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| DR. PATRICK WALSH | |
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Dr. Patrick Walsh, director of the Jane Fucanon Brady Urological Institute at the Johns Hopkins Hospital, shares his thoughts on prostate cancer treatment and detection. The NewsHour Health Unit is funded by a grant from The Henry J. Kaiser Family Foundation.
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SUSAN DENTZER: What do we think causes prostate cancer?
More recently, there's been a lot of interest actually arising from studies at this institution looking at inflammation, and a whole story is developing suggesting that the prostate has a lot of inflammation, and that inflammation can lead to oxidative damage to the DNA, and the oxidative damage is then what begins to cascade for developing cancer. And we've actually identified two risk factors, two hereditary, high susceptibility genes, and you know what they do? Their normal function is to prevent infections. And so we may know someday that prostate cancer begins as an infection, which leads to inflammation, the inflammation leads to oxidative damage, and it is the oxidative damage that causes prostate cancer. |
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| The disease's progression | |||||||||||
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SUSAN DENTZER: You've seen many men with prostate cancer over the years. Give me a sense of the course of the disease, and I know that is also highly variable, so give me sort of the best case scenario, the man who has it for 30 years, he doesn't die of it, he dies of something else, versus the person in whom it progresses very rapidly.
Let's fast-forward to today. Seventy-five percent or more of men who present today have localized prostate cancer. The tumor is confined to the prostate, they have potentially curable disease, and they have many different options. Now, the problem we have today is when we see such a patient, we cannot accurately predict the natural history of that disease. We have some parameters. If the patient's [prostate-specific antigen test results are] very low, if it looks like it's slow-growing and on examination if you cannot feel the tumor, those patients have tumors that may, with just watchful waiting, progress over the next 10 to 20 years. The higher the PSA, the more aggressive the cancer under the microscope, the Gleason Score, and the more palpable the tumor, the natural history of that disease then truncates. So over the next five or ten years, that disease can progress to a lethal disease. And then you add in age. So if you take a 40-year-old man with almost any form of prostate cancer, he is going to live long enough to develop progression of the disease. Indeed, in Scandinavia, in men under the age of 55 who were treated with watchful waiting, eventually 100 percent of those patients died of prostate cancer. So you not only put the tumor and its aggressiveness into the equation, but also the host and his health and age. SUSAN DENTZER: Give me a sense of what kind of death this is for prostate cancer. What stages does the patient go through, and how painful a death is it relative to the other cancer deaths that we know are extremely painful -- lung cancer and bone cancer, for example.
The uncle who raised me, who was very important in my life, died a painful death from prostate cancer, and I watched him hooked up to a catheter in his bed, in his living room, for a year, dying of prostate cancer. It's a terrible, terrible way to die. |
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| The value of screening for prostate cancer | |||||||||||
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SUSAN DENTZER: When people raise concerns about PSA testing and point to this high false positive rate, how problematic is that, in your view, that indeed very often it indicates that something is going on, but not cancer, and it causes a lot of concern that may not be able to be addressed?
If a woman has a positive mammogram, her risk of having breast cancer is 16 percent. If a man has an elevated PSA, his risk of having prostate cancer is 35 percent. So as we get better and better screening tests, and we want to lower the sensitivity, so we pick up all of the tumors, we don't miss any, we obviously are going to have more people that don't have the disease who are accidentally diagnosed. And I think that the performance of PSA vis-à-vis mammography is actually better. SUSAN DENTZER: Do you agree, though, that the evidence is not in yet, that we can show a clear correlation between screening and reductions in prostate cancer mortality? PATRICK WALSH: The answer is there hasn't been enough time to show the value that I truly believe is there. What we've been able to show is that since screening came in, fewer men present with metastatic disease. More men present with curable disease. More men are being offered curable therapy, and deaths from prostate cancer in the United States have fallen 30 percent. In the early 1990s, 44,000 men died. This year 30,000 men will die. And if you look at the countries that have experienced this decrease in death rate, they are the countries that have been aggressive in terms of diagnosis and treatment -- Canada, Germany, Italy, and the United States. If you look at the rest of the world, prostate cancer deaths are going up 1 to 2 percent a year, an epidemic of death from prostate cancer. So all of the circumstantial evidence points to the fact that there is accumulating evidence that it is going to work. The randomized trials, which are the gold standards, are not in yet. But if you look at all of the other information, it's very circumstantial. As a matter of fact, this year the American Cancer Society strengthens its recommendation by saying men should not be discouraged from having testing, and if a man requests testing, he should be given it. SUSAN DENTZER: The [Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial] trial results probably will not be in until 2010 or sometime thereafter. What do you think that they will show?
