Greetings, and thank you to the course organizers for inviting me to be part of this important course. My name is Charles Kahi from Indiana University, and my task is to provide an update on colonoscopy screening and surveillance guidelines. As everyone in the audience is aware, colorectal cancer screening has been an unequivocal success story in the United States, and we have observed consistently decreasing trends in colorectal cancer incidence since the mid-1980s in individuals aged 50 to 65. And this applies to all colorectal cancer, colon-only cancer, and rectal cancer. However, and unfortunately, we have been observing a reverse trend in individuals younger than 50, with gradually increasing incidence rates since the mid-1990s, particularly for rectal cancer. And it is not just a matter of increased incidence rates. We are actually seeing what is referred to as a birth cohort effect, where individuals born in successive generations actually are carrying forward an increased risk of developing colorectal cancer. So that currently, it's estimated that for adults born around 1990, these individuals have twice the risk of colon cancer and about four times the risk of rectal cancer compared to those born around 1950. And this is important to understand, because these birth cohort effects actually suggest early life exposure and or repeated exposures in younger individuals that are driving this increased colorectal cancer incidence. And it does seem that this early adult-onset colorectal cancer may be a disease of affluence because other developed countries are actually reporting similar trends as the United States. So currently, early adult-onset, or EAO-CRC, constitutes about 11% of all colorectal cancers and 15% of all rectal cancers. And in reviewing SIR-18 data from 2000 to 2016, alarming trends are seen in successively younger age groups. For example, in those who are 20 to 29 years old, there was an annual percent increase of about 5.6 for all colorectal cancer and 1.6% for rectal cancer. Now it's important to qualify some of these numbers. Most of these increases are referred to in relative rates. The absolute early adult-onset colorectal cancer rates actually remain somewhat low. And between 2013 and 2017, these increased from 7.29 to 8.36 per 100,000 compared to declines from 123 to about 111 per 100,000 in those who are 50 and older. However, the trends are consistent and alarming. And currently, the incidence rates in 45 to 49-year-olds are similar to those who are 50-year-olds back in 1992, prior to the initiation of mass colorectal cancer screening in the United States. Colorectal cancer mortality rates are on the rise in the 40 to 49, and also alarmingly in the 50 to 59-year-old age groups. These alarming epidemiological trends, together with modeling analysis, have informed a new set of guidelines, which basically recommend starting screening at the age of 45. The first such guideline was set by the American Cancer Society in 2018, and it was followed in quick succession by most professional organizations, including the U.S. Preventive Services Task Force, the American College of Gastroenterology, the National Comprehensive Cancer Network, and the U.S. Multi-Society Task Force, which includes the AGA, the SGE, and the ACG. Essentially, all guidelines recommend or suggest starting screening at the age of 45, with the caveat that all of these recommendations are qualified recommendations, owing to the paucity of empirical data showing that screening in this age group is effective. Let's review some of the clinical features of early adult-onset colorectal cancer. Most of these are average risk. There is no family history of colorectal cancer, no inflammatory bowel disease, and about 80% have no identifiable genetic cause, with Lynch syndrome accounting for about 10% of all colorectal cancer cases in those who are younger than 50. As mentioned before, many of these cases tend to be in the rectum and left colon, as opposed to the proximal shift that's normally observed in older individuals. And nearly 90% of early adult-onset colorectal cancer cases are detected because of symptoms, which is rectal bleeding in most situations. Other symptoms can also be present, such as abdominal pain and change in bowel habits, but rectal bleeding is the most alarming presenting symptom. Most early-onset colorectal cancer cases are advanced at presentation, 70 to 80%, and they are not necessarily explained by a delay of diagnosis. I mentioned earlier that guidelines were limited by the relative paucity of empirical data supporting screening in individuals 45 to 49 years old. However, we do have retrospective data suggesting that this practice is likely to be effective and as impactful as screening in older individuals. For example, the systematic review and meta-analysis of 17 studies, including about 52,000 individuals younger than 50 years who underwent screening colonoscopy, showed a very comparable advanced neoplasia prevalence in individuals 45 to 49 years old compared to those who are 50 to 59 years old, 3.6% versus 4.2% in the study, suggesting, again, albeit indirectly, that the impact of screening in the 45 to 49-year-old group is likely to be similar to that in older groups. We have covered the major update to guidelines, which is when to initiate screening. We will turn our attention briefly to an equally important topic, which is when to stop screening and surveillance. This is very important because the elderly represent a growing segment of our population and also because in the elderly, the benefits of colorectal cancer screening may be offset by worsening health and decreasing life expectancy. Most major professional societies make qualified recommendations regarding when and how to stop screening and surveillance. The American Cancer Society, for example, recommends screening until the age of 75, provided the individual is in good health with life expectancy greater than 10 years, and then to individualize colorectal cancer screening decisions for ages 76 to 85 based on a variety of factors, including patient preferences, life expectancy, health status, and prior screening history. Most major organizations make qualified recommendations regarding this issue, again, due to the paucity of high-quality evidence. The U.S. Multisociety Task Force goes a step further with more specific recommendations regarding taking into account prior screening history. Namely, if an individual is up-to-date with screening and with negative prior screening tests, then it is okay to consider stopping screening at the age of 75 or if life expectancy is less than 10 years. Conversely, if there is no prior screening or no high-quality prior screening, then consider screening up to age 85, taking into account the age of the patient and associated comorbidities. The major portion of this presentation will now be devoted to surveillance colonoscopy. It is very important to get surveillance right for a variety of reasons. An estimated 25 to 30% of all colonoscopies are done for surveillance indications, and unfortunately, this is significantly misused with both over- and