Colon Cancer Pathophysiology

[silence] hello, everybody and welcometo part 1 of our program, screening for colorectal cancer:optimizing quality. i'm dr. richard wender. i'm the chief cancer control officer at the american cancer society,and i'm also the chair of the national colorectalcancer roundtable, and i was part of the facultypreparing this program. this is a three-part course.

part 1, which we're going to do right now,is focusing on colorectal cancer, the value of screening, and guidelinesfor both screening and surveillance. part 2 focuses on deliveringhigh-quality stool blood testing as one of the critical options in screening patientsfor colorectal cancer, and part 3 looks at the roleof the primary care provider in delivering high-quality colonoscopy. there's a lot we need to knowabout how to improve the overall quality for patients.

every part of this program includes narratedpresentation with slides, and we have a pdf file of slides that are available to youfor your reference. as we go through these slides, in blue, you will frequentlysee links to other material. these links will take youto external web sites or to full-text article reviews or, in some cases,just some additional slides

that provide informationin greater depth about the topic we're focusing onat that moment. when you click on any of these links,you'll have a number of options for getting backto the main presentation, particularly the slide linksat the end of the slide set. in the bottom right,you'll see a blue "go back." just click on that "go back,"and it will bring you right back into this slide presentationthat has main content. if, however, it takes you to a web siteor a full-text article review,

you'll have to click out,essentially close that link, usually in the top rightof your screen. just close that out,and it will take you right back to the mainslide presentation. this presentationwas developed through the work of an incredible and wonderfulgroup of experts, each of whom is not onlyan expert in their field but dedicated to really makinga big impact on colon cancer as a major public health problemin this nation

and has committed their resourcesto this program. lynn butterly, diane dwyer,david lieberman, marion nadel, mike potter, paul schroy,jean shapiro, as well as myself have comprised the groupwho've worked so hard in putting this together,and as you'll see, this represents expertsfrom gastroenterology, from primary care, and from public healthand epidemiology, bringing togethera number of perspectives

as we've put together this program, focusing on improving qualityof colon cancer screening. to learn more about eachof these individuals, just click on their name,and it'll take you to a link where you can learn a little bit moreabout their background. of even greater importance,this presentation was developed with the amazing supportand dedication of the centers for diseasecontrol and prevention, who's really providedthe overarching framework

and technical advice,expertise, and support in spearheading this project. david lieberman does serveon the scientific advisory board of exact sciences corporation and in the distant past,not recently, did receive some financial supportfor that work. i think it's importantto understand that, ultimately, this work and its conclusions represent the work of the authors

and do not necessarily representthe official positions of the centers for diseasecontrol and prevention or the american cancer society. so we know a lot about screeningfor colorectal cancer, and the main lessonis that it's now proven and accepted without challenge that screening for colorectalcancer is lifesaving, and we're seeing huge progressin reductions in mortality, and we'll go over those data.

but the reality is thatscreening for colon cancer is a complex process, and the only waywe get maximum benefit is when we achieve maximum quality, which means that we implementall of the steps in a high-quality, appropriate way to get the greatest benefitfor our patients. the reality is thatwe know from lots of data that screening implementationis not happening

with uniform high qualityaround the nation, and really the goal of this program is to try to bridgesome of those quality gaps. so what are some of thoseimplementation problems? well, with fecal occult blood testing, we know that there area number of common errors. one, fecal occult blood testing, is sometimesnot being offered at all, even though it's a very good optionfor screening average-risk patients.

