discussion. I think at some point in time if the hormone therapy is not working so well so in 5,8,10 or 12 years when one is not getting as much benefit from the hormone therapy as before and the doctors are talking about chemotherapy to that person then the chemotherapy is usually very effective due to a response in the metastases in the bones and sometimes in the lymph nodes as well. The variable thing with chemotherapy in my experience, and this is anecdotal, in my experience when people have had chemotherapy and they have an uncontrolled primary, that is the cancer is active in the prostate again, because the hormone therapy is not working so well in the prostate primary and it has started to grow again. In my experience then the chemotherapy is not particularly effective in controlling and shrinking the prostate primary and it can become a difficult management problem. Sometimes people have bleeding or they have obstructive symptoms. While these sorts of things are uncommon but they sort of stick in the memory a bit. If the patient’s initial management has been a radical prostatectomy or radiotherapy and the primary site removed or controlled then that is one less potential problems that people can face when there has been chemotherapy for their reoccurrence castrate resistant prostate cancer. Attitudes are gradually changing and part of what is generating the debate and discussion between the doctors and their patients. First of all with modern radiotherapy people can be confident they are going to come through it as happy customers, they are going to have good bowel control and good bladder control and they are not going to be damaged by the radiotherapy, with modern radiotherapy techniques. People are living longer with combination hormonal therapy ... so that people are living longer with their aggressive metastatic prostate cancer long enough to benefit from the primary site being removed or radiated. The analogy coming from the people with kidney cancer where the removal of the primary in people who were suitable for the removal of the kidney primary. Two randomised trials seem to be doing better than when the primary sites are left in place and the seed verses the soil argument that leaving the primary intact may be releasing chemicals which potentially can facilitate seeds taking hold in the soil in other parts of the body. It hasn’t been shown in advanced cancers other than kidney cancer. This hypothesis which is now being tested in the STAMPEDE trial (ED: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) and is being canvassed in the clinics with patients newly diagnosed with metastatic prostate cancer. Person #1: I am just wondering what the role of radiotherapy is in advanced prostate cancer particularly where it is metastatic to the bone? Is it basically or is it a choice of either palliative type treatment or is there a treatment as per choice? Dr MacKean: That is a good question. When we give brachytherapy we have to give it properly because it doesn’t work if you give half the dose. Whether it is just localised or it is locally advanced or metastatic the tendency has been to use lower doses in men with metastatic disease than when you give it to them local. When you give it for curative disease from what we know you need to give at least 72 gray or its equivalent to get the local control up above 85% - 90%. So in my own practice I don’t make much of a discrimination I tend to give similar sorts of dose of 74, 76, 78 gray even for men with metastatic disease as men who have localised disease. The reason being you need that sort of dose to get the eradication of the cancer in the prostate primary and you can say to the gentlemen with a lot of confidence that we are giving these sorts of doses every day for men with localised prostate cancer and they seem to be getting through the treatment well. As long as you have 7 or 8 weeks where you can come along to the clinic we might as well do it properly and give the full protective dose even though it has gone outside of the prostate into the body. The aim is to deliver a dose which will stop the cancer from ever being a problem in the primary site down the track. Person #1: What I am particularly talking about here if you have a patient that has had his prostate removed so therefore the primary site has hopefully gone and you have bone metastases turning up around various places in your body, is there a role for radiotherapy there? Dr MacKean: That is a good question. When they do remove the prostate then local control within the pelvis is pretty much 90%. In terms of macroscopic recurrence, that is a nodule of cancer, coming back in where the prostate was removed. The risk of that happening after surgery is less than 10%. You would be less likely to recommend radiotherapy to reach in where the prostate was if there was cancer elsewhere in the body. If someone was unlucky enough to develop a bump or nodule of prostate cancer that was pushing into their bowel or bladder then yes that would be treated on its merit with radiotherapy to relieve symptoms. Thankfully that is uncommon after surgery. Person #24: Thank you very much for your presentation. I was diagnosed advanced metastatic, six months later I had a month of radiotherapy for pain management to my pelvis and my shoulder would you consider without knowing how much radiotherapy I was given. Would that have treated the primary source? Dr MacKean: You would have to ask your doctor about that. Three or four times a year I see somebody like you who have been diagnosed with metastatic prostate cancer and they have cancer spots in the bones of the pelvis, the sacrum or a hip or one of the other bones in the pelvis. What we need to do is put all of the x-rays up on the viewing box and actually just map out where the