under-utilization of surveillance colonoscopy. Different studies have put this at ranging from 25% to 50%. And it's important to get surveillance colonoscopy right because it contributes significantly to decreasing the burden of colorectal cancer. In fact, in one study, it was estimated that surveillance colonoscopy during 10 years of follow-up prevented about 30% of colorectal cancer cases. So while most of the benefit is derived from the baseline screening, about one-third is to the credit of subsequent surveillance. We will cover now the U.S. Multisociety Task Force update to post-polypectomy surveillance, which was published in 2020. The new guidelines provide significantly more granularity than the previous iteration in 2012. For high-risk adenomas or advanced adenomas, the recommendations are unchanged. So adenomas larger than a centimeter with villus histology or high-grade dysplasia, the guidelines still recommend a three-year surveillance interval. The major updates concern smaller adenomas, what was referred to as low-risk adenomas previously, one to two adenomas smaller than 10 millimeters, where the previous guidelines recommended five to 10 years, this has become seven to 10 years. And for patients who have three to 10 adenomas, this group has been broken into two major categories, three to four adenomas less than 10 millimeters. And for these patients, a three to five-year interval is recommended. And for individuals with five to 10 adenomas, a three-year interval is recommended. These recommendations are supported by multiple studies. The following two were published actually after the guidelines. However, in hindsight, they largely support what the Multisociety Task Force guidelines Multisociety Task Force guidelines had recommended with regarding to risk stratification and surveillance recommendations after polypectomy. In this meta-analysis, for instance, grouping 12 studies with half a million patients with mean age 59 years and mean follow-up of 8.5 years, colorectal cancer incidence in patients who had a low-risk adenoma at baseline was slightly higher, but roughly comparable to those who had no adenomas at baseline with an odds ratio of 1.26. Mortality was no different. Colorectal cancer-specific mortality was no different between those two groups. Contrast these rates to those seen in patients with high-risk adenomas, where both colorectal cancer incidence and mortality were significantly higher than the other two groups. Broadly, this supports the recommendation of extending the surveillance interval in patients who have one to two small adenomas at baseline. Similar evidence supports the recommendations in the case of serrated polyps. For example, in this study, grouping 123,000 participants in the Nurses Health Study and Health Professional Follow-Up Study with participants followed for a median of 10 years, the hazard ratio for baseline small serrated polyps or non-advanced adenomas was not increased and was about 1.2. Conversely, the hazard ratio for incident colorectal cancer was similar for baseline advanced adenomas and large serrated polyps. We have mentioned that one of the most important updates to the surveillance guidelines is that individuals with one to two adenomas less than 10 millimeters should undergo surveillance in 7 to 10 years. However, we also showed that the risk associated with low-risk adenomas at baseline does not seem to be significantly different than that with patients with no adenomas. Now, what is the reason that the Multi-Society Task Force recommends a 7 to 10-year interval instead of just 10 years for these individuals? And the reason is, in those who have low-risk adenomas, it is conceivable that many have undergone subsequent surveillance colonoscopy, and hence some of the protection is derived from those surveillance examinations as opposed to solely the baseline screening colonoscopy. So how does one make decisions between 7 or 10 or an interval intermediate to these two for patients with low-risk adenomas? And these are some rules of thumb to follow in making such decisions. In patients who are older, male, possibly with metabolic lifestyle factors, proximal location, high cumulative adenoma burden based on prior examination, and notably, if at least one of the adenomas is 6 to 9 millimeters within this less than 10 millimeter broader category, then it's probably safer to err on the 7-year side of surveillance. If these factors are not present, the patient is younger, female, with a healthy lifestyle, no prior adenomas, and the adenomas are less than 5 millimeters or less, then a 10-year interval is appropriate. The Multi-Society Task Force recommends the following intervals for surveillance based on baseline adenoma findings. As we mentioned, 7 to 10 years for patients with 1 to 2 adenomas less than 10 millimeters, 3 to 5 if there are 3 to 4 adenomas less than 10 millimeters, 3 years for most other situations, including advanced adenomas and in the situation of having 5 to 10 adenomas less than 10 millimeters. Serrated polyp surveillance guidelines follow broadly a similar approach, with the important caveat that the strength of the recommendations are all weak because they are based on very low quality of evidence. Contrast that with the quality of the evidence supporting adenoma surveillance. In patients who have 1 to 2 cesareated polyps less than 10 millimeters, the guideline recommends 5 to 10-year surveillance, and 3 to 5 years in the case of 3 to 4 serrated polyps less than 10 millimeters. And then similar to the adenoma counterparts, in case of multiplicity or large serrated polyps or polyps with dysplasia, the guidelines recommend 3 years. The guidelines also make recommendations for second surveillance based on the results of baseline and first surveillance findings, and these are broadly similar to surveillance guidelines for first surveillance. With the exception of if the patient has an advanced adenoma at the baseline procedure. And in that case, if there is a normal, if the first surveillance colonoscopy is normal or reveals 1 to 2 tubular adenomas less than 10 millimeters, the guidelines recommend a 5-year follow-up as opposed to 10 and 7 to 10 in the other situations. This slide basically summarizes the entire guideline, but presents the surveillance recommendations based on intervals, and then shows the findings at colonoscopy that would qualify for such a surveillance interval. Take home points. As we saw before, 45 is the new 50. 45 is the new 50. Pay attention to younger patients with symptoms, particularly rectal bleeding, which seems to be closely associated with increased risk of early adult-onset colorectal cancer. Screening and surveillance after the age of 75 should be guided by health-adjusted life expectancy, but also take screening history into account when making these decisions. And finally, de-intensify surveillance in individuals with low-risk polyps, particularly those with 1 to 2 small adenomas. Thank you very much for your attention.

colonoscopy screening

surveillance guidelines

colorectal cancer

early adult-onset colorectal cancer

screening recommendations