we know that patient preferencefor fecal occult blood test is often being ignoredor simply not investigated, and we know that patientpreference matters, and i'll show yousome data about that. we know that some tests,stool tests, are still being usedthat, frankly, are not recommended by any of the current guidelines,and we know that some clinicians are still using in-office tests gathered at the timeof a rectal exam,

not recommendedby any of the guideline groups because the data's clear that it's simplynot sensitive enough. one of the most concerning errors is that patients are gettingabnormal stool tests but are not always receivingthat critical follow-up colonoscopy, and an abnormal stool blood testthat isn't followed by a colonoscopy is not going to save anybody's life,and it's a critical quality gap. finally, fecal occult blood testing

in every caseis recommended every year. it has to be repeated annually,and we know that some patients are just gettingthis test sporadically, and if you only get it sporadically, you will not getthe same mortality benefit that we achieve with annual testing. how about quality gapswith colonoscopy? well, we know thatalthough in some settings, and some endoscopistsare doing a tremendous job

and are meetingall of these quality steps, that the quality is extremelyvariable across the nation. here are some of the issuesthat are present. one, polyps are being missed. we know that polyp detection ratesare quite variable across the nation. we know that the cecumis not always being reached or nearly always being reached, and, again, the cecal intubation ratesvary across the nation. in some cases,bowel preparation is suboptimal,

and we know,through the best standards, using careful patient navigation, it's possible to achievean excellent bowel preparation almost every time. in many instances,the colonoscopy reports are missing some important elements,and in part 3 of this presentation, we're going to go overwhat you should expect to see in a colonoscopy report. we know that recommendationsfor screening and surveillance intervals

are not consistent with guidelines. there's all sortsof variable recommendations that primary care cliniciansare receiving, and even sometimes when the correctrecommendation is received, they're not always being followed. finally, it really is a standard now that endoscopistsmonitor their performance just the way we've learnedwith all quality improvement, and this is not happeningacross the nation,

and that's a real goal--to make sure that all endoscopists use a registryto monitor their performance and they're aware of how they're doingin meeting these quality standards. we have an overarching goal for all three partsof this presentation, and that is to improve screening qualityby providing up-to-date guidance on the ways to optimizethe screening process. and we're going toparticularly emphasize the areas where our current practiceoccasionally falls short

of these very high quality standards. at the end of this course,we're confident that our learners will be able to explainthe importance of offering both stool blood testingand colonoscopy as options for screening, that they'll be ableto recommend appropriate testing for each patientthat's both consistent with not onlythe screening guidelines but also the surveillance guidelines

for people who havean abnormal initial screen, and that you'll be able to do this for different populationsubgroups based on risk. third, you'll be ableto identify the elements of a high-qualitystool blood testing program and, even more importantly,be ready and prepared to implement these high qualitystandards in your practice. and finally,you'll be able to identify the characteristics of a high-qualitycolonoscopy service,

and you'll be able to takesome important steps to improve the qualityof colonoscopy offered for your patients. many of you may have heardabout this very bold goal that has been set nationally to achieve 80% colon cancerscreening rates by the end of 2018. we know that many eligible patients are not being screened,and these include people that you've seenin your own practice,

people who you mayhave had the opportunity to recommend a screen, but you didn't realizethat they weren't up to date, or you gave them a recommendation,but they didn't follow it. so we're going to try to reallyhelp improve those rates. this "80 by '18" goal was established by the national colorectalcancer roundtable in 2013, and since that pointin november of 2013, the momentum for this nationalpublic health challenge

has been extraordinary. more than 150 organizationshave signed a pledge to dedicate their resources to achieve this wonderfulpublic health goal, but the reality is,achieving 80% alone will not get the mortality benefitthat we'd like it to get unless high qualitystandards are met through every stepin the screening process. so we're not just interestedin 80 by '18.

we're interested in 80 by '18with high quality. that will get usthe maximal reduction in both incidence and mortalityfor colorectal cancer. that's our focus of this presentation;it's quality. so, what are we going to coverin this part of the presentation? well, we're going to cover colon cancerand the value of screening, and we're going to talkabout the screening and surveillance guidelines:who should be screened, how they should be screened,and when they should be screened.

we're going to focus on the importance of stratifying by risk:average risk, increased risk based on familyhistory and personal history, and finally, on high-and highest-risk patients for whom the recommendations,of course, are very, very different,but are extraordinarily important. so let's begin by talkingabout colorectal cancer and the value of screening. colon cancer isa major public health problem.