prostate is and where are the bone metastases. Some of the time one can incorporate treatment of the bone metastases at the same time as treating the prostate primary and other times if the cancer is higher up in the sacrum it would be too far away from the prostate to include in the radiotherapy field. What you could do is ask your oncologist to draw you a diagram of where your radiotherapy to your sacrum was and see how graphically close or far away that was through the prostate primary. You should also ask your oncologist or urologist to periodically examine the prostate from time to time to make sure that has shrunk down with the hormone to a normal size and it seems to be responding to the hormone therapy. That should be a part of the ongoing follow up. They are not going to do the radiotherapy to the primary site. If you follow the results of the trial five and half years from now there is still a 70% chance your prostate will be nice and small even without radiotherapy just with the hormone therapy alone. It is something you can feel reasonably okay about - that your prostate should stay small with just hormone therapy alone. There is this provocative trial evidence in men with locally advanced prostate cancer suggesting that if you add prostate primary radiotherapy you can improve that local control from 70% to 90% with modern radiotherapy. Person #24: Thanks for that. They did say at the time prior to commencement of the radiotherapy that my pelvis in fact was riddled with cancer and they said they had never seen a pelvis so badly damaged. They targeted two thirds of the pelvis and it also included four secondaries. Dr MacKean: That might be difficult to just from size point of view to incorporate the prostate into that sort of planning volume. That might have made your radiation oncologist quite hesitant to suggest adding prostate radiotherapy if they were treating such a large amount of your pelvic bone. Did the radiotherapy knock you around a fair bit? Were you quite badly knocked around the pelvic radiotherapy? Person #24: Yes, putting it mildly I was. I don’t think I can have any more radiotherapy for quite a few years. Dr MacKean: If they had tried to add the prostate treatments to those large pelvic fields it might have knocked you around a bit more and that might have been part of the thinking of your radio oncologist that it just would have been a bridge too far. Person #22: I had a radical 10 years ago and unfortunately my PSA did not drop. I have been on hormone treatment ever since with reasonable control. It is beginning to come up a bit now but it seems to be stabilised just at the moment. My theory was that probably I had an extension of the disease possibly into the lymph nodes or some other part of the body. When they had done CT scans and bone scans I have always been clean. I understand if you go into other parts of the body there are perhaps increased risks with radiotherapy. Are there new techniques MRI or PET scans to possibly identify working where the cancer may be in a preliminary situation like mine? Are there severe dangers in using radiotherapy in other parts of the body? Dr MacKean: So the first question. Are there new ways of imaging the body? I think the PET scan is still investigational in prostate cancer. There are two reasons for that. First of all PET scans involve an injection of the radio labelled glucose and only some cancers are actively take up or metabolise the glucose and thus show up clearly on PET scans. PET scans have been shown to be useful in restaging people with colorectal cancers, lung cancers and melanoma. In some other cancers such as prostate cancer which often metabolically is quite a low metabolic rate valve that may or may not take up glucose. So PET scans are a bit hit and miss in trying to work out whether people have a reoccurring of prostate cancer or not. I think bone scans and CT scans are pretty much all that we have relied on until the present and both of those are fairly crude. In order to show something on a bone scan it has to be at least 1-2cm in size and similarly with the CT scan it has to be pretty much 1cm or bigger to try and work out whether a lymph node is involved or not. The CT doesn’t tell you a lot about if the lymph node is enlarged for benign reasons or because it is enlarged because it has cancer in it. I think we again come back to the MRI scan as potentially the modality of imaging which is going to help most with restaging in particularly in the pelvis. The MRI scan can actually give a higher chance of detecting microscopic or small bone metastasis. MRI scans can detect bone metastasises less than 1cm in size. It may not be seen on a bone scan or a CT. An MRI scan also looks inside the architecture of a lymph node. So if you have an enlarged lymph node you can actually look at the fat content of the lymph node. Normal lymph nodes have a fatty consistency inside the centre of the lymph node and if there is cancer in the lymph node then you lose the fat content of the lymph node. It has a difference appearance on the MRI sequence. I think in the near future there will hopefully be more recognition about the essential role of the MRI scan staging people initially at the time of their diagnosis. I think that is being done much more commonly in the last year or two. If you are thinking about doing surgery people are now having an MRI scan as part of the initial management prior to surgery. Sometimes it is showing up something unexpected such as an involvement in the seminal vesicle, or extension through the capsule T3, or a lymph node which hadn’t been previously suspected on bone scan or CT scan. Often surgery can still safely proceed but the patient is better informed about what the surgeon is going to find. The surgeon has a better idea