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BRITISH BROADCASTING CORPORATION
RADIO SCIENCE UNIT
CASE NOTES Programme no. 8 - Prostate Cancer
RADIO 4
TUESDAY 20TH MAY 2008 2100-2130
PRESENTER: MARK PORTER
CONTRIBUTORS: ROGER KIRBY
PETER ALBERTSEN
PHIL KISSI
DAVID NEAL
PRODUCER: PAULA MCGRATH
NOT CHECKED AS BROADCAST
CLIP
Initially I saw a hospital programme back in October 2005 that made me aware that ooh what is prostate cancer, I need to get myself checked out because if these are the statistics that has been found then I could be one of those people.
PORTER
One of the 35,000 men who develop cancer of the prostate every year in the UK - meaning it affects nearly as many men as breast cancer does women, yet there is vast difference in public awareness. Most men don't even know where their prostate gland is.
Professor Roger Kirby is Clinical Director of the Prostate Centre in London.
KIRBY
The prostate gland is a chestnut sized gland that sits at the base of the bladder, so every time you pass urine you pass urine right through the middle of the prostate. And throughout life it progressively enlarges, especially after the age of 40, so that enlargement of the prostate compresses the urethra, reduces the flow and makes it a little more difficult to pass urine. It's also very susceptible to the most common cancer in men, namely prostate cancer.
PORTER
While prostate cancer can cause symptoms due to generalised swelling of the gland - such as needing to get up frequently in the night for a pee, or noticing that your stream isn't as powerful as it used to be - it has to be fairly advanced to get to that stage. Most men with these symptoms will have benign age related swelling of the gland, and a blood test is often only the clue in those with cancer..
KIRBY
PSA - or prostate specific antigen - is a protein secreted by the prostate and its function is to liquefy semen after ejaculation, turning it from a coagulum into a liquid fluid, it releases sperm allowing them to swim through the female genital tract. So that its function in sperm but it does bet absorbed into the bloodstream and it appears in about a millionth of the quantity in the bloodstream compared with in the semen. If the prostate's disturbed in any way, either by a benign enlargement or especially by a prostate cancer, then more PSA leaks out of the prostate into the bloodstream and the PSA levels rise. So it's quite a useful indicator of whether somebody may or may not have prostate cancer but it's not absolutely specific.
PORTER
It's an area that's attracted some controversy, and the bottom line appears to be, and my take on it as a GP, is that it's a useful tool but it's a relatively blunt tool.
KIRBY
Yeah some people call it PSA, they say it stands as a promoter of stress and anxiety, especially for GPs, other people, like me, who are keen on it say it's a providentially sent antigen. But it is controversial because it's not specific for cancer, it goes up in other conditions that disturb the prostate - prostatitis, biopsy of the prostate or benign enlargement of the prostate. And so there is a lot of overlap between other prostate conditions and cancer. But if you use the test skilfully and you maybe use some of the newer tests, that we'll talk about later, in the programme then it can be very valuable.
PORTER
And skilful use of PSA would involve what?
KIRBY
Well a one off PSA in somebody your age, for example, is going to give you limited information but if you measure it sequentially, every six months, every year, then you get a - what they call - a PSA slope or a rate of rise of PSA. And if the PSA is ticking along within the normal range and suddenly blips upwards then that's a warning sign that there may be something going on in the prostate.
PORTER
So which men are most likely to develop prostate cancer?
KIRBY
Well the most important factor is a family history and I had a patient in here today whose father had prostate cancer, his grandfather had prostate cancer and died of it and now his brother's got prostate cancer. So rather like breast cancer it can run in families. It's also more common in Afro Caribbean men, we don't quite know why, there's probably some genetic difference, we see it in Jamaica, in Africa and especially in North America. And there are also dietary factors - I think there's a link between central obesity and prostate cancer, higher fat intake and prostate cancer. So it's a sort of Western disease which is affecting more and more men as they age.
