Colorectal Cancer Screening

Today we are discussing colorectal cancer screening, including the results of two recently published studies in the New England Journal of Medicine that show the long-term effects of colorectal cancer screening, using two different approaches. We are joined by two gastroenterologists, Dr. Douglas Corley and Dr. Theodore Levin, who are also cancer researchers at Kaiser Permanente Northern California Division of Research, where Dr. Levin directs the colon cancer screening program. Both Dr. Corley and Dr. Levin wrote an editorial in the New England Journal of Medicine about the new long-term screening trial results.

-Interviewed by Anna Azvolinsky, PhD

Cancer Network: Dr. Corley, let’s start with you. Could you tell us what the current screening guidelines are in the United States? What methods are recommended, for whom, and how often?

[[{"type":"media","view_mode":"media_crop","fid":"18011","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3356453390920","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"1192","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Douglas Corley, MD, MPH, PhD","typeof":"foaf:Image"}}]]Dr. Corley: The current guidelines really work to put people into two groups. Are patients at average risk or are they at increased risk? For those who are at increased risk, that is mainly related to having family members who have had a history of colon cancer, close family members such as parents or siblings. For those patients, it is recommended that they have colonoscopies. The time to start depends on when their family member was diagnosed. If it was at a young age, then it is recommended that the patient also starts screening at a younger age. For the average-risk person, which is most of the people in the United States, colon cancer screening is recommended to start at age 50, and the guidelines include several different types of colon cancer screening, including colonoscopy; the stool-based tests, which look for small amounts of blood in the stool; as well as sigmoidoscopy. One of these methods is recommended starting at age 50. In terms of how often, this varies depending on the method. Colonoscopy is thought to be more sensitive, but it is also higher risk and more intrusive, so this is recommended for someone every 10 years if the initial exam is negative. The stool-based tests, which are much less invasive and easier to do in general, but are less sensitive, are recommended approximately once a year. The sigmoidoscopy is an endoscopy exam that looks into the colon but does not require sedation, and is less invasive and onerous. This is recommended every 5 years per the guidelines.

Cancer Network: One of the New England Journal of Medicine publications was the 30-year follow-up of the Minnesota Colon Cancer Control Study with fecal occult blood testing, which you just described, Dr. Corley. Dr. Levin, could you describe this trial and these new results?

[[{"type":"media","view_mode":"media_crop","fid":"18012","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_6155167186676","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"1193","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Theodore Levin, MD","typeof":"foaf:Image"}}]]Dr. Levin: Of course. The Minnesota Colon Cancer Control Study trial, which was the first randomized trial in colon cancer screening, was originally published in 1993 and looked at a population of patients who were randomized to receive either a fecal occult blood test annually or biannually compared to no screening. This was the first study to show a benefit for any screening test on colorectal-specific mortality. For this paper, this was a long-term follow-up through 30 years of over 33,000 participants, and demonstrated that the mortality benefit, even after the trial had stopped running, persisted. People who were in the annually screened group were at 32% lower risk of colorectal cancer–related mortality, and in the biannual screening group, 23% lower risk of mortality from colorectal cancer. There was no observed reduction in all-cause mortality, so people didn’t actually live longer because they were screened, but they were less likely to die from colon cancer. Men seemed to benefit from the screening more than women, and there were subgroups of patients who benefited a little bit more. Particularly, among the men who were between 60 and 69 years of age who went through the screening, they seemed to benefit the most. For younger women, there was no discernible benefit, for those under the age of 60. The importance of this study is that the long-term effects of screening do seem to continue and pay off even after the screening has completed.

Cancer Network: The second publication assessed a 22-year follow-up of colorectal cancer incidence after lower endoscopy screening. Dr. Corley, could you talk about these results?

Dr. Corley: This is a different type of study; this is an observational study, not a randomized trial. People were not assigned to one group vs another. But this was a very large study; they evaluated about 88,000 people from two different groups. One was a Nurses’ Health Study and the other is what is called the Health Professionals Follow-Up Study, which included other health professionals, such as physicians. These studies are extremely large, powerful, and carefully done. What they do is they ask people to record what is happening with them, such as their diet, their medical conditions, their medications, every 2 years. What they also ask is whether someone has had a colonoscopy or a sigmoidoscopy, and they followed them over time. For this study, it was for 22 years, as you noted. They looked to see among the people who had a colonoscopy or a sigmoidoscopy, were these people at a lower risk for colon cancer compared with those who did not have these procedures.

