Colon Cancer Screening Webcast April 23, 2008 William Grady, M.D. Introduction

Colon Cancer Screening Webcast April 23, 2008 William Grady, M.D. Please remember the opinions expressed on Patient Power are not necessarily the views of Seattle Cancer Care Alliance, 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. Introduction Hello and thank you for joining us once again on our webcast sponsored by the Seattle Cancer Care Alliance. We do this every two weeks, and I am delighted as a cancer survivor to help you connect with leading experts. Now, usually there are people who are in radiation oncology or medical oncology, but you know there are many other specialties that come into play. One of them is gastroenterology, and if you think about one of the most common cancers it is colon cancer. And unfortunately we have experienced that in my family in two ways. First of all, my mother, Ruth, died at age 77 from colon cancer that became advanced and spread to her liver. And while she did live a fairly long time with that diagnosis, four and a half years, and this was about 20 years ago, it still took her life. Colon cancer screening could have made a big difference. And then my dad was an example of someone who had colon cancer screening and they would find these little precancerous polyps through colonoscopy that we'll talk about today, the importance of it, snip them out and he never developed colon cancer. So you can imagine our family, we really pay attention to that. So that's our topic, colon cancer screening, where new things are happening, new ways of doing it and more coming that can make it really maybe more accessible to people and really it can be lifesaving. I'd like you to meet our special guest who is the medical director of the gastrointestinal cancer program, the prevention program at the Seattle Cancer Care Alliance. He's also an associate member of the Fred Hutchinson Cancer Research Center, and he's the section chief of the division of gastroenterology at the University of Washington. I'm talking about William or Bill Grady. Dr. Grady, thank you for being with us. Thank you. It's a real pleasure and a privilege to have the chance to talk to you today and talk about colon cancer and how we can prevent it. 1

Right. Well, it is not an insignificant problem. Tell us how many people are diagnosed with colon cancer in America these days and how many people die of it. Who Does Colon Cancer Affect? Well, as you mentioned, colon cancer is one of the more common cancers in the United States. It affects about 150,000 people every year, and about 50,000 of those people will die from it. That makes it the third most common cancer that affects men and women in the United States. Overall, it affects about one in 20 people will have colon cancer. And you talked about those colon polyps, and what we know is that polyps are the pre-cancers. And the polyps occur in about one in five to one in four people. So we know colon cancer is very common, and now we have ways for preventing it and that's really what I'd like to talk about today. Right. And that's the whole idea is that this is a cancer that we can prevent and basically that prevention is lifesaving. That's absolutely right. Well, let's understand the polyps. So, let's say, a woman developed breast cancer, she had no warning probably. There were the cancer cells shown on mammography or a lump confirmed by biopsy. But in colon cancer we have this very typically slow-growing cancer, right, and we have the warning sign, if you will, of the polyps that are not yet cancerous and we have time, if you will, to intervene. Is that correct? That's right. So really what we've learned over the last I'd say about 30 years is that almost all colon cancers come from these colon polyps. And the polyps probably take maybe five to 15 years to form, and then once they form it probably takes them another 10 to 15 years to go on to change from a polyp into a cancer. So it is a slow-moving process. So you could say, well, if that's the case why isn't it that we're able to detect it at a time when it's early on in the cancer formation process and where it's more easily treatable. And the problem is during that whole polyp phase of cancer formation, doesn't cause any symptoms so people don't know that they have colon polyps. But really the time to find the polyps is the time when they're not having symptoms or to find, to basically find the polyps before they have a chance to turn into cancer. 2

So the whole goal behind screening for colon cancer really is, in my mind, more screening for colon polyps and removing the polyps, not even letting them get a chance to where they can turn into a colon cancer. All right. So let's talk about the way screening goes on now. So people get a physical, and sometimes the doctor will give them that little card for the occult blood test, and my understanding is if there's a sign of blood even if you can't see it in your stool then there needs to be further investigation. Now, it can be hemorrhoids or other things that are going on, some kind of fissure, if we can talk about that, but also it could be an indication of colon cancer. Is that still at the point where there are polyps, or is that where the blood may really be a sign that cancer has developed? It could be a sign of either one, and we know that the stool cards can detect the colon polyps though they tend to bleed less often than the colon cancer. So if we look at technically how the test performs it's probably a more accurate test for colon cancer than it is for colon polyps, but it will detect both. One of the big issues I think we need to keep in mind is who the right people are who should be having those stool card tests done. Right. Who Has Increased Risks for Colon Cancer? And this gets back to what do we know about what people are at risk for developing colon cancer. And what we recommend currently is that people over the age of 50 who have a colon have colon cancer screening done. And you could make the argument of well, why 50? Why aren't we starting at age 40 or 30 or even 20? And what we know is that colon cancer is relatively infrequent under the age of 50, so the equation then starts factoring in to that fact and also the fact that when we go looking for colon polyps the looking has a cost that goes along with it. And the cost is inconvenience. The cost is dollars. The cost is potential risk from some of the types of screening tests that we do. So what we want to do is make sure that we have the right risk/benefit balance so we know that if someone decides to have colon cancer screening done that they're likely to get a benefit from it and not have something adverse happen. So as a consequence of that we usually don't recommend doing screening tests because the likelihood of a false positive exam is so high for people under the age of 50 except, in a few situations. And one of those situations that is true of about one in three or one in four people in the United States is whether they have a 3

