Mike Wallace: Just to give you the setting of our MDT and how we work. We meet weekly; we discuss 30 to 40 patients per week. We cover the whole range of urological cancers, we discuss new cases, we discuss recurrent cases and management problems, we have between 20 and 30 people in our meeting, consisting of, as you see there, all disciplines, the complete spectrum from consultants down to medical students, we have two and a half hours to do it and we go at a pretty good pace and if I seem a bit curt in this presentation, that's because I am and because we have to get through these cases.
So let's have the first case:
Right this is a 69 year old man, went to his GP with symptoms of a urinary infection given antibiotics, GP did his PSA at the time of presentation when he had an infection, it was in the letter of referral so we sent him to our nurse specialist to have a PSA clinic to reassess. The Prostate was examined felt to be a little suspicious, the PSA was repeated it was coming down. Patient was bought back a gain, PSA checked again still coming down. Not happy yet; repeat further PSA, gone back up again, sent to our clinic for biopsy.
There is something relevant about his history that we need to know; 38 years ago he had radiotherapy for testicular cancer. He's had two heart attacks; he's had a minor stroke from which he has made a good recovery. He's still getting some angina.
Now let's have a look at the pathology.
Dr Flynn Chan: That's a cross section of the prostate, and the transition zone which is in green and blue and the site of TURP's. The part that is in yellow, the peripheral zone is where most cancers arise from and is targeted in Prostactic biopsies.
This shows normal prostate glands in stroma.
This is how the Gleason score is assigned, it is based on the overall appearance of the cancer, on the top is the low Gleason which is a well defined nodule of cancer, and at the bottom is poorly differentiated cancer, or the Gleason 5 in which you just see a few cells invading the stroma of the prostate.
This is the case that we were discussing today, this was a Gleason 3 plus 4, so Gleason 7 cancer.
Just to summarize this was present in a number of the biopsies with 45% of the cores of the right side positive and 70% on the left.
Mike Wallace: This patient came back to clinic was seen by a colleague had all the options discussed with him and opted for active surveillance. I thought; was that the right treatment course? We ought to discuss it. Alright so has this patient made the correct treatment choice: Nick?
Professor Nick James: Well one of the things we need to discuss obviously is whether we can offer him radiotherapy, there's a number of complicating factors here, one of them is he previously had radiotherapy before, of course for testicular cancer, now the likelihood is that it was so long ago that we wouldn't be able to find his radiotherapy treatment details, none the less we can make a reasonable estimate on what's likely to have been treated. And my feeling is that we could offer him radiotherapy in which case we'd offer him hormone therapy with it as well, the snag is that the drugs like zolodex carry the risk of exacerbating cardio vascular risk factors, he's got angina, he's had a stroke, he's had an MI, so there is significant risks attached to giving him hormone therapy. It's a bit border line as to whether you could give him radiotherapy, but it is certainly an option.
The second question of course is you've got to monitor it and continue monitoring is how we do it?
So one question I'd like to put to you Peter is; should we do further imaging? We haven't done any staging tests apart from theTRUS biopsy.
Dr Peter Guest: No we haven't done any imaging at this point at all. His PSA is relatively low so he should be at relatively low risk of metastasis on that basis, but he is a T2 and he does have Gleason 7, so our options are: first of all staging for the local disease: MRI, and staging for the distant metastases: MRI and bone scan.
What's the right thing to do? I think you should probably stage him to get an idea of what is going on at this stage to help plan for further management.
Mike Wallace: Ok so our conclusions from this. We won't overturn his treatment decision but we've got to follow him with greater vigilance because in this case the PSA may not be a very good marker. We ought to get some staging done for his next visit and we ought to make sure its documented that he ought to be followed with much greater vigilance because the rectal exam and his PSA may not tell us when we need to intervene and change the treatment.
Professor Nick James: And if there's a question of whether we should do further biopsies or not, I mean what would you feel about further biopsies?
Dr Flynn Chan: I think if you are actively monitoring him with Gleason 7 and he already has significant chance of having adverse pathological findings with the possibility of extra prostatic extensions, a biopsy at this stage would not help. Possibly if his PSA is rising in the future.
Mike Wallace: Let's go onto the next one. This is another case that presented two years ago with a urine infection, chronic retention had some bleeding, and a PSA of 64.
On antibiotics his PSA came down, he had a resection of his prostate, a big resection 57 g, it was all looked at, it was all benign, with some inflammation, his PSA afterwards had started falling, we were reasonably happy.
