Surgical Treatment For Prostate Cancer Webcast May 6, 2010 John W. Davis, M.D., F.A.C.S. Mike Whyte. Mike s Story

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Surgical Treatment For Prostate Cancer Webcast May 6, 2010 John W. Davis, M.D., F.A.C.S. Mike Whyte Please remember the opinions expressed on Patient Power are not necessarily the views of M. D. Anderson Cancer Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. Mike s Story Surgery is one of the primary treatment options for prostate cancer. Coming up a leading urologist from M. D. Anderson Cancer Center will discuss the details of minimally invasive surgery and open prostatectomy and who surgery is right for. It's all next on Patient Power. Hello and welcome to Patient Power sponsored by M. D. Anderson Cancer Center. I'm Andrew Schorr. Well, I know men my age, I'm 59, we think about prostate cancer. My father developed prostate cancer, had surgery, he did live a long time, to 92, but certainly it's on my radar and it probably is on yours too. There are over 200,000 men a year diagnosed with prostate cancer. Now, there's been all this swirling about, should we be screened with a PSA test and what age, and was does it mean, but for some people that test does come back elevated, let's say, at a routine physical where it might happen, and then you have biopsies and they're positive. Then the question is what to do. I want to introduce you to Mike Whyte, who is 57 years old. Normally his home is in Cypress, Texas, but he does travel around in his business in the refining field, and he joins us today from Atlanta, where he's on business. Mike, you had surgery just about seven months ago for prostate cancer, but if we go back to the previous summer there was that exam where the PSA test was elevated. That's got to be scary. Well, it was. It was very scary. Since I'd never experienced anything like this before, it was a surprise. And your dad too had dealt with prostate cancer. Correct.

So it brings up a lot for anybody in that situation. You know, a lot of times someone has a diagnosis of cancer and it's like a five alarm fire and you want to deal with it right away. Typically prostate cancer is slow growing. You took time to do research. Right. I did. There were so many options available I just wanted to make the right decision, something that would give me a good quality of life and get rid of the cancer. Now, for you was question was having treatment, and you had, as we'll learn a little more from your doctor in just a minute, the biopsies came back, five of them positive, some with low-grade cells but at least one with intermediate grade, so the question was you probably needed treatment was the thinking, I guess. You looked into radiation but then chose surgery. How come? I wanted to be sure that I got rid of the cancer. I just felt like the radiation, there was that small chance that it could come back again, and I just wanted to get rid of it. Now, we're going to do another program coming up where we'll talk with one of the leading radiation oncologists in the world for prostate cancer, and we'll understand that. Today we're going to talk about surgery. So you had the surgery in the fall of 2009, robotic surgery, which we'll learn about. How did it work out? Recovery, side effects, tell us how it went and how you're doing. Well, the surgery was surprisingly a relatively easy recovery. I was in the hospital for just one night, experienced some minor discomfort for a few days after but for the most part it was a lot easier than I expected. Now, men worry about incontinence, erectile dysfunction. How has it worked out? I have been fortunate that I have not experienced any of those side effects. There was some minor incontinence for maybe a couple weeks after the surgery, but all that's since gone away and there have been no other problems. 2

Decision-Making Tools Well, let's meet your doctor, that's Dr. John Davis. Dr. Davis is assistant professor in the department of urology at M. D. Anderson Cancer Center. He's been on Patient Power before. He's a veteran with us, but he's also been very involved in prostate cancer surgery for a number of years. He's done over a thousand of these robotic prostate cancer surgeries. Dr. Davis, thanks for joining us. So Mike's story is a happy one, I guess, at this point, but there's always the question, who needs surgery, and later we'll talk about which approach. How do you decide with a patient when to go forward? Where are we now with decision-making tools? Hello, Andrew. Good to be back. That question of course is kind of coupled in with the screening debate because, you know, screening leads to often a man like Mike who is in an office who feels fine and has this blood test abnormality that leads to a biopsy and then all of a sudden he's told he has a cancer diagnosis and has to do a crash course on all these options available. What we've learned I think through some large data sets over the years is that we know that PSA screening detects a lot of tumors. The detection rate certainly goes up when you use that, but it's not an entirely satisfying test because it kind of brings out three different categories of patients. One are patients for whom the cancer diagnosis is purely low grade and only seen in maybe one or two biopsies, and if you treat these the patients will do well but they tend to have tumors that are very similar to something you would see if you did an autopsy exam on someone in their 90s of something else. That's the idea that most men, if you live long enough you'll die with prostate cancer but not from it, correct? Correct. So PSA definitely picks up on those, sometimes by accident. Some of those men probably just have benign enlargement that elevated the test. Then Mr. Whyte is more of that ideal finding where we find somebody with intermediate-risk disease, and in fact his grade was one notch higher when we did the surgery. It was Gleason 4 plus 3 versus being 3 plus 4 on the biopsy, so we were retrospectively reassured that his surgery was beneficial to his long term well-being. On the other hand we also see a segment of patients for whom the PSA screening is actually too late, meaning they have high-grade disease that has advanced to some degree and there was virtually minimal alarm bells going off with the PSA testing. 3