The screening interval, I think, between the first PSA and the second one was too long. And once a man was diagnosed with prostate cancer, there was no requirement that that individual needed to be treated for prostate cancer. And the end point is going to be prostate cancer deaths. So if you put in men who are not going to live long enough to die from the disease, if you don't screen at appropriate intervals, and then when they are diagnosed with cancer, if you don't mandate treatment, I don't think it will ever be a positive trial. The best breast cancer screening trials, the mammography trials, many of them have been positive and not all of them, but all of those women underwent active treatment. The PLCO did not require that. |
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| Patients' choices after diagnosis | |||||||||||
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SUSAN DENTZER: All right, let's talk about two issues that arise, again, if someone has an elevated PSA test, has a biopsy that then does indicate that there is cancer present. As we were saying earlier, for some people, watchful waiting is a reasonable course of action. But some men say, "But then I'll know that I have cancer. And even if I decide to live with that and do watchful waiting, I'll have this shadow over my head. I'll have this sense that I have a cancer, I'll have the sense perhaps of impending doom, and I'll be perhaps even stigmatized as a cancer patient. That's something that I don't want to know." Is that a reasonable response, and do you find patients working their way exactly through that set of concerns?
That recommendation's been standard, and when you tell those patients that right now this cancer is slow growing. I don't think we have to do anything, they'll say, "Thank you, Doctor. I'd hoped you would say that." So that's the side of it that I hear. The patients that you just talked about who are very worried about it probably have something to worry about. If they're not in that category, and if they have a significant cancer on biopsy, they have every reason to have that worry. Now, previously, that worry could be countered by saying well, there's no evidence that treatment of prostate cancer will reduce your chance of dying from the disease. But now that question has been answered by the gold standard, a randomized control trial in Scandinavia. Seven hundred men were enrolled in this trial that was carried out since 1988, randomized to either watchful waiting or surgery, and I think the results are dramatic. As early as eight years following treatment, in men who underwent surgery, progression to metastatic disease and bone, and death from prostate cancer was reduced 50 percent. So I think today we can say to patients who are going to live long enough to have the consequences of it that treatment definitely can reduce their risk of dying of prostate cancer. So I think patients now have to add that to the equation. Okay? I have a cancer that is significant, and there are definitions of what a significant cancer are, and I'm going to live long enough to run the risk of developing progression of disease. Now, given those facts, some patients will still say, "I don't want to be treated." And the important answer to all these questions is the final answer should be what an informed patient wants to do. It's not what a doctor tells him to do. SUSAN DENTZER: What happens in the course of radical prostatectomy surgery? What do you do?
The operation is one of the most technically challenging operations in all of surgery. I'm not trying to underestimate it. There are major veins that travel over the prostate that must be controlled, so one is operating in a bloodless field. There are the delicate nerve bundles that run on the lateral surface of the prostate, and the surgeon must use good judgment about whether these nerves can be preserved or excised to remove all of the tumor, and in preserving them using precise techniques to be sure that they're not damaged. So it's an operation that is challenging, and it's best done by an individual who does a lot of them, who specializes in it. SUSAN DENTZER: If a patient is sitting out somewhere in Podunksville, maybe is in an HMO that will not let him go anyplace other than his local community hospital, looks at the statistics saying if I get a radical prostatectomy, there's a 60 percent chance I'll be impotent, that's a different equation than if you're sitting right here able to go to Hopkins or someplace else; correct? PATRICK WALSH: It is. And what I find when patients say to me well, how do I know how good my doctor is, and what should I do, I think that most urologists in the United States are very honest with their patients, and I think the patient needs to ask his doctor what are my chances of being cured how often do you have to give radiation to people and hormones afterwards because it's possible that maybe an operation isn't the best treatment form if the tumor is too far advanced. And what are your results in patients just like me in terms of continence and potency? And if they are not as good as they should be, then that person needs a second opinion. They need another doctor. And very commonly, that urologist himself or herself will say well, the person who I would suggest you see is this doctor. If they cannot get that advice, they should go to their HMO. They should present the information saying I cannot get the best form of treatment, I need to find someone else. There was a case a couple of years ago that was widely published in the L.A. Times where someone who was in Kaiser Permanente could not get that information, and Kaiser Permanente permitted that person to go up to Stanford to someone who I trained to have his operation, and he had an excellent result. And I think if that becomes more commonplace, that people are empowered to do that, to say if they were going to have brain surgery and they were told that they would be in a coma for the rest of their life, they wouldn't accept that. And I think if a person who is young and healthy, and in whom surgery seems to be the best option, that they ought to have the availability of someone that does this operation well. |
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| Assessing the value of screening | |||||||||||
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SUSAN DENTZER: Some people who are looking at the screening and who are basically bio-statisticians, look at this issue from one perspective, and acknowledge that where you stand on the issue screening depends on where you sit. You're a person who treats men who come in with cancer. Perhaps you believe, as we have found is the case with breast surgeons that believe much more strongly in mammography than the bio-statistician looking at studies about it. Does that play a role? Does your personal experience of this disease play a role?