His PSA didn't go on falling as expected, he was reassured about it, he was well, there was nothing to feel in his prostate but is PSA didn't go on falling. And earlier this year we started getting worried about this PSA, and he was then referred to us for prostatic biopsies, at which time the left lobe of his prostate was just a little bit suspicious.
Dr Flynn Chan(20 mins): Just to say that the transition zone is the site for hyperplasia and that was sampled in the TURP but the cancer is from the peripheral zone. Next slide
This is the TURP which he had initially ,it was the tissue of benign prostatic hypoplasia.
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There were also some glands with pus in the view. So there was prostatitis
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These are the biopsies, and as you can see the cores look a bit blue and they are almost entirely replaced by the cancer, so that was Gleason 4 + 4 that is Gleason 8.
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That is just to highlight what the cancer looks like and that the glands which make up the prostate stroma are fused ,.
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Just to summarise the initial findings were benign, but the prostate biopsy showed that the left side cancer was Gleeson 4+ 4 , that's 8 and that, it was then in all 6 cores, with 90% of the cores involved and it also involved the nerves but on the right side there was no cancer
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Dr Peter Guest: We did some staging examinations on this patient; this is a bone scan that we do to look for metastatic disease. It's quite a good test, it's very sensitive, and it also picks up things which aren't metastatic disease, and I think we can see that picture of his head and neck on the top right of the screen there is some increased activity on the right of his neck. We weren't sure if that was metastatic or not so we had to have a supplementary examination to x-ray his neck.
The x-ray of his neck simply confirmed that he had old age and a degenerative spine, so he doesn't have metastatic disease according to his bone scan. We did an MRI scan of his prostate, now some people are a lot more enthusiastic about Prostate MRI tests than others, but it is a good test for, looking for distant disease. I am just going to stand up and show you some things on the screen, so I will shout.
This is his right kidney, this is his left kidney that's the aorta. We are looking for his lymph nodes as a sign of metastatic disease.
Again we are looking for lymph nodes in front of the Soas muscle and in front of the spine. And lymph nodes in the pelvis, at this stage it is not a lymph node disease as far as we can tell.
Now a bit of anatomy; this big white area is the bladder, this is the rectum and these are the seminal vesicles. The seminal vesicles are nice and white which shows that they haven't got a tumour in them.
He's had a TUR, where he's had a core of prostate removed from the central zone which it doesn't often contain cancer; that white bits where its been cored out.
We can see peripherally around the gland, this area is dark, that's the tumour, at what stage is that tumour? that's the difficult bit. One of the signs of an advanced tumour locally is a bulge or obvious tumour extending beyond the capsule of the gland. Now in this case we did feel the capsule was bulging and diagnosed it as a T3 tumour, without any lymph nodes and without bone metastases.
Mike Wallace: The reason for bringing him to this meeting was because of the time he took to go through these sequential investigations. It took three months so we cocked up here, why did it happen? Richard what did we do wrong and what can be done about it?
Richard Gledhill: The thing that went wrong was that this patient was seen in clinic by one of the junior doctors who essentially did everything right apart from getting me involved. Because one of my jobs is actually to expedite these sorts of cases so that we don't get investigations that are just left lost in the post. So I go and hand deliver them, I put forward a good case to the technicians who are doing the investigations and making sure that our patients get appropriate and timely and investigations and we don't have a 3 or 4 month gap.
Mike Wallace: Ok Nick, what do we do now?
Professor Nick James: So to summarise the case we've got a patient with a T3 tumour that's to say its gone through the capsule of the prostate gland, there's no evidence of lymph nodes spread, he's got a rather high PSA, and he's got a high Gleason score a Gleason score of 8. So although he's got no evidence of spread, this is a cancer that is at very high risk of spreading, and we would not want to offer him surveillance and monitoring for example. We've got to treat him. Now my feeling is with cases like this the best treatment is a combination of hormone therapy and radiotherapy that we have offered him. And so we have started him on the goserelin injections every four weeks,he will have radiotherapy for 4 weeks and have adjuvant hormone therapy, that will run for a total of three years from start to finish.
Richard Gledhill: He was seen in the clinic he was counselled he was given the options of whether he wanted this treatment or not, and supported through the relevant information so that he could make a decision choice and know what he was likely to expect.