in 2011, about 135,000 new casesof colon cancer were diagnosed, and just under 52,000 individuals in the united statesdied of colon cancer. this makes colon cancerthe second-leading cause of cancer-related death overall, falling just behind lung canceras a cause of cancer-related death. the good news about colon canceris that it can be prevented or it can be detected earlythrough screening, particularly if that'sperformed with high quality.

we're making a lot of progressin the united states. incidence and mortalityhave been declining in the united states for years. in fact, mortality declines in womenstarted in the 1950s. but we've-- more recently,we've seen a substantial drop in the incidence of the disease. in fact, from 2000 to 2010, there was a 30% decreasein incidence

among adults age 50 and older,and there's no doubt that screening has beenan important contributor to the progress we're making in reducing bothincidence and mortality. so we've madea tremendous difference in the united states,but we can still do more, and we can preventmore colon cancer deaths and move to substantiallyreducing colon cancer as a major public health problemthrough high-quality screening.

i think most of you know this,but let's make sure that this link between polypsand the natural history of colon canceris understood by everybody. most cancers of the colonand rectum develop over years from adenomatousor serrated polyps. polyps are very common, and they become more commonas people get older. the reality isthat very few of them actually progress to cancer.

the ones that are more likelyto develop into cancer, though, are larger or they have dysplasiaor villous histology. those are the polyps that have a higher riskof progression to cancer, and you'll see that in oursurveillance guidelines, that these characteristicsof the initial polyp that's removed have some impact on whenwe should do the next test. the reason why we'veestablished these intervals is based on the natural history

of this polyp-to-cancer sequence. the estimate of polyp dwell time from going to being less thana 1-centimeter adenomatous polyp to an invasive canceris at least ten years, and that facthas certainly been important in establishingour screening intervals. we really have two strategiesin colon cancer, which really gives usa tremendous advantage in making public health progress.

when we detect and removeclinically significant polyps, we both decreasethe incidence of the disease, and we decrease mortalityfrom colon cancer, but in addition,high-quality screening can detectearly-stage colorectal cancer, which, when treated appropriately,contributes to a decrease in mortality. i think it's importantthat patients understand that we're not just talking aboutscreening for early cancers. we're talking about screeningfor precancerous polyps,

and if we remove the polyp,we can prevent the cancer. i think that's an appealing prospectfor lots of people who may be reluctantto undergo screening. one of the, really,pieces of good news about colon cancer screeningis that it's universally endorsed. the u.s. preventiveservices task force recommends screeningfor adults beginning at age 50 and continuing until at least age 75, assuming the person's healthy,and we'll go over that.

they gave it an a grade, meaning that there's high certaintythat the net benefit is substantial and, therefore, that this service should be uniformlyprovided or offered. the american cancer society, the multisociety gi task force, and we're going to referto that group guidelines as well, substantially agree. no debate;all of us should be screening

with high quality for colon cancer. ok, let's move to talkingabout our screening and surveillance guidelines:the who, the how, and the when. i think oneof our most important messages when we talk about this overall areaof who should be screened is that you cannot determinethe right screening test and the right screening interval without establishing the risk categoryfor your patients. so we're going to go overhow you figure out

if your patient's average risk, increased risk,or really at very high risk. you also need to know the patient's screeningand surveillance history. have they been tested before?what was found? and if you don't knowthe answers to that, it's important to find outbecause that has an impact on what test should be doneand when it should next be done. obviously, age--very importantdeterminant of risk

and when you startand stop screening. you need to know somethingabout the patient's health. comorbidities have a big impact on how long we screen patientsand what tests we use, particularly whether we screen at all, and we are going to emphasizethis very important factor of understanding patient preferences, which can have a big impacton increasing the likelihood that your patient actuallyparticipates in screening.

so here are the risk categories. bear with me;let's go through each one. what determinesif someone's average risk? well, if they fall intothe age range that we talked, 50 to at least 75 years oldand healthy, have no signs or symptomsof colon cancer, and they have noneof the risk factors that we're going to go overin the following bullets here, they're at average risk.

