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Prostate Cancer: Evidence-Based Approach to Screening and Treatment
UPMC urologist, Dr. Joel B. Nelson, presents the pros and cons of prostate cancer screening. This presentation was part of UPMC’s Update in Internal Medicine 2010: Evidence-Based Approaches to Common Medical Problems.
Learning Objectives:
- Articulate the pros and cons of screening for prostate cancer
- Describe the importance of active surveillance in disease management
- Develop a more informed screening and treatment protocol
Disclosure: Dr. Nelson is a consultant for Astra-Zeneca, AmGen, Millenium/Tekeda, Roche Diagnostics, Bayer Healthcare, Centocor, Orthro Biotech, Atlab Pharma, and CARIS.
Accreditation Statement
The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The University of Pittsburgh School of Medicine designates this educational activity for a maximum of .5 AMA PRA Category 1 CreditsTM. Each physician should only claim credit commensurate with the extent of their participation in the activity.
Release Date 2/14/2011 | Review Date 2/14/2012 | Expiration Date 2/13/2013
Transcript
Thank you very much, it’s really, it’s a pleasure to be here this afternoon and talk to you about prostate cancer and I wish, wish I had an easier topic. The, the title of this symposium is Evidence Based Approaches to Common Medical Problems and you’ll see at the end of my talk that prostate cancer in fact is quite common. And we have evidence that seems to point in opposite directions and I’m going to try to bring some clarity hopefully to some of the data.
I think the problem with prostate cancers was summarized very nicely by Willet Whitmore, who really was the grandfather of urologic oncology, and he unfortunately actually died of prostate cancer, which is if cure of prostate cancer is necessary is it in fact possible? And if cure is possible, is it necessary? And I’m going to focus most of my discussion today on the second part of this conundrum a riddle wrapped up in a, in a pun about how we try to manage what we think might be disease that doesn’t need to be treated.
These are the data from the American Cancer Society for new prostate cancer – or new cases of cancer in the United States, and you can see that prostate cancer continues to be the most diagnosed cancer in U.S. men, accounts for almost 1/3 of the cases, and at the current rates of diagnosis it’s still about 1 man in 6 in his lifetime in the United States. We expect about 220,000 new cases this year. And unfortunately it continues to be a very common cause of death from pros – from cancer in the United States, number two only to lung, and if we could eliminate smoking that would probably move into first place. And this will work out to about 32,000 men who will die of prostate cancer this year. So we have a very commonly diagnosed cancer which unfortunately also results in death for some men who are found to have it.
You can see the effects of PSA screening as we look at prostate cancer incidents, so you can see that before there was PSA the rates of diagnosis of prostate cancer were largely done at the time of TORP or on digital rectal exam, and when PSA emerged in the middle ‘90s there was a huge spike in the rate with which we diagnose this disease. I found it somewhat amusing when I heard Rocky say, you know, if we do more colonoscopies we’ll find a lot more cancers, well look we did a lot more PSA tests and we found a lot more cancers and I’m not sure it’s all good. You can see that we eliminated a lot of cases that were sort of in the background, but since PSA has been around we’ve never retreated back to the rates with which we had diagnosed prostate cancer in the past.
The good news is that the death rate from prostate cancer, as is the case with many solid tumors, has declined. And this is in the face of an at risk population that’s aging, so the Baby Boomers are now just coming into the age where prostate cancer will be diagnosed and we expect that if all things being equal the death rate in fact should be going up, not going down. But that’s not what we’ve been seeing, in fact we’ve seen a decline in the death rate from prostate cancer since PSA screening has begun.
Well isn’t this all very good news? Yes, it is good news and when I was a resident before PSA came around roughly ¼ of all men to came into the hospital with prostate cancer had metastatic and often symptomatic disease. That now accounts for less than 2% of all the prostate cancers that we see. So in the pre-PSA era only less than half of our patients came in with what would be considered to be clinically localized and curable disease, and more than half had advanced or locally advanced disease. Today over 85% of patients diagnosed with prostate cancer have clinically localized prostate cancer, and this we would argue is very good evidence of the effectiveness of screening for prostate cancer. Unfortunately it brings with it a lot of luggage. You can see that the, this is borne out and you look at population based studies, this is something known as the capture database which is a combination of both academic and community practices looking at the type of cancer that walks into the door and over this period of time to 2002 high risk disease has decreased significantly, and at the same time there has been an increase in what we consider to be low risk prostate cancer.
Well, society is beginning to wake up to the fact that so many men have the diagnosis of prostate cancer and in fact earlier this year on the wire the American Cancer Society made this declaration that perhaps we should stop offering our patients PSA testing or perhaps let our patients decide whether they in fact want to be screened for prostate cancer. And we’re even seeing things like this, which just was published, the Invasion of the Prostate Snatchers. Isn’t that a great title? No more unnecessary biopsies, radical treatments or loss of sexual intimacy, and this was written by a team of both a, a, a long term prostate cancer survivor who has had no real definitive therapy, he probably has disease that is you know going to be autopsied like, and then a physician. But really what they are trying to point out is that we as urologists and as people concerned about prostate cancer have put on blinders and viewed every one of these sort of in the same way, and shouldn’t we in fact be more stratifying in our approaches to this.
Well, the problem really doesn’t begin with urologists, by the time you send a patient to us we are more or less along a path that’s already begun, and that is that the patient has some reason to be in our office, i.e. either there’s been an abnormal exam or more likely an abnormal PSA test. And so really this is a question for primary care doctors like you all, which is that should we be screening for prostate cancer?
Well what are the downsides of screening for this disease? The first is, and this remains true, most prostate cancers actually are remarkably latent, so next time you walk into a nursing home and see a bunch of men that are 80 or 90 years old recognize that almost all of them have histologic prostate cancer but don’t need to know it, and in fact we never would treat that. The very test we use to diagnose prostate cancer, PSA, is elevated artificially in about 2/3 of the men who have an abnormal PSA. So even though I’m at the end of a long funnel, only about 40% of the biopsies I perform are actually positive for prostate cancer, meaning I’m doing a lot of biopsies in people who don’t have the disease.