hereditary increased risk for developing colon cancer. We know that about a third to a half of colon cancers have a significant genetic risk that puts people at a higher risk of forming colon cancer than other people in the United States. And the way we know that is that colon cancer will be occurring in that person's family. So if that's the situation we usually recommend looking for the colon cancer with screening tests starting about five to ten years younger than what we call the general population, so that would mean starting around age 40. Or if there's someone in your family who has had colon cancer at a young age, let's say 35 or 30 years old, we recommend looking ten years younger than the youngest person who has had colon cancer in the family. Wow. Well, you described my situation along the way. So the fact that my mother died of colon cancer in her late 70s, but it was developing now I know for years, and my dad would be found routinely to have these precancerous polyps, that meant for Andrew starting in my 40s. And I did, right? That's right. Okay. Now, how far does that carry forward? So, first of all, for my siblings it would be the same. What about if there's no colon cancer in my case, what about in my children? What Role Do Genetics Play? Right. So the further you get away from people who had colon cancer in the family, and when we talk about that from a genetic standpoint what we talk about are first-degree and second-degree relatives. So first-degree relatives are all the people that you're kind of immediately connected to, so your brothers, sisters, parents and children. And second-degree relatives are one generation away from that, so in this case we'd be talking about grandchildren. We know that that basically halves the risk of developing colon cancer. And those people unless there are a lot of people in the family who are second-degree relatives who have had colon cancer, we usually don't recommend any specific change in the screening recommendations. So we'd recommend again starting at age 50 if you've got a colon. What we know when we look in families who are at risk for colon cancer is the younger the age of people in the family who have had colon cancer and the more of them, the higher any other family member's risk is for developing the cancers. 4

There's a story I like to tell. So years ago for the American Cancer Society I did an interview about colon cancer, and there was a fellow who had been treated for it who told this story. He was one of six kids, and the oldest brother died of colon cancer. And so the other five are standing around the gravesite, saying their final good-bye, and he turned to his siblings and said, Well, have you been screened, Have you been screened. They all say no. They were all I think in their 40s and 50s. And they made a pact at their brother's grave side that they would. And, sure enough, two of them were discovered to have early signs of colon cancer. So I said to him, are you saying that your brother's death may have saved your life, and he said, Absolutely, because, he said, I don't think we would have been screened. So let's move on then and talk about screening. It sounds like we can't put a lot of faith in the little card you might get at the doctor's, the little occult blood test. Many of us at the appropriate time should move on to colonoscopy. And we've heard more about that in recent years. And if you talk to a friend or a family member who has had it, they said, well, you know the preparation wasn't the greatest, although certainly you kind of knock people out in sort of a twilight condition and you don't remember what happened afterwards. Where are we now in the safety of that and in the effectiveness of it and also maybe making the preparation a little easier? Colonoscopy Preparation Those are all really good questions, and we as gastroenterologists recognize that the getting ready part of the colonoscopy is really the toughest part. And we will agree with you in terms of out of all the screening tests that are currently available for doing colonoscopy, which one is the most accurate. The most accurate one we do think is colonoscopy, so that's what we are currently recommending in the United States. Although, just as an aside, one thing that is it interesting is if you look at other countries around the world who have a high risk for colon cancer many of them do not recommend colonoscopy and that's a reflection of how much it costs to do colon cancer screening by colonoscopy compared to doing the stool cards. So there are places in mostly European countries are just starting to get going with doing colon cancer screening in using the stool cards because they can't afford colonoscopy. So I think that's one of the wonderful things about being in the United States is that we've got the resources to be able to offer this. Obviously the downside, though, is that getting ready for colonoscopy means that you have to go on that diet and you have to drink all that fluid that makes you have cramps and diarrhea, and so we'd really like to figure out some way where we don't have to do that. There are a variety of different ways that you can get ready for the colonoscopy. I don't know if they really vary that much materially in terms of how you feel when you're getting ready. There are little pills that you can take and 5