Mike Wallace: What I failed to say is that after the meeting you immediately phoned him up and got him up to speed.
Richard Gledhill: Absolutely. He started his treatment seven days after our meeting, so we expedited our treatment plan.
Mike Wallace: Third case, it's slightly unconventional. He was having a great deal of PSA monitoring 2000, 2002, very comfortable with that PSA level. Then all of a sudden it jumps without any significant symptoms. Clinically he had a T3 cancer; he had biopsies and 7 out of the 8 biopsies showed Gleason 10 cancer. The bone scan is negative his MRI scan shows no metastatic regimes. He comes to us, I felt his prostate and I thought is that cancer going into rectum? He was seen by Nick and we discussed what should we do about his treatments.
Professor Nick James: This is obviously a very unusual case because the rate of rise in the PSA was quite dramatic, so between the biopsies that we'd seen and a few weeks later looking at the PSA, it had jumped by about 25%. The PSA was going up at a very alarming rate.
The other thing that was unusual about the case (relatively that is but not necessarily to this audience) was that the patient himself had very clear ideas about what he wanted to do. He was very clear he had a very nasty cancer, he wanted chemotherapy, hormone therapy, he wanted the works and the kitchen sink thrown at this thing. Which we were very happy to agree with, because I felt and the patient himself felt that hormone therapy alone was not going to be a good option. If you.treat a tumour like this with conventional treatment like hormone therapy the prognosis is not good.
So what we did was we started him on a combination of goserelin together with docetaxol which is a treatment licensed for use in metastatic disease. As you can see the PSA fell, but not as much as we might have liked, it hit a 6 at the point at which he had completed all hormone therapy and they planned to give him radiotherapy, then he went for a radical prostatectomy and you can see that the PSA fell still further.
But we will review the pathology from the prostatectomy now.
Dr Chan: (27 mins on tape counter): That's the prostatectomy specimen, which shows the Gleason 5 +4 that's Gleason 9 cancer, it did show effects of his treatment.
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The dark blue is the cancer cells and the clear colour areas which you see are the fat which surrounds the prostate . Now there was cancer extending into the fat, surrounding the prostate so there is prostatic extension.
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The pink, is smooth muscle, which represent the rectal wall, and there was invasion of the rectal wall with the tumour.
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What you can see is that there is some red ink at the edge of that picture, and that is the surgical margin, and this was also positive, , so the tumour had actually reached the surgical margin .
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So to summarise this was a 5cc Gleason 9 cancer with extensive extra- prostatic spread, both seminal vesicles were involved with positive margins, and the rectal walls were also involved with tumour. There were lymph nodes that were removed and these were tumour free so he didn't have any cancer spread through the lymph nodes.
Mike Wallace: So he had a pretty stormy time post operatively, and because of the rectal involvement, this was done through a conventional open procedure.,.
Richard you looked after him when he went through this, and now is the time to decide what is the next step in treatment. Does he go on to radiotherapy?
Richard Gledhill: Well quite clearly to have two radical treatments, surgery and radiotherapy, you have to be fit. This gentleman was a former Olympian so he was certainly quite fit. However you need to make sure that after the initial treatment the plan doesn't change due to people not being able to tolerate the treatment, so active involvement with this chap, we are able to re-assess and then to consider further treatment to offer.
Professor Nick James: The treatment we had originally planned was to treat with radiotherapy, now the concern is if you give radiotherapy to an operated area then you've got a much higher risk of complications, and in this case the tumour was involved in the rectal wall, so we had to resect part of the rectal wall and the resection area would be included in our areas to be treated with radiotherapy, obviously deliberately as that is where part of the tumour was left. So essentially this was a very difficult decision and in the end we decided that we should opt for post operative radio therapy. Simply because immediately post surgery the PSA level was 1.1 so we were still highly suspicious that there was significant tumour still there. And after allowing for a bit of post operative recovery we went ahead with this and it was tolerated. So you can see the PSA has fallen further and hormone therapy involved here as well and it has remained low so we're currently pursuing adjuvant therapy with hormones .
Mike Wallace: The final case, this man is 54 fit and completely a-symptomatic, goes for a routine medical prior to an overseas posting, and clinically has a T3 cancer and a PSA of 45. Straight away we get him up for biopsies which show a Gleeson 4+5 cancer, and we got on with his images straight away which shows no metastases and put him on bicalutamide and sent him to Nick James.
Dr Chan: So that is a Gleeson 4+5 cancer.