And there has not yet been consistent definitive level one evidence that prostate cancer screening reduces prostate cancer morbidity and mortality. And the key in that sentence is the world consistent. Prostate cancer treatments are clearly harmful, we would love it if we didn’t bring men to their knees with erectile dysfunction and loss of, of continence. Screening clearly is morbid, biopsy is nothing anybody wants, and it leads to more studies, and this is very costly if you assume one man in the United States needs to be treated for – 1 out of 6 needs to be treated for prostate cancer in his lifetime. Well why would we in the face of that ever screen for the disease? Well you want to screen for things that are common, prostate cancer is common, and you want to screen for things that if you don’t detect them in an adequate period of time the patient might die, and prostate cancer as I pointed out is the second leading cause of death from cancer in the U.S. And it’s still true unfortunately that effective treatment is limited to localized disease. So men with metastatic prostate cancer, if they are young and they are healthy they will die of prostate cancer, and that unfortunately is still true today.
PSA is effective, it’s not perfect, but clearly it’s the best tumor marker far and away of any tumor marker that exists is the PSA test. So yes, it picks up things other than prostate cancer, but it is actually the rate cancer that you can miss by having a PSA test. And it very much picks up the disease we want to pickup that is localized and early disease when it’s curable. And the – finally when I argue about whether we should screen or not I ask the people I’m arguing with have you ever had a patient die of prostate cancer? I mean it is awful because they don’t die right away, it’s a very long and painful process. And so if you could avoid that fate, even if you have to put yourself at risk for some of the side effects of our treatment, I think it’s – it has some merit.
Does anybody know who this is?
Will Rogers.
Very good, you know when I ask the residents this question, when I give this talk to residents, they have no idea. So you are showing your age. So Will Rogers was famous for his dislike of people from California when he said when the Okies left Oklahoma and moved to California they raised the average intelligent level of both states. And this is what we refer to in medicine as stage migration, and this has clearly been evident in prostate cancer. So if you look at situation 1 here, that is before we had PSA screening patients would present usually with somewhat advanced disease. We would intervene, not very effectively, and they would go on to die of their disease, and their survival time was maybe 10 or 15 years. Now with PSA screening we pickup their disease, assume we still don’t have effective therapies, which isn’t in fact true, it looks like they are surviving much longer. But all we’ve really done is labeled that patient with prostate cancer at a point in their life where they are going to live longer and then eventually die of the disease. So clear evidence of lead time bias. And we have to recognize that the improvements we’ve seen in prostate cancer management are somewhat overlaid with this problem of knowing that we are picking up disease much earlier than we used to.
This is a little bit busy but I think it’s worthwhile walking through it. If you look at patient 3 here, who has an advanced, or has a lethal form of prostate cancer, screening is introduced by these two screening episodes would fail him. In other words, his disease would go from microscopic to metastatic so quickly that the only screening regimen would have to likely be weekly to pickup his prostate cancer. And on the other end of the spectrum, patient number 1 is never destined to die of prostate cancer, in fact doesn’t have a prostate cancer you actually need to diagnose, so screening of that patient you might pickup as disease but that’s not going to change its natural history. And patient 2 is really the world that I live in, which is these are patients we believe when we screen them in fact the introduction of effective therapy changes the natural history. That is that is somebody who otherwise would have gone on to die of prostate cancer and by introducing effective therapy we in fact allowed them to die of another cause.
Well, the question about screening has been very difficult to answer because in the United States screening is done widely, but in Europe PSA screening in particular was not done at all. And so a, several Europeans from a number of countries, 8 different countries in Europe got together and decided to sort of pool their resources and do the definitive screening study, which was published in 2009 in the New England Journal of Medicine known as the European Randomized Study of Screening for Prostate Cancer. And the primary end point was a good point, that is would we have any impact on prostate cancer mortality, not prostate cancer progression or prostate cancer recurrence, but mortality. And that is comparing a screened population to a non-screened population. The study started in 1991 and all patients were enrolled by 2003 in 8 different European centers which happened to also be in 8 different European cities. They included the at risk population, men 50 to 74, and the screening interval was really not quite as rigorous as it’s applied in the United States with annual tests, but it was applied every 4 years or every 2 years depending on the country one lived in. And then biopsies were recommended for anybody who had PSA’s over 3, again a slightly lower threshold than what we would apply in the United States.
This was a huge study, so the screened and control arms are not exactly the same because in Finland there was a lot of belief that screening was bad so they randomized 1 ½ to 1, but be that as it may the screened arm was 72,000 and the control arm was nearly 90,000. There were a large number of screening tests done, over 126,000, and 20,000 of these patients, about 16%, remarkably close actually to the rates with which we find prostate cancer in the United States, were positive.
And European mean actually were pretty compliant with going onto the next step, that is having a biopsy, something very different than you’ll see in the study I’ll talk about from the United States. So 85% of European men who had an abnormal screening actually underwent a biopsy to determine in fact if they had prostate cancer. They found 4,000 cancers, the predictive value of a biopsy is about 25%, which is pretty close to what we see in general urologic practice, if you simply biopsy people who walk in the door at risk. And the follow-up of this study median was 9 years, a point I’ll return to. This is simply the schematic.
What did they find? Well, not surprisingly, if you screen for prostate cancer you’ll find it, in fact you'll find it at a rate that’s almost twice as common as if you don’t screen for it. So they found it, the prostate cancer detection rate in that population of 8.2% compared to 4.8 in men who simply showed up with usually more advanced disease. And the number of deaths that occurred also was lower in the screened arm, 214 to 326. It’s amazing though that you have to start with about 90,000 men and you only have 326 at the end, it speaks to the challenge that we face in managing this disease. And if you look at it in the attempt to screen analysis, 20% fewer men died of prostate cancer if they underwent screening, and if in fact they were compliant with the screening that went up to 27%, and this difference was in fact significant.
So what’s the absolute risk reduction? That is if you are sitting across from the patient and you say well, how many people do I have to screen to actually show a difference? It turns out that you have to, you can, you can save the lives of 7 men if you screen 10,000. Which mean the number needed to screen is about 1,400. And if you were to look at who needs to be treated to prevent one prostate cancer death, and this is the figure that’s really been picked up quite a bit in the popular press, in this study you had to actually screen and treat 48 men to save one man’s life from death from prostate cancer.
How does this compare to mammography? I’m not a breast cancer specialist by any means so I simply went to the literature, but here in one study the number needed to screen over 5 years in women 50 to 59 is 2,400, very similar to what we seen with prostate cancer. So the complaint that prostate cancer screens unnecessarily is not so different than what we see with mammography. And frankly, it’s not so different from what the data you just saw for colonoscopy.