you can drink water along with that, or there's a big gallon jug of fluid that you can drink that cleans your colon out, or you can drink two little basically soda can-size fluid drinks called Fleet's Phospho-soda. Unfortunately, they all need to do the same thing which is basically get your colon cleaned out well enough so that someone like me can get a good look at it using a tube that has a camera and a light on the end of it, which is essentially the colonoscopy. And getting the colon cleaned out really is important because if the colon is not cleaned out well it's really hard to see what's going on in the colon. So that is something that we would emphasize a lot with people who are going do get colon cancer screening done in that even though it's tough and uncomfortable to go through the preparation process, it's really important that it be done well. Right. Let's talk about that for a minute. Now, if you see something like a little, precancerous polyp you can then snip it out right then, and the person has not been diagnosed with cancer, and they will need to be followed but that was the purpose of the exam, both screening and then intervening in a preventive way, right? Right. So let's start with if you find something, let's say just one little thing, and I've had that too, how often would somebody have to come back? When would they have to have a colonoscopy again? Currently, what we recommend is that someone has a colonoscopy and they have one large polyp found or two or more smaller polyps that they have a repeat exam done in three years. If only one small polyp is found then we recommend a follow-up exam in five years. And if no polyps are found we recommend a follow-up exam in ten years. So it's a little bit on the sophisticated side, but basically if you've got polyps what we know is that that means there's a high chance that you're form more polyps in the future, so what we recommend then is looking, basically shortening the interval by half, so about three to five years rather than ten years. Dr. Grady, there's been publicity lately about something called virtual colonoscopy. Help us understand that or maybe different experimental variations of that and whether any of this is ready for prime time where somebody would not have to have a tube put inside them, and this could be done another way, and would it make a difference as far as the preparation goes. 6

So that's an area that's been ongoing, really exciting development. And it comes back to what we're trying to do to figure out ways to do colon cancer screening where people don't have to have a preparation and then, for a colonoscopy. So one of the ways at that is using this technique called virtual colonoscopy or the technical term for it is called CT colonography. And basically that's using a CT scanner to look at the colon and it basically can recreate what we can see with the colonoscopy but using X-rays. Currently the way we do that still requires the same preparation as is needed for a standard or what we call an optical colonoscopy. And what we're finding now is using, with a lot of revisions that have gone on it's looking like virtual colonoscopy is probably getting pretty close to being as accurate as optical colonoscopy. Now, one of the big issues that comes up that you alluded to is if on virtual colonoscopy a polyp is found it can't be removed, and so what that means is that a standard colonoscopy has to be done as well as the virtual colonoscopy so that not only can we find that polyp but we can also remove it. So a lot of places, including the University of Washington and Seattle Cancer Care Alliance, are developing protocols now where if someone has a virtual colonoscopy they can then go on to have a standard colonoscopy done on the same day so. That way a person doesn't have to do two preparations for colon cancer screening. So where people want to go next with this, people meaning gastroenterologists and researchers in this area, is using ways to do virtual colonoscopy where you don't have to do the getting ready, the preparation part. And there's been some work done where basically a dye can be mixed in with some food that's eaten before the exam, and then the stool can be subtracted by the computer that does the x-ray study. That's coming along as well, although it's not accurate enough to replace colonoscopy or the standard way of doing virtual colonoscopy. So I'd say probably in a few years it might have that potential. One of the things I really want to emphasize though is that there are a lot of exciting technologies that are coming along that all look like they may be able to replace colonoscopy in the next five to 20 years. We just don't know when they're going to be ready, and I would really discourage people who are over the age of 50 and who are eligible for colon cancer screening to wait for something new to come along. Because I think that's essentially like putting a bomb in your pocket and deciding that you're just going to wait and hope that the bomb doesn't explode while you're waiting for something to come along that might be able to defuse it. Right. 7