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Actually in this case the biopsy confirmed that it was a T3. You can see there are blue areas which are cancer going into the fat, so it was outside the prostate so this was confirmed from histology .
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So that is just to show you the biopsy, it was 9 on the right side and on the left side 4+4 which is 8 and that was just in one core, there was extra prostatic extension and nerves were also involved..
Professor Nick James: This obviously again is a difficult management problem. It is a young man, and the controversy is whether you should offer radiotherapy plus hormonal therapy or just radiotherapy .. Conventional wisdom says that with a tumour that is likely to have spread that you should just offer hormone therapy, and then there is a debate to be had if you should just offer Zoladex, which wipes out the androgen functioning completely or just Casodex which blocks the androgens from getting to the cancer. Our opinion is that for men who are young and fit and also sexual activity ,is something they are potentially still interested in,, is that we should offer them Casodex rather than Zoladex, , because that preserves energy levels and potency rather better than Zoladex does or drugs like Zoladex. This is what we did we offered this in combination with radiotherapy. I guess we could be criticised as not necessarily being by the book management, but we felt that this was the right management for the patient. That is what we did. We went ahead with hormone therapy and radiotherapy.
We offered him radiotherapy and subsequently we ended up stopping the bicalutamide essentially because the patient was experiencing some significant adverse reactions to it. Partly because he had a previously undiagnosed clinical insignificant liver condition that was being exacerbated by the bicalutamide.
As you can see as soon as we stopped it the PSA rose, which it does tend to because bicalutamide and drugs like it blocks the PSA production by normal prostates, there will be some residuals of normal prostate present in radiotherapy. But you can then see that the PSA has risen rather more slowly after the initial rise which was just the of affect of stopping the bicalutamide. Because the PSA was continuing to rise we did an MRI scan, conventional MRI scan and that didn't show any evidence of disease that we could image. At this point , this patient had been having a number of discussions with Richard about what else he could do, he was very alarmed about the persistent rise in PSA and also the lack of evidence as to where this was coming from.
Richard Gledhill: With this patient we did meet regularly because we have got this rising PSA, we've had radical treatment it limits what we can do, next to someone who's young. Essentially this patient wanted to have as much information as he could about what his options were. So I acted as an information bringer, and sign post so he could go and research potential future treatments, which he did.
Professor Nick James: And one of the things he came up with was; the debate we had been having was should we offer him a radical prostatectomy, up front we decided it was not an option because there was extra prostatic spread, but we do offer salvageable prostatectomy to radiotherapy failure, and what we found is biopsy the prostate of people like this, with rising PSA only 1 in 3 turned out to have cancer in their prostate, the other 2 in 3 the biopsy's are negative and the imaging is negative, so we don't know where the cancer is , which actually makes it very difficult treatment decision as to what on earth do you do next?
Clearly one of the culprits as to where the disease might be is the lymph nodes, but the problem is the imaging that we will see will tell you about the size and the shape but it won't tell you about the composition of things.
He came a cross a recently published paper from Holland , so he decided he would go and have his imaging done himself.
So let's go onto the next slide, I will hand over to Peter who will run through the imaging.
Peter Guest: It's a shame I wasn't able to offer this imaging. Nick as you know the limitation of imaging, we have this every week in the MDM's, whether a lymphnode is involved or not, and all we can really offer is how big is the node, the bigger it is the more likely it is to be involved. I am going to show you this node.
That node measure 8mm, I can't tell you whether that node is involved or not. The patient went on the internet and discovered this very nice paper that had been written by Professor Beranz in the Netherlands ,published in the New England Journal of Medicine 2 years ago. , I have been to some very interesting talks by this chap, about tremendously good results using a new form of contrast agents.
If I just remind you, the lymph node is naturally full of lymph cells and the function of lymph cells is to scavenge all the rubbish that goes through out systems, and one of the things it scavenges, if you inject ion oxide particles it scavenges those ion oxide particles out of blood. What that does in MRI' s it reduces the signalling of the lymph nodes. So normal a lymph node using this technique will go black, but a lymph node that contains a tumour, the tumour is going to displace those normal lymph cells and the lymph node will not go black.
Now I think on these slides; the abnormal lymph node is this lymph node here which has remained white but there is a little bit of black around it, because that is the little bit of normal lymph node around the outside. Up here is the normal lymph node. So what Professor Berentz was able to tell us is that that one lymph node in the entire patient's pelvis contained tumour and if you have a look at the next slide, this is Professor Berentz's final report and he drew a picture to show where the involved lymph node is, so a very interesting new technique.