I think the other important element of this issue of one has to be – one is safe for 48 treatment, that is a time dependent variable. So again looking at the breast cancer literature, if women have high risk of developing breast cancer given a family history and they decide to undergo prophylactic mastectomy as the way to manage the high likelihood they will develop invasive breast cancer, you can see that death from breast cancer at 10 years you would have to, you would have to do bilateral mastectomies in 44.8, but as you move farther out, now at 15 years the number that you would need to treat drops to 25. So really when you hear that number 1 in 48, that’s at 9 years. When I see men with prostate cancer I tell them look at, the reason I’m going to operate on you today is not because you are going to die in the next 10 years, it’s because I want you to be alive 20 and 30 years from now. And in fact if you are not going to be alive for other reasons in 20 or 30 years from now, we should be very circumspect about whether in fact you should be treated.
Here are the Kaplan/Meyer type analyses, it’s actually not a Kaplan/Meyer, it’s a different statistic, but you can see that, that the separation of these two curves in this study at 9 years was pretty trivial, but as you move farther out you can see the, the excess number of deaths increased in the control arm compared to the screening arm.
One of the strengths of this study is that there was no heterogeneity by center, so each country had the exactly the same result roughly, and that was about a 16 to 26% reduction in prostate cancer mortality, which means that this wasn’t driven just by the Netherlands or just by France, this was driven by the com- the combination of all the centers.
Okay, well that’s great for the Europeans, we live here in the United States, and in the United States prostate cancer screening and particularly PSA screening is widely conducted. In this study in 2003 in JAMA at every age group PSA screening was more common than colonoscopy, for which there is actually good evidence that in fact you should recommend colonoscopy to your patients. So we live in a world where PSA is already out there and widely done. And if you ask practicing clinicians, and I’m sorry it’s small but I believe it’s in your hand-out, you can see that most practicing clinicians in fact would recommend that screening be offered to men over the age of 50, and only a minority feel that it shouldn’t be offered at all to patients who are over the age of 50. So our general practice, and this is now you know family doctors and internal medicine doctors think that this is a good thing to do.
Well at the very same issue of New England Journal of Medicine where the European study was published, this study was published, which asks the same general question in an American population. And they took advantage of the prostate arm of the so-called PLCO study, which is a screening study looking at an end point very similar, that is does screening for prostate cancer reduce mortality in a non-screened, that is within the auspices of the PLCO study as compared to a screened arm within the auspices of the PLCO study? This was in the same time period, ’90/’93 to 2001 at 10 US sites. It’s about half the size of the European study, same general age groups. The screening here was more an American flavor, that is annual digital rectal exam and annual PSAs. Very much unlike European study though, if anybody screened positive they were sort of sent loose into the usual care of their community. These are the PLCO screening sites. It turns out the University of Pittsburgh where we are here was one of the sites. And not unlike the European study you can see that if you screen for prostate cancer you’ll find it more commonly than if you don’t screen for it, and that’s clearly shown here over time. But very different than the European study, in America screening for prostate cancer over 7 years has no impact at all on prostate cancer mortality.
Well what are some of the problems with the PLCO study and why have I said very frequently in public I can’t believe this actually got published in the New England Journal of Medicine? The first is that because PSA screening is so widely done in the population in the 3 years up to going into the study roughly a third of men had already undergone PSA screening. That immediately removed from the population everybody who has a bad prostate gland, or the third of men who had screening, if you were destined to have cancer, so you have healthier men in the screening population, healthier prostates that is.
The second problem, which is the major problem is that the control arm, the arm that wasn’t supposed to be screening in fact was screened at very high rates. So within the first year these guys just went across the street to their family doctor and said look, I got randomized to the arm in the PLCO where they are not going to do a PSA but my neighbor got prostate cancer, can you just draw PSA on me because I’m a little nervous about this? And by the sixth year of the study half of the patients who weren’t supposed to be screened in fact were screened. The final problem with the study is that these patients told you have something wrong, only about 40% of them actually proceeded to find out what their problem was. So if you are going to – nobody thinks that doing a digital rectal exam and doing a blood test is going to save anybody’s life from prostate cancer, you actually have to intervene on that information. And so the follow-up is really pretty weak in this study, very much unlike the European study. And then they are only looking at data out 7 years, I really think none of us would have expected any difference at 7 years because you are talking about a slow growing cancer. This isn’t like pancreatic cancer or glioma where you are going to get your answer quickly, this is one you have to look out 15 to 20 years to see what the differences are. And I just point out to you that at 7 years in the European study there was no difference at all between the screened arm and the control arm, so the PLCO study shows us the correct data, but the follow-up is simply too short as supported by the European study.
And I think I’ve made these points significantly, so is there evidence that we should do prostate cancer screening? Yes. In one study there is level 1 evidence that screening reduces the risk of dying of prostate cancer by 20%, and if you are compliant with your biopsy it’s 27%. However we have to add that this is in men age 55 to 69 who happen to live in Europe, so those of you that want to emigrate to Europe you should go get screened. That comes at I think a considerable risk of potentially unnecessary treatment.
The other answer to the question would be no, actually in fact in the United States there is no reduction in death from prostate cancer in a 7 year follow-up period of time, in a more intensively screened group compared to a less intensively screened group. So for your patients I think the honest answer is if I’ve ever done a PSA test for you, what’s the likelihood that PSA tests is going to do today in terms of saving your life from death from prostate cancer in the next 7 years, it’s you have to say there is no evidence this is going to save your life in the next 7 years.
Well what should we do with our patients? The American Urologic Association of which I’m a member took this information and said aha, we should be doing exactly what we said we should be doing, and that is in fact we should be screening even starting at the age of 40 because the people that really have a lot to lose to prostate cancer are the young men, so this morning I operated on a 44 year old, and I felt very good about it because I know untreated he was going to die of prostate cancer, because he’s so young, he’s got to live for another 40 years. On the other end of the spectrum, the American Academy of Family Physicians feels that there is really insufficient evidence on which to recommend for or against routine screening for prostate cancer using this PSA test and a digital rectal exam. So here we are sort of stuck between the two polls.
I just want to tell you that there are some things you need to remember about PSA testing, that is that the idea that the number 4 and above is wrong, and the number of 4 and below is okay, you need to forget that. That’s not true. So in this study that looked at the use of Finasteride or Proscar, excuse me, I didn’t say that, Finasteride in chemo prevention at the end of the study about 3,000 men underwent a biopsy. They didn’t have anything else to suggest they needed it, but it was the study design. And what they found was that if you had very low PSAs you still had a reasonably high chance of being found to have prostate cancer. And if you look at the cohort with the PSA from 3.1 to 4, almost 27% of those patients if you simply stuck a needle into their prostate gland you’d come across prostate cancer. So you can’t believe that if somebody’s PSA is 2 there is no chance they have prostate cancer. In fact in this study if your PSA was 2, you had about a 25% chance of having prostate cancer.