PORTER
But abnormal PSA readings only flag up potential trouble. The next step is to confirm what is actually going on, and that means your doctor will want to feel your prostate gland by inserting their finger into your rectum.
KIRBY
You can feel the prostate gland like a chestnut sitting at the base of the bladder, you can feel the back of it, which is exactly where the cancers tend to develop. So that's painless, I mean men are a little embarrassed about it and men tend to make more fuss about these things than ladies do of course but they tolerate that very well. And if you can feel a nodule or you're worried that the PSA is rising over time or is it above the normal level, which is 4.0, then you'd organised what we call a trans-rectal ultrasound guided biopsy, which is an ultrasound probe, about the size of two fingers, placed in the rectum, you can see the prostate beautifully as an ultrasound image - sonar image - and you put a needle, under local anaesthetic, with antibiotic cover, into the prostate and take usually 12 tiny slivers of the prostate, so called prostate biopsies and send them off to the laboratory.
PORTER
And that's the test that'll tell you whether the patient definitely has cancer?
KIRBY
Yeah, more or less, that's a much more definitive test because a raised PSA raises the suspicion of cancer, means that that patient's at higher risk of cancer than normal but it doesn't tell you whether they do or don't. Take a biopsy and then you know if there is or is not cancer there. But the only rider of that is that of course the biopsies are only samples of the prostate so you might have a small cancer that you miss but if you take 12 biopsies you pick up significant cancers.
PORTER
A recent study published in the Lancet found that the death rate from prostate cancer is much lower in the States, and continuing to fall faster than it is here. So why the growing difference? Professor Peter Albertsen is Chief of the Urology Division at the University of Connecticut and one of the study's authors.
ALBERTSEN
There are a number of factors that could be contributing. One of them could be the fact that we've been doing a fair amount of screening and treatment for prostate cancer in the US and those who are proponents of PSA testing focus on that as the probable explanation. Another possible explanation is in the last decade we've had a very aggressive programme in treatment of heart disease and as a consequence more men are living to older ages but also many Americans are now on a class of drugs called statins, which are designed to lower the cholesterol, there is some evidence to show that those statins might also be anti-cancerous and may in fact be impacting on mortality rate. Furthermore we tend to use surgery more often than you do in the UK, in the past the primary treatment for prostate cancer has been heavily radiation, possibly the surgical techniques could be better than the radiation techniques.
PORTER
What sort of uptake do you have for PSA testing in the States, is it something that's become almost routine for middle aged men?
ALBERTSEN
I'd say certainly in middle class and upper classes getting an annual PSA test is pretty frequent, whether it's reached a 100% I doubt but I think it's easily as high as 70 or 80%. And as a urologist I virtually never see a patient who's never had a PSA test before, most of these tests are given by the primary care physician and by the time I see someone frequently they've had 8, 9, 10 PSAs over the last decade and it's that one that's popped over four or some baseline value that concerns the internist that sends the patient in.
PORTER
Yes, I mean here in the UK you could almost reverse that and say it's unlikely to meet anyone who's ever had regular annual tests.
ALBERTSEN
I find it fascinating when I travel to the UK and talk to the physicians there the cultures in North America and in Europe - it's not just the UK but I think especially in the UK - is so completely different between the two societies.
PORTER
We're all party to the same data so it is the healthcare professional's interpretation of that data or is the difference in public opinion that might explain the gulf between the two practices?