What they found is that after a colonoscopy, there was a little greater than a 50% reduction, so people were about half as likely to develop colon cancer after having a negative colonoscopy. They also found that there is about a 40% reduction in cancer risk after a colonoscopy that found a polyp, a type of precancerous lesion. The thought there is that having the exam done either identifies you as being in a lower-risk group, someone who is unlikely to develop cancer, or it may find something such as a precancerous polyp that can be taken out and then that would reduce your risk in the future. They also found that sigmoidoscopy had a reduction of about 40% or so in terms of the risk of colon cancer. Again, a sigmoidoscopy is a more limited exam looking at the left side of the colon, and they found that the reduction of colon cancer risk for that test was mainly related to the area that was evaluated, the left side of the colon.

So, a few things with this that were interesting-one is that the risk of colon cancer stayed down for a long time, so if you had had a normal exam, your reduced risk for having colon cancer was up to 15 years. And if you had more than one colonoscopy that was negative, your risk was quite low. The other thing that the authors found that was consistent with the current guidelines is that the risk is higher among those who have a family history and also among those who have what are called high-risk polyps. These are polyps that are large or have more concerning precancerous changes in them. For those patients, the risk did not stay down as long, the risk rose again after 3 to 5 years. Again, that is consistent with current guidelines of how we use current colon cancer screenings for those patients. They are not recommended to wait for 10 years, they are recommended to wait a shorter amount of time before their next colonoscopy.

Cancer Network: How will these results affect recommendations for screening going forward? Dr. Levin, let’s start with you.

Dr. Levin: I think that these results confirm the guidelines. As Dr. Corley was mentioning, there are some recommendations we have for follow-up and intervals for colonoscopy that were based on expert opinion, that perceived increased risk but did not have firm grounding in any clinical evidence, particularly the frequency of colonoscopies for those with a family history of colon cancer and the follow-ups of some of the more worrisome polyps that he mentioned. This was really good data for those two things. Also, the fecal blood test still appears to be effective and to have value even after the screening is completed. The interesting thing about this field, if I can branch forward a little bit, is that both of these tests have really improved compared to the time when they were used in these studies. The colonoscopists today are much better at finding flatter polyps. We still have much more work to do on those improvements, but we are much more attuned to looking for those in colonoscopy practice. And the fecal blood tests are dramatically different tests now than they were during the time of the Minnesota study. We are using a chemical test specifically for human hemoglobin, which is more sensitive than the test used in the Minnesota study. It detects more cancers and precancerous polyps, and it is also more specific; there are fewer false positives. But both of these studies serve to reassure us that we are on the right track with our current screening guidelines.

Cancer Network: Dr. Corley, do you have anything to add?

Dr. Corley: Just to reinforce, these results are reassuring, particularly for the long-term follow-up. I think one of the questions was how long should you wait to have another screening exam, as far as the endoscopy exam. There are a lot of questions on the 5- to 10-year window, whether that is okay. This suggests that it is, that the risk may even be reduced much longer than that. If we compare this with some other types of cancer screening, we are talking about huge reductions in risk, reductions in risk that are 40% to 60%, compared with something like mammography for breast cancer screening, where the risk reduction is only 25% to 30%, so these are much bigger reductions. Again, I think this is reassuring that the current guidelines are on track.

Cancer Network: Are there ongoing, either observational or randomized, studies that are comparing the effectiveness of different screening methods that you could highlight?

Dr. Levin: There are two that I can think of. One is in the VA (Department of Veterans Affairs) system in the United States. The study is called CONFIRM, which is a randomized trial of immunochemical fecal blood test vs colonoscopy for screening. In that study, patients are being referred to the study for screening, and then randomized to get one or the other strategy and being followed up for 15 years. This study is just getting started, so we won’t have an answer for a while, but it is the first American study, a large American study. The goal is to enroll 50,000 people to give us an answer of which test is better. Of course with the immunochemical test, people have to do it every year, and with a colonoscopy, you do it once and then wait for 10 years if it is negative. There are different issues with adherence, and whether patients can consistently adhere to the fecal test annually is a question.

The other study is one in Barcelona, which is of a similar design. People are being randomized to either immunochemical testing or colonoscopy. In that study, they published the initial results after the first round of screening. There was a higher adherence rate or completion of screening for those people randomized to the fecal test compared with the colonoscopy, and that translated to similar detection of cancer between the two groups. Although the colonoscopy side did pick up a few more of the precancerous polyps, the fecal test will have more chances to detect those polyps in subsequent rounds of screening. In that study, the fecal test is being done every other year rather than every year.

Cancer Network: Thank you so much to both of you for joining us today.

Dr. Levin: Sure!

Dr. Corley: Thank you very much for having us!