The other thing to recognize is that young men should have low PSAs and older men can have higher PSAs, and the race of your patient actually something to say about what would be considered normal or abnormal, and this is in your hand-out. Asian men, African-American men and Caucasian men all have different age specific PSA ranges.
I’m asked regularly by defense attorneys mostly to try to defend medical doctors who have been, are being sued because they didn’t diagnose a prostate cancer. So what are some of what I think are avoidable pitfalls? If you have a discussion with your patient about whether or not you should screen for prostate cancer and you actually document that in a medical record, I don’t see that you are – there is any problem. Because if you say and the patient agrees that they are not going to be screened for prostate cancer, we can all bring out all kinds of data that would indicate that in fact that’s appropriate. To not have a discussion puts you at some liability.
One that I’ve seen repeatedly is that people just don’t like doing digital rectal exams. And I don’t like doing them either, but I have to, right? So you can’t just rely on a PSA test because some prostate cancers in particular the really bad ones stop making PSA, and you can only pick them up by actually feeling the exam – the gland.
And then obviously things like an abnormal test just gets dropped on the end of the lab slip and you don’t pay attention to it, or somebody has a change in their PSA that somebody in hindsight would say boy, you should have done something about that. Also deciding to do a PSA test every 5th year or every 6th year, unless you can support that you are really on pretty shaky ground. And I think that the uncertainty about screening really should not allow you to be silent or to do an incomplete evaluation. So if in fact you are going to screen for prostate cancer do it correctly, annual PSA, digital rectal exam, age 50 until that patient has a less than a 10 year life expectancy, earlier if they have family history or African-American race.
Well what about those of us that treat prostate cancer? And if you pose it to those clinicians, you have a young man, he’s healthy and he has low risk prostate cancer what would you do? And you can see that the radiation oncologists have all the things they like to do, brachytherapy, external beam, 3-D conformal, surgeons we would say take out his prostate gland, but unfortunately only a fraction of physicians who manage prostate cancer are actively in involved in simply observing men with prostate cancer, and I think this needs to change. And let me give you some evidence on why.
So my colleague, Laurie Klotz, who lives in Toronto, and I’m quick to point out this is a Canadian study where healthcare delivery is very different than it is in the United States. This study where he took 450 men and he put them on active surveillance, now let’s be clear about the language here. What active surveillance means is that you are still going to potentially intervene on that, on behalf of that patient with curative intent when their disease progresses. That’s different than watchful waiting. Watchful waiting says no matter what happens with your prostate gland the only intervention we are going to apply is going to be palliative, watchful waiting is generally done in the 80 year old men, active surveillance in men who still have some risk of death from prostate cancer.
So this Canadian cohort, he followed this patients a median of 6.8 years, and these were men that we would expect would be appropriate for an active surveillance protocol, they were old, 70 median age. And interestingly at 10 years of follow-up the proba – the overall survival of this population was 68%. And that pretty much approximates a death curve, right, 70 year old men, 10 years later 80 year olds, you expect about 40% of them are going to die. But quite interestingly the cancer specific survival at 5 and 10 years was 99 and 97%, so very, very few of these men selected for active surveillance actually died of prostate cancer.
And if you look at the mortality, all cause mortality versus prostate cancer specific mortality, the hazard ratio was 18. So when I see a 70 year old man who has low risk prostate cancer and he says well if I don’t get treated what’s the likelihood I’ll die of prostate cancer? I say it’s about 20 times greater you are going to die of something else. And if you stratify by age and you look at men over, over the age of 70 the hazard ratio for death from another cause is 33 to 1. And if you are under that age, it’s now something where we begin to get a little nervous, it’s only about a hazard ratio of 8.
What’s the likelihood you actually could stay on surveillance? Well if you die you are obviously not going to stay on surveillance, so most of this curve is just driven by death from another cause. Remember at 68, at 10 years 68% of the patients had died, so only 6% of the patients at 10 years had actually undergone some intervention. Why? Well most it was due to changes in PSA kinetics, and this is a very controversial area in our field so I can’t say that there is consensus about this.
One of the criticisms of the Klotz study and active surveillance in general is that if you watch a patient long enough and then decide to intervene your intervention is not going to be nearly as effective as it would have been had you applied it earlier. And you kind of want to say da, of course. I mean if I would have treated this patient when he walked in the door I would have cured him. And if I watch him, the likelihood of cure goes down, but that’s the risk you explain to the patient. The truth is that many of these men never need, will never need to be treated so they can avoid it completely. But if I were to show you these data for either radiation or surgery in newly diagnosed patients, the results are going to look much better than they would look in this population where you sort of selected for the progressive diseases, progressive tumors.
This has been supported, his observations have been supported by what now is considered sort of a landmark and somewhat historic study where men in Scandinavia were randomized to either get watchful waiting, that is no treatment at all and only androgen deprivation at time of progression or radical prostatectomy. And this is a very interesting set of curves that were updated 2 years ago in GNCI. The overall mortality for men who underwent watchful waiting over the age of 65 was identical to the men who underwent surgery over the age of 65, and the only people that really seemed to have a lower overall mortality was if they had surgery and they were under the age of 65. And the congress of this, supporting it is that the only population that had an excess death rate from prostate cancer were in young men who in fact did not get treatment. So based on data like these, we really think that we are moving into the, the age where we are going to be very selective about who we should recommend treatment for prostate cancer. That doesn’t mean we don’t manage their disease. You can’t cure diabetes usually, but you manage it, right? Well you can’t necessarily cure prostate cancer, but if you are not going to die of the disease, you just manage it, you observe it and you only intervene when it’s necessary.
So what are my conclusions? The lack of consensus on prostate cancer screening does not equate to silence on the issue, and I think it’s important since you all are really on the front line, again by the time they get to me, I mean we are sort of obligated to investigate. You need to understand what the nuances of it – of this issue are. I think there are clear results from our widespread screening and that is that there is overtreatment of prostate cancer, and I think we are going to need to be increasingly sophisticated about who we apply treatment to. But on the good side there has clearly been a decline in late stage disease, and we expect that in fact the death rate from prostate cancer will continue to go down even in the time when the at risk population is growing older.
And finally, a prostate cancer diagnosis no longer should be monosynaptic, I’ve got to treat you, right? You need to have a discussion with the patient, if it’s high risk disease yes you need to be treated, but for low risk disease in an older man I think that often the best way to manage that patient is to sit him down, tell him look, prostate cancer has the wrong last name for what we’ve found in you. It’s something in your prostate that we need to take care of, but it’s nothing that’s really going to harm you. And I think that’s my last slide.