ALBERTSEN
Well I think one of the major differences is our healthcare systems. In the UK you fundamentally have a government run system and that can be both a good thing and maybe not a good thing. In the US we're much more of the wild west where we are very entrepreneurial and we like to do things. And remember healthcare in the US is fundamentally a private system and therefore patients who want things can get them. What happens is it stimulates an aggressive use of all types of care, whether it helps people or whether it might not help people and that's where the controversy comes in. PSA testing, the idea of identifying a cancer early, is a very, very seductive hypothesis and when you immediately explain that to someone if you could get a blood test and you could find your cancer earlier how could that possibly be bad? And the answer is it can be bad if in fact you're not impacting the ultimate outcome of the disease and that's where the controversy lies. Just because we find prostate cancer earlier does not mean that we are finding the men who are destined to die from this disease. And I think in the US we're beginning to recognise that we are grossly over diagnosing this disease, in other words submitting many more men to surgery and radiation in the US than in the UK who are getting interventions which may or may not help them at all. The problem is it might help some of the men and that might be the explanation for the greater decrease in the mortality curves. If prostate cancer mortality is impacted by screening and treatment it then leads to the next question of how many men do you need to treat to save one life? And the estimates are going anywhere from as low as - you need to treat 20 men, to possibly as high as 100 men need to be treated to alter the outcome in one person. Then you get into the ethical or philosophical dilemma is if it can help someone at the price of possibly hurting 99 other men is it the right thing to do? And that's the pathway we might be heading down in the concept of screening and treatment for prostate cancer and why it's so controversial and why it's so important that the UK is running the very large protect trial that is being conducted there currently.
PORTER
Can you see a day when we might have a more accurate tool for determining a. which men have cancer of the prostate and b. which of those cancers are going on to be life threatening for the individual?
ALBERTSEN
You ask the absolutely most important scientific question being faced by researchers in the field of prostate cancer. We are still using the Gleeson scoring system, which was developed by Dr Donald Gleeson in the '60s, which is a low power view of the biopsy specimen. Despite its almost antiquated feel it is still the most powerful tool in protecting the long term outcome of whether a man has an indolent prostate cancer or one that will kill him. There's an enormous amount of effort being expended to look at the genomics and protonomic tools in various laboratories to try to come up with the genetic signature that will dictate whether you have a bad prostate cancer and a good one. So I'm hoping in the future we will come up with that test because it will certainly spare many men needless surgery or needless radiation and would also help men who have been hesitant to get a PSA test or some other way of finding this disease earlier, if in fact surgery or radiation makes a difference.
PORTER
Professor Peter Albertsen talking to me earlier.
Treating cancer of the prostate is almost as controversial as screening for the disease. Most men will be offered one of three options - no actual treatment but active surveillance, radiotherapy or surgery - and there is still hot debate as to what works best for which men. Professor Roger Kirby.
KIRBY
I've just been seeing a patient this afternoon actually who is exactly in that situation - a PSA of seven, biopsies - three of the biopsies out of the 12 came back showing prostate cancer. So we've been talking with him about the treatment options. Number one treatment option is what we call active surveillance where we don't do anything but we just measure the PSA over time to see if the cancer is one of the more aggressive types that is growing or whether it's the low aggressive type and therefore can be safely watched.
PORTER
And the rationale is that it's more likely to be slow growing?
KIRBY
Well the biopsies give you a pretty good indication of that actually, so in his case it was a low grade - a Gleeson grade six - you can score from six, seven, eight, nine and 10 and the 10 are very aggressive, the six are on the low aggressive side. So in that patient's case it was a Gleeson six, three of the biopsies were positive, so that means there's probably quite a bit of cancer there, is only 57, so he's a youngish patient, so that would make us lean more in the direction of advising something more active than just watching and waiting. But you know we take patient preferences into account.
PORTER
But you might have somebody equally who was in their 70s who had a relatively slow growing tumour that you might not want to touch because it might never ever cause him any harm?
KIRBY
Absolutely, especially if only one biopsy's positive and maybe only a tiny proportion of that biopsy, that would be exactly the type of patient that you'd watch and wait. And there is now quite a pronounced move for what we call active surveillance rather than watching and waiting in these low risk patients.
PORTER
So let's assume the patient in front of you is the sort of patient that you'd like to intervene in some way, requires treatment, has either got an aggressive cancer, is young or whatever. You're a surgeon, does that mean you always go for surgery?