I think we have very accurate tests that have some inconvenience to go along with them. And the thing that's so amazing to me about colonoscopy is that this is really a cancer preventing method. And the reason why I find that so amazing is that if we look at other screening tests that we do for other types of cancer, such as mammograms for breast cancer or the blood test for prostate cancer, the PSA level, those can detect early cancers but they can't detect the cancer at a stage before it's a cancer. And we can do that for colonoscopy. We can detect a colon polyp, and we can remove it before it even has a chance to become a colon cancer. So for me that's really profound. So not only are we screening for early cancers but we're actually preventing colon cancer from occurring. Right. That's a good point. I wanted to raise one about earlier intervention in colon cancer. I remember vividly walking with my mother as we were headed to the car to go to the oncologist for her to receive treatment for advanced colon cancer. She was really angry, as many people diagnosed with cancer are, you know, why me. But she also recognized that she had hesitated for a long time to go to the doctor, and she confided in me that she'd actually had rectal bleeding for a while and just didn't tell anybody. And the reason she didn't was because my mother was somewhat overweight and didn't want to go to the doctor and have him tell her that she needed to lose weight. And of course she had kind of her priorities wrong of course, and she then recognized it. So I certainly would agree with you the importance of people just getting it done. If there were signs, either some abdominal pain or some rectal bleeding, is it possible that she could have been colon cancer intervention where again it would have been earlier and the outcome would have been much better. That's absolutely right. And you bring up a really good point. And that is that cancer of any type is scary, and a lot of times I think what happens is that people are so scared by the fact that they might have cancer that they choose not to do anything. And that's really not the way you want to be thinking about cancer. You really want to be thinking, well, sometimes it happens, the sooner you know about it the better it can be treated, the easier to go through the treatments and the more effective treatments are. And that's particularly true for colon cancer. So for someone like in your mother's situation if colon cancer is caught at an early stage, a lot of times it requires an operation but it's a fairly straightforward operation. It very rarely results in people needing to have one of those bags, the colostomy bags. With modern surgical techniques almost always we can reconnect the colon so that it functions normally. And if we catch it early we're successful over nine out of ten times in completely curing someone of the cancer. If we wait and the cancer has had a chance to spread into the surrounding area, we're about maybe successful six to seven out of ten times. So still not bad. But if we wait 8

even a little bit longer and the cancer has had the chance to spread to places like the liver or the lungs where it can go, then we're only successful maybe one in 20 times in curing someone. So that gives you a spectrum where if we catch it early we're successful 19 out of 20 times, where if we catch it late we're successful only about one out of 20 times. The story I'm always reminded of is that President Ronald Reagan, who died of complications of Alzheimer's had been diagnosed with earlier stage colon cancer, had the surgery that you mentioned and the, you know, colon reconnected, and that is not what led to his demise. He led a pretty long life. Certainly there are many stories like that. We have a couple of questions we've received. One is from Meredith from Mount Pleasant, Utah, and she says, "What warning signs can patients be alert to when it comes to colon cancer?" So obviously they should be screened. They may not have felt anything at all with precancerous polyps, but what are signs they should be on the lookout for? I'd like to start by saying the most common sign of colon cancer is no symptom at all, and that's why screening is so important. But if symptoms do develop it's usually a sign that a cancer is there, and it may be slightly more advanced but still doing something about it sooner rather than later is the right strategy because that gives the best chance to cure it. The things that people may notice is blood in the stool, a change in bowel habits, so maybe there's a change in the size of bowel movements. Sometimes they can become very thin as a result of the cancer. Sometimes there can be a feeling of being bloated or being constipated. Sometimes there can be pain in the belly. The problem is that most of the symptoms are what we call nonspecific symptoms, so there's lots of things that can do that. All those things I just mentioned, my guess would be over the last week that you probably had those symptoms. I know I have. And so it's hard to know how much faith to put in those symptoms as a consequence to that. Is there a diet people can follow that will lower their risk of colon cancer? Because you mention the rates vary by country. What could we do as individual Americans to lower our risk? There are things that you can do in terms of diet. We're still trying to figure out which things in the US diet are the ones that seem to increase the chance of getting 9

colon cancers and which ones seem to decrease the chance. We think about half of the risk for colon cancer does come from diet. What we do know is that there is a strong association with red meat. So we typically recommend that people limit the amount of red meat that they eat as a way to help prevent getting colon cancer. And it's also important to know how the meat is prepared seems to make a difference. So if the meat a grilled, that seems to have the highest chance of increasing the risk for colon cancer as well as for other cancers including prostate cancer and breast cancer. We think what happens is that when the meat a grilled, when it gets that really nice color on it where the gets burnt a little bit, that burnt meat actually has cancer-forming chemicals in it. So we recommend people limit the amount of meat that they eat. And also increase the amounts of fruits and vegetables. And my recommendation is always things in moderation. Whole foods are better than processed foods, and limiting the amount of red meat consumption in particular seems to be beneficial. That's all good information. Now, I know at the Seattle Cancer Care Alliance and the University of Washington it's a big research institution as well. Where are you with your work in I think what you call biomarkers? So that's for a blood test where you may be looking at a more sophisticated way at people's stool, there can be indications of whether colon cancer is at work? Biomarkers as an Early Detection Tool That's right, and there's been a lot of interest in biomarkers. Again getting back to this idea if we had a biomarker it would be a way to get screened for colon cancer where you wouldn't have to do the preparation part for colonoscopy unless you knew that you had a polyp. Then, in my mind, it would be a lot easier to go through the whole process because you'd thinking, Oh, now I'm going to have a colonoscopy done but I know I'm not doing it just to look for polyps, I'm actually having it done so that those polyps can be removed. So when we talk about biomarkers really what we are talking about are chemicals or substances that can be in blood or in urine or in stool that can indicate whether someone has a colon polyp or a colon cancer. We've been very interested in a chemical that's called methylated DNA. And methylated DNA is something we find in normal tissue, but we can also see it in cancer tissue. And what we look for are specific parts of the DNA that are methylated. And what happens is that the cancer cells have figured out that if they can methylate regions of DNA that have genes in them that are genes that are called tumor suppresser genes that that can help the cancers form. So what we've been doing at the Fred Hutch Cancer Research Center is looking to see whether there are specific methylated genes that can be used as colon cancer 10