Before I thank you I also want to say, and I know this is somewhat impersonal, I think I got the opportunity to take care of many of your patients over the last 11 years and it’s been really an honor. Thank you.
Thank you very much, it’s really, it’s a pleasure to be here this afternoon and talk to you about prostate cancer and I wish, wish I had an easier topic. The, the title of this symposium is Evidence Based Approaches to Common Medical Problems and you’ll see at the end of my talk that prostate cancer in fact is quite common. And we have evidence that seems to point in opposite directions and I’m going to try to bring some clarity hopefully to some of the data.
I think the problem with prostate cancers was summarized very nicely by Willet Whitmore, who really was the grandfather of urologic oncology, and he unfortunately actually died of prostate cancer, which is if cure of prostate cancer is necessary is it in fact possible? And if cure is possible, is it necessary? And I’m going to focus most of my discussion today on the second part of this conundrum a riddle wrapped up in a, in a pun about how we try to manage what we think might be disease that doesn’t need to be treated.
These are the data from the American Cancer Society for new prostate cancer – or new cases of cancer in the United States, and you can see that prostate cancer continues to be the most diagnosed cancer in U.S. men, accounts for almost 1/3 of the cases, and at the current rates of diagnosis it’s still about 1 man in 6 in his lifetime in the United States. We expect about 220,000 new cases this year. And unfortunately it continues to be a very common cause of death from pros – from cancer in the United States, number two only to lung, and if we could eliminate smoking that would probably move into first place. And this will work out to about 32,000 men who will die of prostate cancer this year. So we have a very commonly diagnosed cancer which unfortunately also results in death for some men who are found to have it.
You can see the effects of PSA screening as we look at prostate cancer incidents, so you can see that before there was PSA the rates of diagnosis of prostate cancer were largely done at the time of TORP or on digital rectal exam, and when PSA emerged in the middle ‘90s there was a huge spike in the rate with which we diagnose this disease. I found it somewhat amusing when I heard Rocky say, you know, if we do more colonoscopies we’ll find a lot more cancers, well look we did a lot more PSA tests and we found a lot more cancers and I’m not sure it’s all good. You can see that we eliminated a lot of cases that were sort of in the background, but since PSA has been around we’ve never retreated back to the rates with which we had diagnosed prostate cancer in the past.
The good news is that the death rate from prostate cancer, as is the case with many solid tumors, has declined. And this is in the face of an at risk population that’s aging, so the Baby Boomers are now just coming into the age where prostate cancer will be diagnosed and we expect that if all things being equal the death rate in fact should be going up, not going down. But that’s not what we’ve been seeing, in fact we’ve seen a decline in the death rate from prostate cancer since PSA screening has begun.
Well isn’t this all very good news? Yes, it is good news and when I was a resident before PSA came around roughly ¼ of all men to came into the hospital with prostate cancer had metastatic and often symptomatic disease. That now accounts for less than 2% of all the prostate cancers that we see. So in the pre-PSA era only less than half of our patients came in with what would be considered to be clinically localized and curable disease, and more than half had advanced or locally advanced disease. Today over 85% of patients diagnosed with prostate cancer have clinically localized prostate cancer, and this we would argue is very good evidence of the effectiveness of screening for prostate cancer. Unfortunately it brings with it a lot of luggage. You can see that the, this is borne out and you look at population based studies, this is something known as the capture database which is a combination of both academic and community practices looking at the type of cancer that walks into the door and over this period of time to 2002 high risk disease has decreased significantly, and at the same time there has been an increase in what we consider to be low risk prostate cancer.
Well, society is beginning to wake up to the fact that so many men have the diagnosis of prostate cancer and in fact earlier this year on the wire the American Cancer Society made this declaration that perhaps we should stop offering our patients PSA testing or perhaps let our patients decide whether they in fact want to be screened for prostate cancer. And we’re even seeing things like this, which just was published, the Invasion of the Prostate Snatchers. Isn’t that a great title? No more unnecessary biopsies, radical treatments or loss of sexual intimacy, and this was written by a team of both a, a, a long term prostate cancer survivor who has had no real definitive therapy, he probably has disease that is you know going to be autopsied like, and then a physician. But really what they are trying to point out is that we as urologists and as people concerned about prostate cancer have put on blinders and viewed every one of these sort of in the same way, and shouldn’t we in fact be more stratifying in our approaches to this.
Well, the problem really doesn’t begin with urologists, by the time you send a patient to us we are more or less along a path that’s already begun, and that is that the patient has some reason to be in our office, i.e. either there’s been an abnormal exam or more likely an abnormal PSA test. And so really this is a question for primary care doctors like you all, which is that should we be screening for prostate cancer?
Well what are the downsides of screening for this disease? The first is, and this remains true, most prostate cancers actually are remarkably latent, so next time you walk into a nursing home and see a bunch of men that are 80 or 90 years old recognize that almost all of them have histologic prostate cancer but don’t need to know it, and in fact we never would treat that. The very test we use to diagnose prostate cancer, PSA, is elevated artificially in about 2/3 of the men who have an abnormal PSA. So even though I’m at the end of a long funnel, only about 40% of the biopsies I perform are actually positive for prostate cancer, meaning I’m doing a lot of biopsies in people who don’t have the disease.
And there has not yet been consistent definitive level one evidence that prostate cancer screening reduces prostate cancer morbidity and mortality. And the key in that sentence is the world consistent. Prostate cancer treatments are clearly harmful, we would love it if we didn’t bring men to their knees with erectile dysfunction and loss of, of continence. Screening clearly is morbid, biopsy is nothing anybody wants, and it leads to more studies, and this is very costly if you assume one man in the United States needs to be treated for – 1 out of 6 needs to be treated for prostate cancer in his lifetime. Well why would we in the face of that ever screen for the disease? Well you want to screen for things that are common, prostate cancer is common, and you want to screen for things that if you don’t detect them in an adequate period of time the patient might die, and prostate cancer as I pointed out is the second leading cause of death from cancer in the U.S. And it’s still true unfortunately that effective treatment is limited to localized disease. So men with metastatic prostate cancer, if they are young and they are healthy they will die of prostate cancer, and that unfortunately is still true today.