what it is all going to look like when you go in to have the removal of the prostate. You might go in prepared to take the lymph node at the time of the surgery or be prepared to go a bit wider on one side if it is starting to go outside the capsule on one side. The use of MRI scan is now fairly well established as part of the initial staging for men newly diagnosed with prostate cancer and being considered for surgery. I think what will happen in the next two to five years you will start to see MRI scans being used as a part of ongoing follow up of management. The main problem of course is the cost and lack of the Medicare rebate. The second part of your question is radiotherapy potentially dangerous when given to other parts of the body and the answer is yes. It is potentially dangerous. So when we use radiotherapy in other parts of the body doctors are quite conservative with the sort of doses that we use. If we are shining radiotherapy at the bone for example then we are using low to moderate doses of radiotherapy something in the order of 20 gray or 30 gray. Not very high doses and that is because of the potential adverse side effects of radiotherapy when you shine it at different parts of the body. So when you are going to use higher doses of radiotherapy (and I think you are going to be getting a talk from Dr Farshad Foroudi about stereotactic radiosurgery for bone metastases later this year) when you are using a very high dose, a single dose or a few very large doses then you want to minimise damage or keep the treatment safe then you have to use very very tight margins. Even then there is the potential because the doses are so much higher giving 20 gray in a single dose or 40 or 50 gray in five doses then because you are using such large doses you have to keep the beam away from the good parts of the body. That is a huge challenge in stereotactic radiosurgery. That is one of the reasons why it is only available at the moment in a small number of centres. It is something that each case has to be individually assessed for its safety because of the potential for damaging other tissue in the body. Person #22: You mentioned the cost but I guess from what you are saying surgery on things like lymph nodes if cancer is found there may be a possibility if not more permanent to radiation. Dr MacKean: So this has been a trend in the surgical community in recent years. So fifteen years ago in the late 1990’s was when they started to do what’s called nerve sparing radical prostatectomy, removing the prostate primary but trying to spare the nerves on either side. That was the first major advance in surgical technique and that was popularised by a surgeon called Dr Patrick Walsh from Memorial Sloan Kettering Cancer Center MSKCC. He taught a generation of American urologists how to do a nerve baring radical prostatectomy. That not only improved the chances that a man would regain full bladder control reducing the risk of incontinence by preserving the nerves but also offered the possibility in some, but not all, men a return of an erection of the penis after the surgery. Compared to when they didn’t do or were unable to do nerve sparing there really wasn’t very much in the way of erection function at all. That was the first biggest advance in surgery in the late 1990’s. Then I suppose the next advance was groups of surgeons looking at removing lymph nodes at the same time as the surgical primary. This is something that started in Japan. The Japanese have been doing this for quite some time and also in selected groups of people in the United States and Canada, either removing the lymph nodes as part of the open procedure or doing a separate procedure using laparoscope doing it laparoscopyly with keyhole surgery. There are quite a lot of studies now published looking at the role of lymphadenectomy as part of the surgical management of men with prostate cancer. In some selectively what the surgeon usual does is they decide before the operation based on the Gleason score, PSA and X-Ray radiology findings whether they are just going to remove the prostate or whether they are going to remove lymph nodes as part of the procedure. It does add time to the procedure it adds between three quarters of an hour and an hour and a half for the length of the anaesthetic. There is also a bit more in the way of post-operative pain and discomfort. There is a requirement of leaving drains in and there can be some issues with healing it can take a bit longer. The thought was maybe if they removed the lymph nodes surgically at the same time as the primary would that helping and improving the results. I went to a presentation at the Melbourne prostate conference last year where there was a very good review from one of the big American groups of this question and the answer is actually now being answered in the negative. So they looked at whether men who have an extended pelvic lymph node dissection as part of their radical prostatectomy when followed were doing better in the long run compared to men who just had the prostate primary removed. What they tried to do was they matched men with similar Gleason scores and PSA’s and T stages. There is no evidence that the pelvic lymph nodes dissection is actually a therapeutic procedure, it is more diagnostic information. It tells the pathologist whom is able to look at the lymph nodes under the microscope and see whether they are clear or they are involved. If the lymph nodes are clear that is a good problematic sign and if they are involved that may mean that the gentlemen is at a higher risk of something else happening down the track or relapses. The actual removal of the lymph node as part of the surgical procedure did not improve the long term survival of the men that had that procedure done. So since that information