KIRBY
No I think more and more we think that the patient choice is paramount in this, particularly in this disease which is still very controversial. So we lay out all the treatment options in the same way as we go into Sainsbury's and you see all the food available there - people choose and they choose what car they're going to drive don't they. So you say to them well listen we can remove the prostate, which removes the cancer, of course it has some side effects - these are minimised by new technologies but still important. We can leave the prostate in place and try and eradicate the cancer with the prostate in place by radiotherapy - either external beam radiotherapy over a six or seven week period or so-called Breaky therapy, Breaky means short wave therapy where radioactive seeds are implanted into the gland and they eradiate the prostate from the inside out and that reduces some of the side effects but there again it causes some others. Or in patients who are not really suitable either for surgery or for radiotherapy there's hormone therapy, there's even trans-rectal high FU or high intensity focused ultrasound which actually sort of cooks the prostate cancer inside you and you can even freeze the prostate as well using cryo-surgery. So you have a lot of treatment options and patients are sometimes baffled by this array, as you can imagine.
PORTER
Phil Kissi found out that he had cancer of the prostate in 2006 when he asked his GP for a PSA blood test after watching a TV programme on the subject. He chose to have surgery using the latest robotically assisted keyhole technique - the Da Vinci prostatectomy - because he hoped it would mean fewer long term side effects like incontinence and difficult getting a proper erection.
KISSI
Initially I saw a hospital programme back in October 2005 that made me aware that ooh what is prostate cancer, I need to get myself checked out because if these are the statistics that has been found then I could be one of those people in that category. So I just went for a normal check up with my doctor.
PORTER
But you had no symptoms at the time?
KISSI
None at all.
PORTER
So you had the PSA blood test?
KISSI
I had the PSA blood test and it was an average reading. And I went back two months later because I still remembered watching this TV programme while I was on leave. And to my surprise it was slightly high but because I was a keep fit fanatic my doctor thought maybe I'd been overdoing it in training. And my doctor was really good, really good, he said okay not a problem, gave me a check up and it was slightly high and he said, you know what I'll refer you to the hospital just to put your mind at ease.
PORTER
So there'd been a gradual increase in ...
KISSI
A gradual increase.
PORTER
It was eventually confirmed that you had cancer of the prostate and you're a young man - how old are you now?
KISSI
I'm now 50.
PORTER
So you're sitting there, you've been told that you've got cancer - that must have been a shock?
KISSI
It was a shock but then again I'd done my research around the prostate cancer website and other websites but mainly I was kind of like half prepared for it. I was given a counsellor that went through - and also the consultant - that talked me through the various types of treatment. And I had no doubt in my mind the one that stood out was the Da Vinci robotic treatment, which I felt was better for me which was nerve sparing.
PORTER
And what about it, you say it's nerve sparing, I mean presumably you're worried about the side effects of loss of sexual ....
KISSI
Yeah I mean - I mean as a young man you do worry about that side, that ooh maybe if I have this operation I might not be a "man" in commas and I wanted to be sure that I was looking at the best possible offer out there. And I conveyed that view back to my counsellor and to the consultant.
PORTER
And what about side effects, I mean with - continence can be a problem, incontinence, did you have any leaking to start with?
KISSI
Oh yeah definitely, I mean initially I was using about 10 pads a day. Now basically I use one pad, if I'm doing aggressive exercise - running or rushing for a bus I might have a little trickle. So it's just there as a safety net.
PORTER
Did you discuss your concerns about your ability to get an erection with your partner?
KISSI
I showed her some information pack I had already from prostate cancer and I said look I could have problems here. And the first thing she said well the most important thing is your life, if you can survive this I'm more than happy, let's just take one step at a time. And that helped me a great deal because my partner's young, she's only 34, 35, you know let's be honest about it, being a man you think oh if I can't do the bedroom function maybe she'll leave me, you know, let's not mix our words about this, people do get that sort of feeling and you do need that support from your partner to say look I will stand by you through thick and rain. And then we went through the various treatments and it was vital that she understood what emotions I was going through as an individual as well.