PSA is effective, it’s not perfect, but clearly it’s the best tumor marker far and away of any tumor marker that exists is the PSA test. So yes, it picks up things other than prostate cancer, but it is actually the rate cancer that you can miss by having a PSA test. And it very much picks up the disease we want to pickup that is localized and early disease when it’s curable. And the – finally when I argue about whether we should screen or not I ask the people I’m arguing with have you ever had a patient die of prostate cancer? I mean it is awful because they don’t die right away, it’s a very long and painful process. And so if you could avoid that fate, even if you have to put yourself at risk for some of the side effects of our treatment, I think it’s – it has some merit.
Does anybody know who this is?
Will Rogers.
Very good, you know when I ask the residents this question, when I give this talk to residents, they have no idea. So you are showing your age. So Will Rogers was famous for his dislike of people from California when he said when the Okies left Oklahoma and moved to California they raised the average intelligent level of both states. And this is what we refer to in medicine as stage migration, and this has clearly been evident in prostate cancer. So if you look at situation 1 here, that is before we had PSA screening patients would present usually with somewhat advanced disease. We would intervene, not very effectively, and they would go on to die of their disease, and their survival time was maybe 10 or 15 years. Now with PSA screening we pickup their disease, assume we still don’t have effective therapies, which isn’t in fact true, it looks like they are surviving much longer. But all we’ve really done is labeled that patient with prostate cancer at a point in their life where they are going to live longer and then eventually die of the disease. So clear evidence of lead time bias. And we have to recognize that the improvements we’ve seen in prostate cancer management are somewhat overlaid with this problem of knowing that we are picking up disease much earlier than we used to.
This is a little bit busy but I think it’s worthwhile walking through it. If you look at patient 3 here, who has an advanced, or has a lethal form of prostate cancer, screening is introduced by these two screening episodes would fail him. In other words, his disease would go from microscopic to metastatic so quickly that the only screening regimen would have to likely be weekly to pickup his prostate cancer. And on the other end of the spectrum, patient number 1 is never destined to die of prostate cancer, in fact doesn’t have a prostate cancer you actually need to diagnose, so screening of that patient you might pickup as disease but that’s not going to change its natural history. And patient 2 is really the world that I live in, which is these are patients we believe when we screen them in fact the introduction of effective therapy changes the natural history. That is that is somebody who otherwise would have gone on to die of prostate cancer and by introducing effective therapy we in fact allowed them to die of another cause.
Well, the question about screening has been very difficult to answer because in the United States screening is done widely, but in Europe PSA screening in particular was not done at all. And so a, several Europeans from a number of countries, 8 different countries in Europe got together and decided to sort of pool their resources and do the definitive screening study, which was published in 2009 in the New England Journal of Medicine known as the European Randomized Study of Screening for Prostate Cancer. And the primary end point was a good point, that is would we have any impact on prostate cancer mortality, not prostate cancer progression or prostate cancer recurrence, but mortality. And that is comparing a screened population to a non-screened population. The study started in 1991 and all patients were enrolled by 2003 in 8 different European centers which happened to also be in 8 different European cities. They included the at risk population, men 50 to 74, and the screening interval was really not quite as rigorous as it’s applied in the United States with annual tests, but it was applied every 4 years or every 2 years depending on the country one lived in. And then biopsies were recommended for anybody who had PSA’s over 3, again a slightly lower threshold than what we would apply in the United States.
This was a huge study, so the screened and control arms are not exactly the same because in Finland there was a lot of belief that screening was bad so they randomized 1 ½ to 1, but be that as it may the screened arm was 72,000 and the control arm was nearly 90,000. There were a large number of screening tests done, over 126,000, and 20,000 of these patients, about 16%, remarkably close actually to the rates with which we find prostate cancer in the United States, were positive.
And European mean actually were pretty compliant with going onto the next step, that is having a biopsy, something very different than you’ll see in the study I’ll talk about from the United States. So 85% of European men who had an abnormal screening actually underwent a biopsy to determine in fact if they had prostate cancer. They found 4,000 cancers, the predictive value of a biopsy is about 25%, which is pretty close to what we see in general urologic practice, if you simply biopsy people who walk in the door at risk. And the follow-up of this study median was 9 years, a point I’ll return to. This is simply the schematic.
What did they find? Well, not surprisingly, if you screen for prostate cancer you’ll find it, in fact you'll find it at a rate that’s almost twice as common as if you don’t screen for it. So they found it, the prostate cancer detection rate in that population of 8.2% compared to 4.8 in men who simply showed up with usually more advanced disease. And the number of deaths that occurred also was lower in the screened arm, 214 to 326. It’s amazing though that you have to start with about 90,000 men and you only have 326 at the end, it speaks to the challenge that we face in managing this disease. And if you look at it in the attempt to screen analysis, 20% fewer men died of prostate cancer if they underwent screening, and if in fact they were compliant with the screening that went up to 27%, and this difference was in fact significant.
So what’s the absolute risk reduction? That is if you are sitting across from the patient and you say well, how many people do I have to screen to actually show a difference? It turns out that you have to, you can, you can save the lives of 7 men if you screen 10,000. Which mean the number needed to screen is about 1,400. And if you were to look at who needs to be treated to prevent one prostate cancer death, and this is the figure that’s really been picked up quite a bit in the popular press, in this study you had to actually screen and treat 48 men to save one man’s life from death from prostate cancer.
How does this compare to mammography? I’m not a breast cancer specialist by any means so I simply went to the literature, but here in one study the number needed to screen over 5 years in women 50 to 59 is 2,400, very similar to what we seen with prostate cancer. So the complaint that prostate cancer screens unnecessarily is not so different than what we see with mammography. And frankly, it’s not so different from what the data you just saw for colonoscopy.
I think the other important element of this issue of one has to be – one is safe for 48 treatment, that is a time dependent variable. So again looking at the breast cancer literature, if women have high risk of developing breast cancer given a family history and they decide to undergo prophylactic mastectomy as the way to manage the high likelihood they will develop invasive breast cancer, you can see that death from breast cancer at 10 years you would have to, you would have to do bilateral mastectomies in 44.8, but as you move farther out, now at 15 years the number that you would need to treat drops to 25. So really when you hear that number 1 in 48, that’s at 9 years. When I see men with prostate cancer I tell them look at, the reason I’m going to operate on you today is not because you are going to die in the next 10 years, it’s because I want you to be alive 20 and 30 years from now. And in fact if you are not going to be alive for other reasons in 20 or 30 years from now, we should be very circumspect about whether in fact you should be treated.