specific biomarkers. And we've been looking in blood samples, and we've found that blood tests can detect about a third of people who have colon cancer. We've also been looking in stool samples from people who have colon cancer as well in urine samples to see whether we can detect these methylated genes in those, in urine or in stool samples. And what we find is that we can. We can detect it in about half of people who have colon cancers and slightly less than that in people who have colon polyps. So we're excited about the fact that these tests are working. And in fact there's even a test that if you wanted you can have your doctor order for you right now that looks for tumor DNA in stool samples that's more accurate than the stool card tests, but it's still not nearly as accurate as colonoscopy. So I think where all these biomarkers, including the ones that we're working on as well as the one that you can order from your doctor's office, is that they're not as good as colonoscopy. And the challenge for us working on biomarkers is that we need to make a test that's going to be very close to the performance of colonoscopy. And colonoscopy can detect for large polyps, almost all of them. It's about 95 percent accurate for detecting large polyps and for detecting colon cancers. So that's a very high benchmark for these biomarkers to be able to get to, but it's certainly something we're striving for. These tests are showing promise, but they're not quite ready yet to replace colonoscopy. Well, anybody who has had a colonoscopy wishes you well with that. But I would say that having had a parent who died from the complications of colon cancer I understand how important it is for me to be checked from time to time. And I would urge anybody listening, please, following those guidelines that Dr. Grady set out, and they're well known from the American Cancer Society and I'm sure you can talk to your primary care doctor, they'll reinforce it too, it really is something that should be part of your life as you get older, and if it's in your family, then starting sooner. Dr. Bill Grady, thank you so much. I think we've covered it pretty well, don't you, and hopefully saved some lives and had earlier intervention for people in the process. That's right. It's been a real privilege for me to have a chance to talk to you today, and I really appreciate the opportunity. Thank you. We've been visiting with Dr. Bill Grady, who is a gastroenterologist. He's not just that, he's chief of the division of gastroenterology at the University of Washington. He's also medical director of the Gastroenterology Cancer Prevention Program at the Seattle Cancer Care Alliance, and he's an associate member of the 11

Fred Hutchinson Cancer Research Center. I want to mention that on Saturday June 14th at the Fred Hutchinson Cancer Research Center there will be a big survivorship program. It will be the second annual meeting, Moving Beyond Cancer, and it's moving beyond cancer to wellness and it's an educational event. And the key speaker will be Lance Armstrong, the famous cancer survivor and of course Tour de France winner, it will be his mom, Linda Armstrong Kelly. And the event will also have breakout sessions and all sorts of experts on nutrition, complementary and alternative medicine, physical therapy, dealing with fatigue, pain, relationships and sexuality if you're dealing with cancer, insurance rights for sure, all sorts of research information about survivorship, cancer genetics. We were talking about if colon cancer is in your family. And even things about helping with your cognitive function. Some people who have done through cancer treatment say, well, is there a chemo brain. And that will be at the Fred Hutchinson Center campus in the Thomas Building. There's more information on the following website: survivor@fhcrc.org, survivor@fhcrc.org. Here's a phone number: 206-667-1960. I hope you can join us. On our next program sponsored by the Seattle Cancer Care Alliance we'll visit with Dr. Evan Yu, and we will actually talk more about cancer biomarkers, what we started to talk about with Dr. Grady, and so we'll be looking at how cancer biomarkers can help personalize or individualize cancer care for you. As always, I learned so much. Knowledge can be the best medicine of all. I'm Andrew Schorr. Thanks for joining us for this Patient Power webcast sponsored by the Seattle Cancer Care Alliance. See you next time. Please remember the opinions expressed on Patient Power are not necessarily the views of Seattle Cancer Care Alliance, 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. 12