So it can err on both sides, but Mr. Whyte's case is the happy medium where it was early enough to be successful and perhaps necessary. So I think that kind of is the outline of how we think of patients of having low-risk disease, intermediate-risk disease or high-risk disease. The low-risk patients in many cases can consider surveillance or surgery. I must admit some men with a family history like Mr. Whyte's are more prone to want to get it taken care of just in case, so to speak, and active surveillance is not without its own set of challenges in terms of monitoring, which we can go over. Most men with intermediate-risk disease with good survival should consider one of the treatments, and then there's another discussion that goes into how to pick one. And then high-risk patients is a persistent clinical challenge because a good fraction of those patients may have a relapse, so those are the people we target for novel treatment agents, clinical trials and that kind of thing to try and improve. Surgery Let's see where we are with surgery now. Now, we mentioned the robot, and you're well familiar with that over a number of years. Sure. And any man who looks into prostate cancer treatment now hears about it. And then there have been open procedures for a number of years, and I know you've done many of those. How do you decide what are situations where one over the other, or is it really the skill of the surgeon? Just help orient us about what's important. Well, the background of this is to mean to ask why would you want to improve any intervention in cancer treatment. It's usually related to can you make it cure any better or can you deliver it any cheaper or quicker or can you reduce some of the side effects. And if a man looking at open surgery say 20 or 30 years ago was signing a consent you would be faced with a huge paragraph full of potential complications. Erectile dysfunction was almost true in all cases until surgeons learned how to preserve nerve bundles. Incontinence was common, bleeding in transfusion, on and on and on. So the operation although it had some potential for curing cancer also had a lot of side effects. Now, so one approach has been to just keep doing the surgery more and more often and to study anatomy carefully, and there's a handful of surgeons in their late 50s who spent their whole career trying to teach and perfect this open operation, but it's still fundamentally changed by being a difficult location to operate. It's 4

deep in the pelvis. It's difficult to light and see without magnifying glasses, and it's an area of the anatomy that's just prone for sort of a slow and steady bleeding that of course is more work to manage and can be distracting. So the initial minimally invasive approaches all over various types of surgery always through the camera view and the gas infusion use could decrease bleeding, increase visualization, and it took us some ten years of laparoscopic surgery before surgeons would tackle a prostatectomy because of the complex reconstruction required. And it really was a handful of European centers that showed that you could do a laparoscopic prostatectomy with good results. And once the robot came in the early part of the last decade that basically answered all of the concerns of the laparoscopic approach, meaning now all of a sudden you could see the patient in three dimensions, and the instruments could rotate like a human wrist such that suturing and reconstruction and access was all basically solved. So that's kind of the history of where we led to it. You have an operation that needs improvement and a series of steps to get us to that point. So most of the time that is the approach you take. There is a learning curve associated with it, and certainly your hospital has to purchase and maintain the equipment, and so it's slowly become over, I'd say, from 2004 to now it's probably about 70 to 80 percent of all prostatectomies are done with a robot, at least in the United States. Now, the other question, and you mentioned along the way, nerve sparing. Yes. So it's great Mike is doing so well, but that's a fear of any man who goes under the knife, if you will, is will my urinary continence be preserved and my sex life, basically. So where are we now at M. D. Anderson as far as your ability to help men preserve that? Well, let's talk about erectile dysfunction first. There's a number of factors that go into that. That's actually the hardest topic to discuss and to get an accurate description of. First of all, the PSA screening, since it's been ongoing for so many years has led to our current situation where we're discovering tumors much earlier in their natural process so they tend to be smaller and more likely contained. We've also just had a number of years of comparing our biopsy numbers to our prostatectomy numbers and we've really learned that most men with low- to 5