Here are the Kaplan/Meyer type analyses, it’s actually not a Kaplan/Meyer, it’s a different statistic, but you can see that, that the separation of these two curves in this study at 9 years was pretty trivial, but as you move farther out you can see the, the excess number of deaths increased in the control arm compared to the screening arm.
One of the strengths of this study is that there was no heterogeneity by center, so each country had the exactly the same result roughly, and that was about a 16 to 26% reduction in prostate cancer mortality, which means that this wasn’t driven just by the Netherlands or just by France, this was driven by the com- the combination of all the centers.
Okay, well that’s great for the Europeans, we live here in the United States, and in the United States prostate cancer screening and particularly PSA screening is widely conducted. In this study in 2003 in JAMA at every age group PSA screening was more common than colonoscopy, for which there is actually good evidence that in fact you should recommend colonoscopy to your patients. So we live in a world where PSA is already out there and widely done. And if you ask practicing clinicians, and I’m sorry it’s small but I believe it’s in your hand-out, you can see that most practicing clinicians in fact would recommend that screening be offered to men over the age of 50, and only a minority feel that it shouldn’t be offered at all to patients who are over the age of 50. So our general practice, and this is now you know family doctors and internal medicine doctors think that this is a good thing to do.
Well at the very same issue of New England Journal of Medicine where the European study was published, this study was published, which asks the same general question in an American population. And they took advantage of the prostate arm of the so-called PLCO study, which is a screening study looking at an end point very similar, that is does screening for prostate cancer reduce mortality in a non-screened, that is within the auspices of the PLCO study as compared to a screened arm within the auspices of the PLCO study? This was in the same time period, ’90/’93 to 2001 at 10 US sites. It’s about half the size of the European study, same general age groups. The screening here was more an American flavor, that is annual digital rectal exam and annual PSAs. Very much unlike European study though, if anybody screened positive they were sort of sent loose into the usual care of their community. These are the PLCO screening sites. It turns out the University of Pittsburgh where we are here was one of the sites. And not unlike the European study you can see that if you screen for prostate cancer you’ll find it more commonly than if you don’t screen for it, and that’s clearly shown here over time. But very different than the European study, in America screening for prostate cancer over 7 years has no impact at all on prostate cancer mortality.
Well what are some of the problems with the PLCO study and why have I said very frequently in public I can’t believe this actually got published in the New England Journal of Medicine? The first is that because PSA screening is so widely done in the population in the 3 years up to going into the study roughly a third of men had already undergone PSA screening. That immediately removed from the population everybody who has a bad prostate gland, or the third of men who had screening, if you were destined to have cancer, so you have healthier men in the screening population, healthier prostates that is.
The second problem, which is the major problem is that the control arm, the arm that wasn’t supposed to be screening in fact was screened at very high rates. So within the first year these guys just went across the street to their family doctor and said look, I got randomized to the arm in the PLCO where they are not going to do a PSA but my neighbor got prostate cancer, can you just draw PSA on me because I’m a little nervous about this? And by the sixth year of the study half of the patients who weren’t supposed to be screened in fact were screened. The final problem with the study is that these patients told you have something wrong, only about 40% of them actually proceeded to find out what their problem was. So if you are going to – nobody thinks that doing a digital rectal exam and doing a blood test is going to save anybody’s life from prostate cancer, you actually have to intervene on that information. And so the follow-up is really pretty weak in this study, very much unlike the European study. And then they are only looking at data out 7 years, I really think none of us would have expected any difference at 7 years because you are talking about a slow growing cancer. This isn’t like pancreatic cancer or glioma where you are going to get your answer quickly, this is one you have to look out 15 to 20 years to see what the differences are. And I just point out to you that at 7 years in the European study there was no difference at all between the screened arm and the control arm, so the PLCO study shows us the correct data, but the follow-up is simply too short as supported by the European study.
And I think I’ve made these points significantly, so is there evidence that we should do prostate cancer screening? Yes. In one study there is level 1 evidence that screening reduces the risk of dying of prostate cancer by 20%, and if you are compliant with your biopsy it’s 27%. However we have to add that this is in men age 55 to 69 who happen to live in Europe, so those of you that want to emigrate to Europe you should go get screened. That comes at I think a considerable risk of potentially unnecessary treatment.
The other answer to the question would be no, actually in fact in the United States there is no reduction in death from prostate cancer in a 7 year follow-up period of time, in a more intensively screened group compared to a less intensively screened group. So for your patients I think the honest answer is if I’ve ever done a PSA test for you, what’s the likelihood that PSA tests is going to do today in terms of saving your life from death from prostate cancer in the next 7 years, it’s you have to say there is no evidence this is going to save your life in the next 7 years.
Well what should we do with our patients? The American Urologic Association of which I’m a member took this information and said aha, we should be doing exactly what we said we should be doing, and that is in fact we should be screening even starting at the age of 40 because the people that really have a lot to lose to prostate cancer are the young men, so this morning I operated on a 44 year old, and I felt very good about it because I know untreated he was going to die of prostate cancer, because he’s so young, he’s got to live for another 40 years. On the other end of the spectrum, the American Academy of Family Physicians feels that there is really insufficient evidence on which to recommend for or against routine screening for prostate cancer using this PSA test and a digital rectal exam. So here we are sort of stuck between the two polls.
I just want to tell you that there are some things you need to remember about PSA testing, that is that the idea that the number 4 and above is wrong, and the number of 4 and below is okay, you need to forget that. That’s not true. So in this study that looked at the use of Finasteride or Proscar, excuse me, I didn’t say that, Finasteride in chemo prevention at the end of the study about 3,000 men underwent a biopsy. They didn’t have anything else to suggest they needed it, but it was the study design. And what they found was that if you had very low PSAs you still had a reasonably high chance of being found to have prostate cancer. And if you look at the cohort with the PSA from 3.1 to 4, almost 27% of those patients if you simply stuck a needle into their prostate gland you’d come across prostate cancer. So you can’t believe that if somebody’s PSA is 2 there is no chance they have prostate cancer. In fact in this study if your PSA was 2, you had about a 25% chance of having prostate cancer.
The other thing to recognize is that young men should have low PSAs and older men can have higher PSAs, and the race of your patient actually something to say about what would be considered normal or abnormal, and this is in your hand-out. Asian men, African-American men and Caucasian men all have different age specific PSA ranges.
I’m asked regularly by defense attorneys mostly to try to defend medical doctors who have been, are being sued because they didn’t diagnose a prostate cancer. So what are some of what I think are avoidable pitfalls? If you have a discussion with your patient about whether or not you should screen for prostate cancer and you actually document that in a medical record, I don’t see that you are – there is any problem. Because if you say and the patient agrees that they are not going to be screened for prostate cancer, we can all bring out all kinds of data that would indicate that in fact that’s appropriate. To not have a discussion puts you at some liability.