we don't use the term "low risk." that term went away a long time ago. everybody is at riskfor colon cancer. they're just at average risk,and therefore, we can use tests that are appropriatefor patients at average risk. how about increased risk? well, increased risk is the patientwith a family history of colon cancer or adenomas, and we often don't ask about that,in a first-degree relative

or colon cancer in twosecond-degree relatives. so, again, you needto do a little bit more extensive family historyto determine this category. if the patient has a personalhistory of adenomas as well as certain serrated polyps or if they have a personalhistory of colon cancer, they're in an increased-risk group. high risk--that's patientswith inflammatory bowel disease such as chronic ulcerativecolitis or crohn's colitis.

those patientsare at quite high risk, and i'll give you some guidanceabout how to manage those patients. and finally,patients at highest risk, and those are individualswith confirmed or suspected genetic syndromeslike familial adenomatous polyposis or hereditary nonpolyposiscolon cancer syndrome. those really definevery high-risk patients. i'm going to use the term "surveillance"during this presentation. i already have,and i will again.

i just want to emphasizethat the term "surveillance" is used for testing patients with a personal historyof colorectal cancer/adenoma, certain serrated polyps, or cancer. so they're still asymptomatic. they've never-- but we're doing testingat a regular interval. it differs from diagnostic testing, which is required for patientswith signs or symptoms.

screening and surveillance,patients with no symptoms, patients who have symptomsthat need to be explored are getting diagnostic testing. all right, let's talk about guidelines for screening patientsat average risk for colon cancer, and a number of timesduring this presentation, i'm going to hit you with a pop quiz. so i'll trust you to reallykind of get your minds working and see what you thinkthe answers are to these questions.

so here's question one. what's the best colon cancerscreening test for average-risk patients? number two, when shouldan average-risk patient with a normal colonoscopybe screened next? and number three,at what age should patients no longer be screened at all? all right, got your answers down? let's forge ahead,and we'll go over each of them.

in 2016, the united statespreventive services task force updated their guidelineto screen individuals at average risk for colon cancerand included some new screening options that were not part of theirprevious update in 2008. there were also some new messagesthat are important to emphasize. first, they emphasize thatmultiple screening strategies are available. and they highlightedthat these different strategies each have a varying level of evidenceto support their effectiveness. they also talk aboutthe advantages and limitations

of each of the screening tests to help clinicians and patientsbetter understand their choices. but i think if there’s one importantmessage from this new guideline, it’s really that there are noempirical data available that demonstrate that any one of the strategiesprovides a greater net benefit than any of the others, and as a result the task forcequite appropriately emphasized that the goal of this new guidelineis to maximize the number of people who are screened.

there’s a test out therethat’s right for everybody and we now have a somewhat larger menu, and overall, have a quite robust menuof screening options to help patients find the testthat’s right for them. here is the list of the new,both the old and now the two new screening strategies that havebeen added to the task force guideline. they divide them into stool-based testsand visualization tests, but i want to emphasize thatthis is just an organizational principle, this is not a prioritizationand, in fact,

the task force does not put any one testas a higher priority over any other. all of these are quite appropriatescreening strategies. i do think though thatevery office has the responsibility to be able to offer at least onestool-based strategy, and every office has to be ableto offer colonoscopy, because colonoscopy, in addition to beingan excellent primary screening strategy, is the final common pathwayto evaluate any other test that was found to be abnormalon initial screen. in the second part of this presentationwe’ll go into greater depth

about how to implementa good stool-based testing strategy. and in the third partwe’ll talk about quality colonoscopy and visualization tests. but in this part of the presentationi just want to go through the menu and highlight the twonew strategies that have been added. so, the task forcecontinues to recommend highly sensitive guaiac fobtas an annual testing option, continues to offer fecalimmunochemical test, or recommend it, every year as a good screening option

but has now addeda new stool-based strategy and that’s a test that combinesfecal immunochemical test with a stool dna test.it’s done on a single sample and it’s recommended every oneor three years. the reason why there’s thisoption about interval is that the researchhas not yet been conducted to compare the value of annual testingto every three year testing, and in fact the task forcespecifically called for that research to be conducted.