PORTER
And since then you've had to use some help with - medication to get some erections albeit hopefully temporarily?
KISSI
Yeah.
PORTER
Has that been an issue for the pair of you?
KISSI
No, no in fact it's quite funny really because she says to me - oh this one is much better than the other one. So we mark the degrees of success by minutes to half an hour or whatever it is, so it's quite fun. And I think as a couple you kind of like you know you share things and when you realise that you can go through this you can face anything in life. To be honest I'm practically off the tablets now as well. I take very few just to keep the body ticking but I find that my body's now slowly recovering.
PORTER
So you're getting back to the stage where you would have normal erections - normal erections without the need for viagra but it's there as a safety net?
KISSI
That's right and that's taken almost, let's say about 18 months, the journey to get there but it's a small price to pay for your life I think.
PORTER
Phil Kissi who is marrying his partner in September.
The Da Vinci system uses robotic arms to operate keyhole surgical instruments inside the patient. The surgeon sits at a booth - which looks a bit like an arcade game - in front of a 3D magnified picture of what's going on inside the patients, and uses a set of hand controls to move the robotic arms connected to the instruments. Surgeons using the system claim that is allows them to be much more accurate meaning quicker recovery and fewer long term complications like incontinence and sexual difficulties. Professor David Neal and his team at Addenbrooke's Hospital in Cambridge have done over 250 robotic prostatectomies. I joined them in theatre to see the system at work.
NEAL
This is a patient with early prostate cancer, whose disease was picked up because his PSA was high in his blood, had some biopsies and the disease is apparently localised to the right side of his prostate gland. There are a number of different treatment options that this patient had but for a variety of reasons he's gone for surgery and he's decided particularly to have this robotic prostatectomy. Big advantages are he'll recover more quickly, he'll get back to work more quickly, there's much less risk of bleeding and we think there's a better chance of preserving the nerves that produce penile erection and also preserve continence or urinary control. So when we are in the operation is we've been some ports in, which you can see over there, and the robot has these tiny little wristed instruments that go down the port, they're about seven millimetres long, you'll see them on the screen. And these can be controlled very, very precisely, so that I can move a millimetre closer to the prostate if I'm worried about the nerves or a millimetre away if I'm worried about the margin of the gland. And where we are right at the moment is we've exposed the prostate and we've divided the blood vessels that are running into the right hand side of the prostate and I'm just about to use some little metal clips to preserve the neurovascular bundle that runs down the back of the right side of the prostate that keeps penile erection going.
PORTER
And we're how far into the operation now, how long has it taken you to get to this stage?
NEAL
We're about an hour in and the robotic bit of the operation takes about two and a half hours, about three hours altogether. And it means we can do two a day, which is obviously ...
PORTER
And how would that compare, just in timings, to a conventional ....
NEAL
About the same actually, I mean two and a half hours. When we started off we only did one a day, it was much slower, and the operations were taking five or six hours to do. But we're now down to three, two and a half, three hours.
PORTER
I should point out at this stage that you're sitting in the corner of the operating theatre here, at the console, at the robot, and the patient's over to our left, a good three or four metres away.
NEAL
Could be even further actually, there have been cases done - trans-continental - I mean that's just a bit flash really, I mean there's no real reason to do it but I could be sitting in my office, that's my plan. But quite nice to do the surgery because you're relaxed and sitting down but when you start off you get terrible problems with your neck because the vision's so good - and you can have a look down here in a moment - your head automatically goes further and further into the machine and you end up with some strain at the back of ....
PORTER
Of course I mean you can stop and talk to me, you're sitting here not wearing surgeon's gloves, you're not scrubbed, you haven't got a mask...
NEAL
You're completely relaxed yes. No you can that's right, and you could even have a walk around ...
PORTER
No one mopping your brow.
NEAL
No, no that's all gone I'm afraid.