intermediate-risk disease can have both nerve bundles spared safely, and actually a good percentage of high-grade men can actually have one and sometimes even more of the other side spared as well. So screening has led to nerve sparing being safe from a cancer perspective, and that's obviously the first requirement and then obviously there's detailed study of the anatomy. The robot clearly takes away a lot of the bleeding distraction and gives you magnification, so we've learned very nicely how to spare nerve bundles right down to the edge of the capsule of the prostate without getting into it and leaving tumor behind, and this has allowed for improved success rates. Now, that being said, surgeon experience in sparing two nerve bundles are two important things but there are others. Obviously a patient's age is highly important in terms of how well erections will recover. Also their medical background, their baseline sexual function. People who have smoking-related and vascular-related side effects tend to have more risk for these problems. So when we look at the ideal patient we can push some 80 and 90 percent success rates. However, globally if you look at the entire population that has this surgery there's clearly an erectile dysfunction side effect based on all these potential risks. Urinary incontinence? Now, that part is more of a good news story. Again because the screening gives us smaller tumors we've learned how to really take dissection right down to the urinary muscles, very close to the prostate and preserving all the, basically the muscles that wrap around the urethra that give you control and then to do a good reconstructive job so that it doesn't scar. So we can really tell patients today that most patients recover the vast majority of their urinary control in their first three months, and if we study people at one year with surveys that they fill out themselves their average scores are basically equal to their preoperative scores. Certainly some patients may have some minor stress incontinence in one year, but the sort of devastating, permanent incontinence is now approaching something close to one percent. And the other good news of that is that we found essentially the same overall recovery rate even for men in their 70s. There are some men in their 70s or 80s who have high-grade disease and maybe are not good candidates for radiation but occasionally need the same surgery, and we found that actually their age does not preclude them from expecting good urinary control. All right. We've got so much more to talk about and a lot related to decision-making and hour to proceed. Do you have surgery? Mike worked through decision-making on whether he was choosing surgery over radiation and how a 6

multidisciplinary team can help you and make recommendations, and they have that at M. D. Anderson. So we'll hear more about that when we continue our Patient Power discussion right after this. Welcome back to Patient Power. We're talking primarily about surgical approaches for prostate cancer, but we're also going to cover how do you get though that point of deciding is surgery right for you. Now we were talking about robotic surgery, nerve-sparing approaches, and of course the traditional way of doing prostate surgery, this is what my dad had years ago, was open, and maybe, Mike, that's probably what your dad had for sure, right? Okay. So that happens. Tell us, Dr. Davis, are there some times when that's the preferred approach for certain populations and why. Again, I think some surgeons who are excellent at open surgery can continue to do so. The tough part about analyzing these data is it's hard to separate the technique from the experience of the surgeon. So if someone is going to be robot case number five versus open case number 1005, then you're probably going to get a better result with the open approach. But once numbers have increased we're starting to see some publications of what robotic comparisons look like across large numbers of surgeons. And again, these are still learning curve sort of cases potentially, but essentially these population studies are showing us that hospital stays are shorter, blood loss is less, complications are less, urinary scarring is less. On the other hand it's interesting that we have not seen dramatic difference in impotency and incontinence, and again this is probably more experience related than technique related. At M. D. Anderson we've at least been able to look pathology results and show that the robotic positive margin rate is just a few notches lower than open, certainly not worse. So we've been able to introduce the new technology safely, so to speak. And is there any population where you'd say, well, we really should do an open approach? Something about that patient where it would be indicated? Not strictly across the board. I think surgeons who might be in the earlier experience with robotics may want to stay away from high-grade or more difficult cases early on, maybe related to patient's weight or something like that. Okay. But most surgeons with time can adapt to all these situations, and they'll prefer the robotic environment once they're comfortable. 7

Now, on so many of our programs, and I know it's kind of basic at M. D. Anderson, you have what's called a multidisciplinary approach. So help us understand how that works. So, Mike, when you went to M. D. Anderson did you meet with more than one doctor? No. Dr. Davis was the only doctor I met with this there. I had seen another surgeon prior to going to M. D. Anderson. How does it go, Dr. Davis, when there's really more to talk about or whether radiation could come into play or even medical oncology? Tell us about that. Sure. We have a staff in our clinic that their full-time job is arranging new appointments, and so they put the patients who call through a series, you know, a personal interview to try to understand their situation and their needs, and also they try to assemble their medical records and biopsies so we can review all that. In general if the patient says, I have prostate cancer and I don't know what to do about it, then by default they will go to one of these multidisciplinary clinics and see a surgeon and a radiation oncologist. Now, if a patient has already heard about a particular doctor they want to see or they know they want a certain modality then they'll get assigned to a clinic that does that full-time. Now, that being said, sometimes I see a patient who got referred to me directly and they still have questions about radiation oncology, so even after the fact we can schedule a second appointment with a radiation oncologist. And vice versa. Some people start out with the radiation department and maybe are found to not be good candidates for that and so then they reassign them over to talk to a surgeon. So we try to share and get people to as comfortable a point of knowledge and research as they want to be to make the decision that's best for them. And, Mike, you had decided on surgery when you saw Dr. Davis. Yes, I did. I met with radiologists and other surgeons prior to meeting Dr. Davis and pretty much had my mind made up. Active Surveillance Now, what about this term "active surveillance," Dr. Davis. That's been out there for a years. I know earlier over many decades we had this term "watchful waiting." Active surveillance, some men may have results where it says they have low-risk prostate cancer and you mentioned it's not without certain intervention and maybe 8