Professor Nick James: But the problem is it doesn't tell us how we should manage the patient. So we have identified there a positive source for the PSA rise and the local cancer, but it doesn't tell us what we should do? So it comes back to the dilemma that Malcolm spoke of earlier; how do you treat lymph node positive disease?
At the time we gave him radiotherapy the paper that he mentioned hadn't been published so we did not treat the pelvic lymph nodes, even if we had this lymph node probably wouldn't have been in the field or would have been right on the edge of it. So we had various options we could do prostate biopsies to see whether there was disease in the prostate and then remove it together with the lymph node or just remove the lymph node on its own, or we could adopt some form of monitoring. We really couldn't make up our minds, so what I would like to do I would like to invite the patient himself to come and join us and stage, and we will have a discussion on what we should be doing.
Mike Wallace: I think you asked me, would I operate? And I said well I might, but I couldn't make a decision. It's not my decision really, there is no real good evidence on how to manage this case, so I said you have got to talk to the patient.
Professor Nick James: So Stephen, as you know, we presented you with a lot of uncertainty here. Would you like to tell us how you felt about the various options we were offering you?
Stephen Barton: Two key words for me in this whole process would be knowledge and control. Going to Holland for my MRI and actually seeing those images myself for the first time, seeing the images of the cancer inside me, gave me a picture, it enabled me to feel - although I am not part of the MDT, I am not there - it enabled me to feel much more part of the decision making process then I ever felt at any stage before. I have been checking with my wife recently about the early decisions that were made and referred to Zoladex or Casodex which should it be. I couldn't remember any of those discussions taking place, my wife reassured me that it did. I could not remember it at all because of the shock of the initial diagnosis.
Professor Nick James: You said that on the phone to me the other night and I went and checked and I documented in the notes that I had discussed it.
Stephen Barton: The precise question that he put to me is quite difficult to handle immediately; Strangely for hearing what was bad news from this MRI in Holland, I actually feel better, because I do know now what the problem is and where it is, I have been offered now the possibility of a salvage prostatectomy, and I was very wary about any body putting their knives anywhere near or inside my body, unless I was absolutely sure there wasn't cancer else where, and knowing that there is cancer else where means that I've got good reason to say, no I don't think I will take this slim chance that Mike Wallace has offered.
About not being actively part of this meeting, you were asking me earlier Nick if I could reflect on that. I already know three members of this team, although I had not met the radiologist or pathologist before. I have met the others in consultation and Richard quite often in clinic, and so there is a high level of trust being built up and I trust these people, so there is a high level of trust here. What I needed in relation to an MDT taking place after this new investigation had taken place in Holland, what I needed was to know when the MDT was going to take place and to know when I would get the results from that MDT. It didn't necessary have to be on the day, although Nick did very kindly offer to phone me actually on the day, although that wouldn't be possible with all 40 patients seen in the course of the morning, I realise that. But to know when I am going to have that information, and then the other thing that I have asked for from my consultants and Richard has been very helpful in getting this from people; has been written information because what I heard in consultation 2 and half years ago I just did not remember, so when I reviewed my own case earlier this year when my PSA was rising, I asked Richard to get all my notes for me he photocopied the whole lot and we read through them, and now I ask for a copy of every result, of every letter written to a GP of letters between the consultants. I think I shouldn't have to ask for it, I think that should be automatic and patients shouldn't have to ask for it and they should be able to opt out from it if they don't want that much information. But it has been a real help to have all that.
How I feel now; I am on no treatment and haven't been on treatment for nearly two years now, because the Casodex wasn't doing any good, I am content to watch and wait, knowing that the monitoring of this is very active, knowing that there are other weapons in the armoury that we can turn to, and also I am still completely fit, I am experimenting with changes to diet and if anybody wants to become a part of this MDT, this is potentially the largest consultation I have ever had! any answers on postcards over lunch will be very welcome, as to what you'd do next.
Professor Nick James: What we had hoped to do but we have run out of time, was to take questions as well, but I suppose it is over to you as to whether you would like to go and have your lunch or stay for some questions. What is the general feeling?
Vivienne Parry: I think I am going to stop you there and say if anybody has questions to come and ask these questions now, because now we have to break for lunch or we will run out of time all together with the programme.