PORTER
Professor David Neal.
Important though advances in treatment like the Da Vinci system are, what doctors really want is a better screening tool that can reliably pick up early prostate cancers in men, and identify which need radical treatment, and which just require a watchful eye. Professor Roger Kirby.
KIRBY
I mean my view is that most men, especially those who have a family history of prostate cancer, over the age of 50 ought to know what their PSA is and ought to monitor it on a regular basis. That's not to say the government should screen every man in the UK but I think every man ought to know about it. And awareness of prostate cancer is definitely on the rise, there's almost - every week there's some article somewhere in the media about it or a radio programme. In the US, where 70% of men know what their PSA is, the rate of ....
PORTER
Compared to what in the ...
KIRBY
Six percent in the UK, 70% in the USA. What they've seen over the last 10 years is a four times greater fall in the number of prostate cancer deaths than - in the US as compared with the UK. I mean to me that means that PSA testing does reduce prostate cancer deaths but you know admittedly we know more studies, longer studies, which are in progress now to tell us for certain.
PORTER
So you're saying that men over the age of 50 should know their PSA but presumably that one off reading isn't necessarily going to be that helpful, so how often should it be repeated?
KIRBY
Well I have my blood test done, my PSA test done, once a year and - so I can construct my own personal PSA slope which for the moment remains low. If it blipped up then I'd definitely seek advice. So that's what I think people should do, not every doctor in the UK would agree with me but that's my philosophy.
PORTER
What about new perhaps sharper screening tools, is there anything in the pipeline?
KIRBY
Yeah there's some - whole series of new exciting markers in the pipeline to help us distinguish who does who does not have prostate cancer a. and who has the type of prostate cancer that we really want to diagnose early and treat, the so-called tigers compared with the pussy cats that might well be best left alone. So there's a new test that we've been using quite extensively called the PCA3 test, which is nice because it doesn't involve a biopsy and doesn't even need a blood test actually. What you do is you examine the prostate and you sort of stroke or massage the prostate - if I say to a patient would you like a prostate massage as compared with a biopsy they say oh I'll go for the massage please. So you massage the prostate, you collect the first five or 10 mils of urine that they pass immediately after that, which is a little cloudy because it contains prostatic secretions and then we send that off to the laboratory and they measure the gene, the PCA3 gene, which is over expressed in prostate cancer about 60 times, compared with normal. So we get that result back and then we have a much better idea of the risk of that particular individual harbouring cancer as opposed to having benign disease. We still have to do the biopsy often in the end, if the suspicion is high, but it means we can avoid unnecessary biopsies which is good for the patient.
PORTER
Could I elect to have that first, rather than the PSA - is it an alternative to a PSA test?
KIRBY
It's more expensive, it probably isn't an alternative, it's probably an adjunct, I mean a PSA test costs between £5 and £10 and it's just so easy to do and you can also add it in to cholesterol testing and so on which is useful in men. But the PCA3 test costs over £200, so we're a bit selective about who we use it on, we use it on patients who we think are at significant risk. You could ask for it and we could do it because it's reassuring to know that it's clear but you wouldn't want to do it on everybody.
PORTER
One of the criticisms about the practices in the States with so many men knowing their PSA is that there's a lot more men knowing that they've got prostate cancer, so they live longer with the disease because it's picked up that much earlier, do you think that's a fair criticism?
KIRBY
Well I think it is yeah and one of the worries is that as more and more men know what their PSA is more and more men get biopsies, more and more men get treated, so there's the risk that we may be over treating some of these men with the sort of pussy cat lesions who may never be destined to die from prostate cancer. So that's the downside. On the other hand the data from America suggests that PSA testing does pick up the more aggressive cancers and can reduce mortality. So it is a sort of swings and roundabout situation, there's no absolutely easy answer now and the studies that should clarify these complex issues are in place, so I hope if we did this programme two, three, four years down the line we'd be a lot closer to the answers.
ENDS
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