One that I’ve seen repeatedly is that people just don’t like doing digital rectal exams. And I don’t like doing them either, but I have to, right? So you can’t just rely on a PSA test because some prostate cancers in particular the really bad ones stop making PSA, and you can only pick them up by actually feeling the exam – the gland.
And then obviously things like an abnormal test just gets dropped on the end of the lab slip and you don’t pay attention to it, or somebody has a change in their PSA that somebody in hindsight would say boy, you should have done something about that. Also deciding to do a PSA test every 5th year or every 6th year, unless you can support that you are really on pretty shaky ground. And I think that the uncertainty about screening really should not allow you to be silent or to do an incomplete evaluation. So if in fact you are going to screen for prostate cancer do it correctly, annual PSA, digital rectal exam, age 50 until that patient has a less than a 10 year life expectancy, earlier if they have family history or African-American race.
Well what about those of us that treat prostate cancer? And if you pose it to those clinicians, you have a young man, he’s healthy and he has low risk prostate cancer what would you do? And you can see that the radiation oncologists have all the things they like to do, brachytherapy, external beam, 3-D conformal, surgeons we would say take out his prostate gland, but unfortunately only a fraction of physicians who manage prostate cancer are actively in involved in simply observing men with prostate cancer, and I think this needs to change. And let me give you some evidence on why.
So my colleague, Laurie Klotz, who lives in Toronto, and I’m quick to point out this is a Canadian study where healthcare delivery is very different than it is in the United States. This study where he took 450 men and he put them on active surveillance, now let’s be clear about the language here. What active surveillance means is that you are still going to potentially intervene on that, on behalf of that patient with curative intent when their disease progresses. That’s different than watchful waiting. Watchful waiting says no matter what happens with your prostate gland the only intervention we are going to apply is going to be palliative, watchful waiting is generally done in the 80 year old men, active surveillance in men who still have some risk of death from prostate cancer.
So this Canadian cohort, he followed this patients a median of 6.8 years, and these were men that we would expect would be appropriate for an active surveillance protocol, they were old, 70 median age. And interestingly at 10 years of follow-up the proba – the overall survival of this population was 68%. And that pretty much approximates a death curve, right, 70 year old men, 10 years later 80 year olds, you expect about 40% of them are going to die. But quite interestingly the cancer specific survival at 5 and 10 years was 99 and 97%, so very, very few of these men selected for active surveillance actually died of prostate cancer.
And if you look at the mortality, all cause mortality versus prostate cancer specific mortality, the hazard ratio was 18. So when I see a 70 year old man who has low risk prostate cancer and he says well if I don’t get treated what’s the likelihood I’ll die of prostate cancer? I say it’s about 20 times greater you are going to die of something else. And if you stratify by age and you look at men over, over the age of 70 the hazard ratio for death from another cause is 33 to 1. And if you are under that age, it’s now something where we begin to get a little nervous, it’s only about a hazard ratio of 8.
What’s the likelihood you actually could stay on surveillance? Well if you die you are obviously not going to stay on surveillance, so most of this curve is just driven by death from another cause. Remember at 68, at 10 years 68% of the patients had died, so only 6% of the patients at 10 years had actually undergone some intervention. Why? Well most it was due to changes in PSA kinetics, and this is a very controversial area in our field so I can’t say that there is consensus about this.
One of the criticisms of the Klotz study and active surveillance in general is that if you watch a patient long enough and then decide to intervene your intervention is not going to be nearly as effective as it would have been had you applied it earlier. And you kind of want to say da, of course. I mean if I would have treated this patient when he walked in the door I would have cured him. And if I watch him, the likelihood of cure goes down, but that’s the risk you explain to the patient. The truth is that many of these men never need, will never need to be treated so they can avoid it completely. But if I were to show you these data for either radiation or surgery in newly diagnosed patients, the results are going to look much better than they would look in this population where you sort of selected for the progressive diseases, progressive tumors.
This has been supported, his observations have been supported by what now is considered sort of a landmark and somewhat historic study where men in Scandinavia were randomized to either get watchful waiting, that is no treatment at all and only androgen deprivation at time of progression or radical prostatectomy. And this is a very interesting set of curves that were updated 2 years ago in GNCI. The overall mortality for men who underwent watchful waiting over the age of 65 was identical to the men who underwent surgery over the age of 65, and the only people that really seemed to have a lower overall mortality was if they had surgery and they were under the age of 65. And the congress of this, supporting it is that the only population that had an excess death rate from prostate cancer were in young men who in fact did not get treatment. So based on data like these, we really think that we are moving into the, the age where we are going to be very selective about who we should recommend treatment for prostate cancer. That doesn’t mean we don’t manage their disease. You can’t cure diabetes usually, but you manage it, right? Well you can’t necessarily cure prostate cancer, but if you are not going to die of the disease, you just manage it, you observe it and you only intervene when it’s necessary.
So what are my conclusions? The lack of consensus on prostate cancer screening does not equate to silence on the issue, and I think it’s important since you all are really on the front line, again by the time they get to me, I mean we are sort of obligated to investigate. You need to understand what the nuances of it – of this issue are. I think there are clear results from our widespread screening and that is that there is overtreatment of prostate cancer, and I think we are going to need to be increasingly sophisticated about who we apply treatment to. But on the good side there has clearly been a decline in late stage disease, and we expect that in fact the death rate from prostate cancer will continue to go down even in the time when the at risk population is growing older.
And finally, a prostate cancer diagnosis no longer should be monosynaptic, I’ve got to treat you, right? You need to have a discussion with the patient, if it’s high risk disease yes you need to be treated, but for low risk disease in an older man I think that often the best way to manage that patient is to sit him down, tell him look, prostate cancer has the wrong last name for what we’ve found in you. It’s something in your prostate that we need to take care of, but it’s nothing that’s really going to harm you. And I think that’s my last slide.
Before I thank you I also want to say, and I know this is somewhat impersonal, I think I got the opportunity to take care of many of your patients over the last 11 years and it’s been really an honor. Thank you.
Dr. Joel Nelson is the Frederic N. Schwentker Professor and chairman of the Department of Urology, University of Pittsburgh School of Medicine. He also serves as the co-director of the Prostate and Urologic Cancer Center at the University of Pittsburgh Cancer Institute. Dr. Nelson earned his ...