you can describe that. I know you have PSA tests and biopsies and there's sort of a schedule for that. What does that active surveillance mean, and in your opinion who might it be right for? Again, I've seen some recent data that confirms what we've sort of suspected all along. If a man has pure low-grade cancer, not just on a biopsy but on the radical prostatectomy specimen, their like 15-year risk of dying of prostate cancer is one percent or less. So but the tricky part is not every one who has a biopsy Gleason six is really that great because biopsy is just a sampling of the prostate and it can miss certain areas. So we've done a lot of studies looking at biopsy versus prostatectomy findings, and there's about a 15 percent difference there where the prostatectomy is higher grade. So if a man is pure Gleason 6 tumor, especially if it's limited to one or two cores, they can consider active surveillance, and part of our initial challenge is to try to be sure we're not misdiagnosing them, so to speak. So often at our center we will repeat the biopsy, and between the two of them if none of them are showing any elements of middle- or high-grade disease then they can consider surveillance. Then of course we repeat the biopsy in one year. We also measure PSA values at specific intervals and such that over time we can sort of monitor the situation and be sure we haven't missed an area of high-grade disease or that it's not slowly developing into that condition. And there's a group in Canada and some other combined data sets that have looked at approximately 2,000 patients on active surveillance who have about a decade of follow-up, and for patients in this low-risk category who choose this about 70 percent of them are still on surveillance ten years later, whereas 30 percent are found to have a rising PSA pattern or more significant disease on biopsies and then undergo treatment on a delay basis. Risk of Recurrence Now, let's look at the other situation. So Mike has had surgery and hopefully you got it all and he can go on with his life. But what monitoring do you do in someone like Mike to really see is there any risk of the cancer coming back? Well, this is actually the simplest and from my standpoint the beauty of surgery is that even though it may be complicated to do all this surgical intervention and recover, once it's done and you're recovered your future is very clear and easy. Meaning all you have to do is get PSA checks a couple times a year because since we've removed the entire prostate gland we would expect that if he doesn't have any recurrence of his tumor that his PSA should read zero, and that's what's it's reading. It's nice for patients who maybe even don't live in Texas because as long as they go to their primary doctor and get a PSA and it's zero then I'm happy, 9

everybody is happy and there's not a whole lot of other testing to do. Obviously there's other cancer sites where they may require several exams and elaborate imaging to check on them, but a post prostatectomy is one of the easiest tumors to monitor. I have another question related to monitoring. So any of us, and I'm a leukemia survivor and I've been successfully treated by M. D. Anderson, and I believe they saved my life, very grateful. But we worry about the cancer diagnosis, period, even at some other site. Is a man who has been treated for prostate cancer successfully at any higher risk or needs any special monitoring, just anything else related to cancer in their body? We've not been able to find that it links to other cancers. There's some situations, for example a woman may have sort of a link to risk of ovarian and breast cancer and then there are other sort of hormone-based cancers that occur in cancers, but you know prostate cancer is the most common cancer in men, and just because you have or don't have it doesn't mean you can't get number two or number three on the list. I think men should be carefully screened for colon cancer like everyone else and get their skin looked at. Those are the two other cancers that are easiest to screen for in the clinic, but they're not necessarily at higher risk just because they have had prostate cancer. One other question for you, Dr. Davis, so as Mike went through with his own research, or any of us, male or female, looking into prostate cancer, we look for clarity. You want to see clear answers, have this screening test, the screening test result means this or the biopsies mean that. You just said a minute ago did you biopsy the right part, did you hit the right spot or the wrong spot, whatever, in a biopsy. So we wish it was black and white, and in this field of urology with prostate cancer with some patients it is black and white but others it's not. Where are we headed in getting more clarity so that men can make informed decisions? Where are we with that? The number one strategy being looked at is, are there ways we can image actual prostate tumors? Currently if we do an ultrasound or an exam we really can only image really late-stage advanced tumors. We can't really see early tumors such as Mr. Whyte's that was detected by the blood testing. Because if we could actually image the tumors within the prostate gland then the small ones could be monitored. Instead of repeating biopsies you could just take another picture at intervals. And furthermore obviously you could actually target your biopsies right to the tumor instead of having to sample the entire gland. So there are a number of ways of looking at, you know, various ultrasound, MRI, type related technologies, even ultrasound that look at how thick or dense tissues are. Basically all these 10