in visualization tests, of course,colonoscopy every ten years, a vital and important option, but now the new optionthat’s been added is ct colonographythat’s recommended every five years, flexible sigmoidoscopy every five yearsstill recommended, and flexible sig every ten yearscombined with an annual fecal immunochemical testis also a recommended strategy. any one of these approachesconstitutes high-quality screening. let’s go into some depthabout the two new tests

that have been added to the menu. the first is the multi-targetedstool dna test, or fit-dna. just as the test namewould suggest, this combines fecal immunochemical testslooking for microscopic blood, with a stool dna test. right now there’s only one brandavailable, that’s called cologuard and that’s why we mentioned it here. in a trial where everyonehad colonoscopy, looking at sensitivity and specificitycompared to fit alone,

the company manufacturers foundhigher single-test cancer and polyp detectionthan fit alone. so in fact, the fit-dnais a more sensitive test when you just look at a singleperformance, a one-time performance. the flip side is thatthe specificity of the test was actually somewhat lower thanfecal immunochemical testing alone, so that results in a bit morefalse positive results and the greater need for thenumber of diagnostic colonoscopies. one of the concernsthat’s been raised about this test,

still a good research question,an important one, is that if a patient tests positiveon the fit-dna, and that leads to colonoscopywhich is negative, there may be lingering concernsabout the meaning of the abnormal dna part of the test. and there’s some worry that thislevel of concern may lead to overly intense surveillance. for example, doing a colonoscopyevery year, which would be far more intensethan we would recommend,

for some other approachin following up an abnormal stool test like an abnormal fit. right now medicare is reimbursingfor this test every three years, so the annual is not reimbursed todayand would need more research to see if it that would be covered. the second test that was addedis ct colonography. you may know this test as so-called“virtual colonoscopy,” but i like the real name. i’ve always called it ct colonographybecause it’s not a virtual experience. the patient requires a bowel preparation,

there is a tube in the rectumwith air insufflation. although it’s certainly a well tolerated test,it is a real test it’s just not a virtual test in any way,so full bowel prep needed. the good news about this test is thatit’s quite sensitive for polyps that are 6 millimeters or greaterand sensitive for cancers, and that’s reallythe compelling reason why this test was added to the menu. one of the concerns that’s been raisedabout ct colonography is that when you do a radiology study,as you would expect,

you find some things, some abnormalities,outside of the colon itself. these are so-called“incidental extra-colonic findings,” ecfs, and these are actually relatively common. now the good news is most of thesedo not require any additional evaluation, but some of them you will seein the report, the request, or the recommendationfor further evaluation. today, we actually havequite limited evidence on the balance of benefits and harmsin evaluating these extra-colonic findings. there certainly is the potentialfor benefit, for example,

in finding a previously unsuspectedabdominal aortic aneurysm or an extra-colonic cancer, but there’s also the risk of harm,such as overdiagnosis and overtreatment. for example, a kidney massor an adrenal mass that never would have botheredthe patient or been apparent clinically, had it not been foundduring the ct colonography. so there’s someunanswered questions here. the ideal way to performct colonography, and really the state of the art,i think, for performing this,

is that a facility shouldhave the capacity to provide a colonoscopy on thesame day as the ct colonography, in order to remove any polypsthat were found in the radiology study. doing it this way means thatthe patient only needs one prep. if you have to send the patient homeand schedule a colonoscopy, the patient has to do another prepand come back. one: not all of themare going to do that and certainly it’s a barrierto having patients choose this option, the need to potentially do two preps.