has come back, the enthusiasm for doing extended pelvic lymph node dissection as part of the operation has waned slightly. There was this burst of enthusiasm for using this particularly using the robotic surgery because lymph nodes can be removed robotically and people recover more quickly if the lymph nodes are removed as part of an open radical prostatectomy. The enthusiasm for thinking that this extended pelvic lymph node dissection is actually improving the cancer results hasn’t been shown to be the case. Chairman Bruce I must thank you and excuse myself. Jim will continue to control the meeting which may run until 11.30am. Person #35: You mentioned stereotactic radiosurgery before, what is your opinion on men with five or less very small metastases on being able to radiate those with high radiation and ‘cure’? Dr MacKean: I must admit I do not have a firm opinion about this. Like other people I am trying to find out as much about it as possible. I have attended meetings in Europe where enthusiastic presentations are being made about the use of stereotactic radiosurgery for people with low volume metastases. I think it is still an open question. There is interesting work being done from places like Boston, Florida, California and there is a very well respected group in Pisa, where the leaning tower is, in Italy. At the moment it is only being done in a small number of centres. Now it is offered in a couple of radiotherapy centres in Australia. At the Peter McCallum hospice in Melbourne, and I think you are going to hear a presentation from Dr Farshad Foroudi about that later in the year. It is also offered by a fellow called Dr Mathew Foote who is a young radiation oncologist at the PA Hospital in Brisbane. It may be available in other metropolitan hospitals as well. I don’t have an answer to your question. What I do if I see somebody like this and we ask the question then I do refer people to Dr Mathew Foote for an opinion, at the PA Hospital. He is quite happy to give an opinion. He has treated a number of people who have solitary, but that is a single bone metastases. He has decided not to treat people who have multiple bone metastases. It is so much an individual case by case thing and I wouldn’t like to prejudge the predictability for or otherwise for an individual person. I think it is still an open question to whether people are being materially helped or advantaged by treating the small volume metastases aggressively with radio surgery. One has to be worried about potential for harm. I am quite conservative and I admit I am not an expert in this area. We are lucky in Australia to have people like Dr Farshad Foroudi in Melbourne and Dr Mathew Foote in Brisbane who can look at the person and look at the scans and try and give a sensible opinion about it. Jim Marshall said Dr Farshad Foroudi will be talking with us in August. The maximum number of small metastases he will treat at the moment in his trial is 3. Are there any other urgent questions before the Dr MacKean has to go? Dr MacKean as you have heard is a doctor who can explain things very well and clearly. He said how he refers patients to other doctors for an opinion. Dr MacKean is happy to have patients referred to him at the Wesley. Jim Marshall thanks Dr James Mackean on everybody’s behalf for giving up his very valuable time. Person #20: Just a question for a friend who has been diagnosed with local prostate cancer and received low dose radiation seeds, he is still having to go to the toilet after 2 or 3 months every half hour. He is very concerned about that. Dr MacKean: That is not right. He should go back immediately to his doctor and get treatment for that. There must be something that can be done. If he was my patient I would ask him to come and see me as soon as possible. I am sure the urologist or the radiation oncologist who did the procedure would want to know about that. What he can have done is several things that might help. He could have a trial of anti-inflammatory medication, I use something like Voltaren it is a dose of 25 or 50mg twice a day. So there should be an explanation and a treatment for that because it is highly unusual and it suggests that he’s got lots of swelling in his prostate so we treat that with anti-inflammatory medication. Person #20: Thank You. Person #35: I had an MRI over 4 years ago before I had my radical and it cost $500.00. Dr MacKean: It still is about the same price it has some down a bit. Some places offer it for $350.00.Some places using the multi -parametric MRI might charge more than $500.00. Did it make any difference to your management or did it help your? Person #35: – Well no because it did not show anything outside the capsule and the cancer came back so I would say it didn’t help. Unfortunately that is just the luck of the draw. My first PSA result after the radical was less than 0.1. I had a radical in April and the first test was in June/July and the next one in September and it started to rise a little bit and continued to sky rocket after that. The MRI didn’t show it anywhere else. It obviously escaped from somewhere along the line. But life goes on. I am on continuous hormone therapy and it works fine. Person #35: - Donald Mackay My Gleason score is 9, 4+5. I have had radiation, but a year off all my medication, and my PSA has gone back up to 10 so I have gone back on hormone. Is the original Gleason score of 9 still relevant? Dr MacKean: Yes and no. Having had radiation therapy to your prostate, if we follow the results from these randomised trials, there is a 90% chance that you won’t have problems with it coming back or growing in your prostate. You have hopefully eradicated the seed which is basically you’ve now have a quiet, well behaved, prostate hopefully now and into the future. The Gleason