We had no marker for it before, and if you ask patients who have prostate cancer what do they think of the PSA test, they think it's a godsend. No one would ever know they had cancer. Some of these cancers also are very extensive. They are life-threatening cancers. These are not small, slow-growing tumors. They would never have been detected without PSA testing. SUSAN DENTZER: So from your perspective, it's a slam dunk.
But the vast majority of men that I see who are diagnosed with cancer are diagnosed at a curable stage. They then can, at this time in their life, look at the picture that they may not have looked at before, evaluate their options, and make an informed decision. They know very well whether they're curable or not, and how do they want to approach it. I find it very refreshing, and what's fortunate about it is today so many men are presenting with curable disease. |
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PATRICK
WALSH: Well, there's a lot of speculation about it. We know that men
that are Asian and grow up in Asia have a 2 percent lifetime risk for
developing the disease. But when they move to the United States and
live here for 25 years or more, their risk begins to approach that of
Caucasian men in the United States. So it has something to do with environment,
either things that we do wrong in the United States like possibly eat
too much fat, or things that we don't do at all like not eating enough
green tea and soy.
PATRICK
WALSH: Well, you've pointed out that prostate cancer has a varied natural
history, and let me give you two different eras. Let me talk about the
1980s. When a man with prostate cancer came in to see me in 1980, he
had a 75 percent risk that that cancer had already spread outside the
prostate, and we could identify that clinically, either because we could
see it on a bone scan, or locally the tumor had extended outside the
prostate. And in those days, very few men were curable.
PATRICK
WALSH: Well, I think prostate cancer is up at the top of painful cancers
because when prostate cancer progresses, the major site it attacks is
bone. It doesn't attack the heart, the lungs, the kidney and the brain.
And so patients do not have some vital organ wiped out. They develop
progressive disease in bone, develop severe pain, and a death that can
go on for one or two years.
PATRICK
WALSH: Well, when I hear that, I really point to the gold standard.
I point to mammography, and I say here's a gold standard test that everyone
accepts. Now, let's take a 50-year-old woman and a 50-year-old man,
and both come home the same day with bad news. The wife's mammogram
is positive, the man's PSA is elevated. Who has the greater risk of
harboring a cancer? It's the man, and his risk is twice as great.
PATRICK
WALSH: I don't think the PLCO study will be a positive trial, and I've
been an outspoken critic of it ever since its inception...
PATRICK
WALSH: Well, the entire prostate is removed, and along with it, the
glands that are attached to it, the seminal vesicles. You are then left
with the urethra and a bladder neck that have to be connected together.
PATRICK
WALSH: Oh, it absolutely does. I mean, I used to hate to go to clinic
back in the early 1980s because you would see all these young men who
came to you for surgery, and they weren't curable. And today you see
an entirely different story. Virtually everyone you see is curable.
It's because the disease is being picked up at a curable stage.
PATRICK
WALSH: Well, it's not necessarily a slam dunk. I mean, I see the other
side of the story too, and I understand fully that there is a cascade
of events that occur. Some patients will undergo diagnostic procedures
they do not need. Some patients will be diagnosed with cancers for which
there is no treatment necessary.