as of july 2016, this test,ct colonography, is actually not coveredby medicare for screening, but coverage is being reconsideredso you have to check the cms web site for updates. the good news is that it is alreadycurrently covered for screening by some private insurers, andwith it being added to the uspstf menu, it’s likely that coverageby private insurers will increase. as we focus on average risk,let's begin first talking about the ages of the individualswho should be screened.

so average risk includesmost adults age 50 to 75. the adults who are not included are those individualswho have advanced morbidity, and we will talk about themin just a few moments, but for healthy 50- to 75-year-olds,they should be offered screening, and this is grade a. this service should be offeredand, whenever possible, encouraged and providedto those individuals. how about screening older individuals?

quite clearly, as people age,the likelihood of benefit from a screening test declines,and the risk of harms increases, and for that reason,the task force used modeling data to come upwith a grade c recommendation. what grade c meansis that this service should be offered or provided for selected patientsdepending on individual circumstances but should not be routinely recommendedfor everybody in this age group. so for individuals 76 to 85,what we're focusing on are basically healthy individuals,

particularly those who are notup-to-date with screening. if somebody reaches age 76, they've been recently screened,and they're normal, the value of additional screeningbeyond that age is actually very, very lowand probably should not be offered. but for those individualswho are not up-to-date with screening and who are healthy,there may well be value. in fact, there are a numberof modeling studies suggesting value of screeningthese individuals

because colon canceractually does represent a substantial risk of deathif this person is not screened. so for the individuals not up-to-date,continue screening as long as the life expectancyis at least five to ten years, so, again, mainly focusingon healthy older individuals. once a person reaches age 85, there is uniform agreementthrough all the modeling data that the likelihood of harm substantially outweighsthe likelihood of benefit,

and the recommendationby the task force is grade d. this test should be discouraged, and we should notbe recommending screening for individuals over 85,even if they're very healthy. one of the areas of debate has been when to start screeningafrican-american patients. why has this come up? well, there is some rationalefor earlier screening because there is higher age-specific ratesof colon cancer among african americans,

so that really has beenthe basis for some organizations considering beginning screening earlier,but it's important to understand that there is a rationaleagainst earlier screening. most colon cancer casesin african americans occur after age 60, just the way they doin non-african americans. the prevalence of polypsgreater than 9 millimeters is similar for whitesand african americans, and frankly,there is no definitive evidence through a trial looking at mortality

supporting the effectivenessof earlier screening. i think perhaps the mostimportant point of all is that, when you look at how we deployour limited resources in health care, increasing screening ratesby greater than 10% among african americanswho are already over age 50 is actually a more effectiveuse of resources and a more effective strategythan earlier screening. now, as i mentioned, guidelines vary, that both the task forceand the acs/multisociety recommendation

recommend beginning screeningat age 50, but two gastrointestinal groups actually recommend beginning at 45, and one small guidelinefrom the american college of physicians suggested that we should begin at 40. coverage for earlier screening varies,and most coverage will begin at 50, and that's what most of the laws require, mandatory coverage beginning at 50,so coverage might be an issue in that you mighthave to appeal to get,

for example, colonoscopycovered at a younger age. you'll see that we puta recommendation up here, and that's to begin screeningat age 50, but i want to emphasizethat this is the recommendation coming from the facultywho prepared this program, and a lot of us have servedon a variety of these guideline groups and have looked at the data,but i do want to be clear that this is our expert opinionthat recommend that screening should begin at 50,

and as i mentioned,we don't have a definitive trial. ok, next pop quiz. how should a patientwith class iii heart failure be screened? ok, you have your answer. well, the reality is,this patient should not be screened. patients with severecomorbidities have two factors that diminishesthe net value of screening. one, they may not live as longto get the benefits of a polyp removal, which might take 12, 13 yearsbefore it posed a risk of death,

so less likely to benefit,but, of course, they're at substantiallyhigher risk of harm. so if the estimated life expectancy is less than five years,such as someone who already has a formof metastatic cancer, alzheimer's disease, or stage iii--class iii or iv heart failure, these patients should not be screened because their life expectancyis not long enough. there are other patientswho shouldn't be screened