score would have been used by your Doctors to determine how long you would have been offered the hormone therapy as part of your initial management. If you’re Gleason score had been 6 or 7 they may not have used any hormone therapy or used 6 months of the hormone therapy as a part of your initial management. Your Gleason score of 9 they might have talked to you about continuing the hormone therapy for 12 or 18 months as part of your initial management before you were able to go on a holiday from it. So is the Gleason score relevant now, not really in terms of where we go from here. People with Gleason scores of 9 respond just as well to hormone therapy just as well as people with a Gleason score of 6’s and 7’s. The Gleason score does not tell us anything about how in the future your cancer will remain sensitive to hormonal therapy. It doesn’t tell us about the future one way or the other. About 15% of people I see have Gleason scores of 9 or 10. We just don’t begin to understand why some people have lower grade and some people have higher grade presentations it is a complete mystery. We have got absolutely no idea about why is it that different people have different patterns of prostate cancer under the microscope at the time of presentation. It is one of the things that we do not begin to understand. Person #24: When I asked you about radiation to my pelvis and targeting the primary source you mentioned that perhaps once a man has had radiation that the prostate checked. Is that once every year or once every three years? Dr MacKean:: Once a year for the Doctor to examine the prostate. Person #31: I had brachytherapy and external beam four years ago. In the last couple of months I have had urgency in my bladder. Dr MacKean: You should probably be with the radiation oncologist. There is a condition called radiation cystitis. It is a late effect after radiation or brachytherapy. If the problem doesn’t settle quickly with an anti-inflammatory then we use a treatment called hyperbaric oxygen therapy. Where you go into the hyperbaric chamber and have a course of treatment and what that does is help the healing process because the thought is that in people with recurrent stinging, burning or frequency actually means they haven’t quite healed properly after the high dose radiation. If you are my patient you should come and see me, if you had it elsewhere you should find a friendly radiation oncologist or come and see me. Person #15: should you GP or Urologist perform the annual DRE after radiotherapy. Dr MacKean: Some GP’s are very good at this and others are hesitant. If your GP is quite confident about doing it then that would be fine. You just need somebody who knows what they are doing. Dr James Mackean Signs off and thanks for being invited to talk. Members thank Dr James Mackean. Warning! The transcript above was prepared from an unclear recording by someone with no medical knowledge whatever. Parts of it will certainly be wrong. Ask your doctor about anything that you read here. Person #15: What is the name of the radiation oncologist that will be addressing the August meeting? Person #15: Dr Farshad Faroudi. Peter MacCallum Cancer Centre. Person #20: Just an observation from what Dr James said it is important to keep cancer in the primary source then surgery where it is possible is the best option. Is that the conclusion you came to? Person #15: No. Radiation vs. surgery - for men with locally advanced, or more advanced the doctor has to look carefully at the details. Locally advanced and more advanced are mostly treated with radiation + hormone therapy, or just hormone therapy. When it was clear I was locally advanced my urologist sent me immediately over to radiation oncology. I sought a second opinion from another urologist, but he too said radiation was the best option. It is reported that some doctors are using surgery on selected patients, but for locally advanced and more advanced prostate cancer but it is common to use radiation with hormone therapy, or just hormone therapy. Person #20: Another friend of mine has really advanced cancer. I think his PSA is 390 and he is still going to an urologist, a very good urologist. One I think we all know. I would have thought he should have been going to a medical oncologist at this stage. What do you people think of that? Person #15: Our chairman, a retired radiation oncologist had a clear policy when he was in practice - as soon as it is out of the box a medical oncologist should be involved. A study which I sent to you in the last few days and going to send in the next few days, showed a study of the veterans in the United States. They have an enormous data base, all the people go through the one system. They found as soon as there was a medical oncologist involved the longer the men live. Obviously it depends on the quality of the doctor involved. Person #31: That is the thing finding an oncologist that really knows prostate cancer well. Person #39: I had a call this morning from a lady whose best friend has a PSA of 100. The PCFA Ambassadors should be hoeing away out there in the fields to make sure the message keeps getting out there that people are adequately tested. Like I said PSA of 100 and possibly metastatic and he is having scans today. Person #24: and Person #35 gave out 600 flyers about the PCFA Ambassadors at the Surat Basin Energy and Mining Expo at Toowoomba last week. Interesting a lot of men we spoke to felt that if they had had a colonoscopy and the results were all clear then the prostate was fine. We would then have to tell them no sir this is just not the case. We have a lot of work to do with re-education. Members sign off. These Minutes of the Teleconference are general in nature and not meant as advice. 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