strategies are being looked at to see if we can improve upon imaging. Because you know there currently is some guesswork that goes into evaluating how significant a man's risk is. Are you optimistic that we can improve upon this? I think so. Often the way he study it is we study this in preoperative patients. You do an image intervention on a patient, somebody who otherwise is going to have a prostatectomy anyway and then you compare the before to the after so you can get kind of a quick answer and know whether or not this technology works or move on to the next. The Future You know, I talk a lot on our programs about the art of medicine. It seems like really the wisdom and the art, and you talked about it even in surgical techniques, as well, Dr. Davis. Mike, for you, how do you feel now about the choices you made, that you had surgery and where you went for surgery? Clearly I think I made the right choice. Where I had the surgery, M. D. Anderson, was just first class from start to finish. I feel happy that I made the decision to have the surgery as opposed to radiation because I know it's gone now and no side effects, so I feel very good about my decisions. Now, it's a process, and you're at a happy point now, but obviously if we go back to July of last year when you were diagnosed, it's a tough time. There are men listening and maybe their loved ones who are back in that place. What would you say to them? Now, every man's situation is different, but is there any guide you'd give them of sort of getting through it knowing hopefully they can get to a better place? Well, I would say, first of all, don't wait too long to get treatment but study your options and feel confident with your doctor and know that it's a very treatable disease. But get it taken care of as soon as possible. Well, Mike Whyte, we wish you all the best. Thank you to joining us on your business trip. Sure. 11

And we really wish you a long and happy life, and it sounds like you did the right thing for you, and we wish you all the best. Thank you very much, Andrew. And, Dr. Davis, so hopefully this can be a story we tell more often. Certainly we'll be doing other programs and we'll talk about the radiation approach, and some people need drug therapy and sometimes it all works together. Sometimes the modalities come together and you all help recommend when that's the case, correct? It is. And I think one of the related things men should learn about is there's been some new screening guidelines from the American Cancer Society that got a lot of press about a month ago because these guidelines really suggested that men should not be automatically screened for prostate cancer because there are potential harms such as the side effects we talked about. And, as we noted, some of these screening events do cause us to diagnose low-grade disease that we almost wish we didn't know about. But sometimes we see cases like Mr. Whyte, more than sometimes, very frequently, and other times it's a high-grade case. So there's a spectrum we see with screening, and I kind of wanted to showcase Mr. Whyte because he well demonstrates that his cancer was necessary, was curable, and he had a good recovery, so it's not inevitable that a man who has treatment for prostate cancer is going to have side effects if he goes to a high-volume center. And this is the same for radiation techniques. A man can have radiation-based therapy and have a good recovery as well. I think the overall compromise is to get screened carefully, and if you're found to have that low-grade variant consider the surveillance and if something else is found then you move on to treatment. Great advice, and I would definitely urge people to, as Mike Whyte did, talk to a team of providers. Talk to one, talk to another, and really begin to do your own research as well to understand your situation. One last question for you, Dr. Davis. It's usually not a five alarm fire. Emotionally it may be, but it's typically slow growing and you have time to get the confidence of how you want to move ahead, correct? Yes. There's some nice studies that have looked at the biopsy findings to the pathology and found that people who are treated any time within a six-month window who have sort of generic, low-to middle-risk disease, there's no difference in their outcome. Maybe you want to hustle it up a little bit if you have high-grade 12

disease, and that's fine. But, no, most men who have intermediate- to low-grade disease, then you have time, like Mr. Whyte did. You don't have to procrastinate it, but it's true, you have plenty of time to research and talk to a number of providers. All right. Well, thank you for being our provider with us today, and thank you for being with us again on Patient Power. Dr. John Davis, urologist at M. D. Anderson Cancer Center. This is what we do, folks, time after time, is connect you with leading experts and inspiring patients like Mike Whyte, and we hope this has brought you some important information as you research what to do about prostate cancer. We'll have other programs, and we have a vast library of earlier programs to help educate you. I'm Andrew Schorr. Remember, knowledge can be the best medicine of all. Thanks for joining us. Please remember the opinions expressed on Patient Power are not necessarily the views of M. D. Anderson Cancer Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. 13