simply due to the risk. patients with high-risk conditionssuch as neutropenia, unstable angina, or a high risk for operative complicationsshould not be screened at all. so it's important,and as primary care clinicians, we're the oneswho are in the right position to do this, that we take into account the underlyinghealth status of our patients. as a family doc, i understand that some of these conversationscan be a little bit difficult. it might be hard to tell somebody,

well, you don't need to be screenedbecause of limited life expectancy, but remember, you're doingmore harm than good if you proceed with screening. ok, what about-- we've talked about patientsat average risk. let's go over screeningand surveillance for patients at increased risk. the way we establishrisk factors--risk category is by taking a personal historyand a family history.

so let's talk first about patientswith a positive family history. this is a little bit complexand hard to remember. so my personal recommendationis that this is something you should print outor have linked to your emr or have on a wall at your deskbecause it can be hard-- or something that you puton your electronic device to remind yourselfabout these intervals, and this is based on a combinationof evidence and expert opinion. i do want to make that clear.

it's hard to do definitive trialsfor each one of these risk categories. so here we go. if a patient has eithercolon cancer or adenomas in a first-degree relative that were diagnosedat age greater than 60 or two second-degree relativeswith colon cancer, they are at an increased risk groupand therefore, moving to the right, they should begin screening earlier,and that should begin at age 40, but importantly, the recommendation

is not necessarily that theybe screened with colonoscopy. they can be screened with anyof the recommended tests that we went over beforefor the average-risk individual. the only difference for this groupis that they begin at 40. so that's if the family historyis for patients over age 60. now, if the patient has eithercolon cancer or adenomas in a first-degree relativebut they were diagnosed before age 60 or two or more first-degree relativesdiagnosed at-- first-degree relatives now--diagnosed at any age

with a family historythat's not suggestive of a genetic syndrome,because that would put them even into a different category, once again,screening should begin earlier, but the age to begin is slightlydifferent than in the group above. it should begin at 40or ten years before the youngest case diagnosed in the family member,whichever one comes first. the other differenceis that for this group, where the family memberswere younger

or two or more first-degree relativeswith cancer at any age, colonoscopyis the only recommended test. so colonoscopy every five yearsstarting at age 40 or ten years before the youngest case in the family was diagnosed,whichever comes first. so as i said,somewhat complex recommendations-- a little hard to remember.it's good to have a helpful resource near your handwhen these patients come up. now, let's talk about surveillance.

there's, again, i think,a lot of misunderstanding about surveillance intervals, and we can make a big differenceby helping advise our patients what makes sense and really meetingwith our colonoscopy team and coming to an agreementthat we're going to follow these evidence-based guidelines. so if a patienthas a low-risk adenoma, one to two tubular adenomasthat were less than 10 millimeters,

the patient should have their nextsurveillance test with colonoscopy, but the interval can be somewhere between fiveand even as long as ten years. so one very small tubular adenoma,negative family history-- a ten-year intervalmay be very appropriate. now, let's talkabout if the initial finding were high-risk adenomasand what would define high risk, so three to ten adenomasthat were small-- less than 10 millimeters--or one or more adenoma

that was large--greater than 10 millimeters-- or one or more adenomawith villous features or one or more adenomawith high-grade dysplasia. the recommendationis now that these patients, again, be screenedonly with colonoscopy-- stool testing's no longer an option--but that it be done in three years. so the high-risk adenomas,colonoscopy in three years. now, what if a high numberof adenomas were found initially, greater than ten adenomas?

these patients should not onlybe screened prior to three years, but these are patients who,in almost every case, you would want to consider whether they have familialadenomatous polyposis or hnpcc and refer to a genetic counselor. finally, occasionally,you'll have a report that says, listen, we didn't get all of this polyp,so this--you know, it's an adenoma, but we didn't get it all,so it's piecemeal or possibly incomplete excision.

this person should go backfor a colonoscopy no later than a six-month interval. they should have another test. one issue that does come up a lot is, you have a patientwho had that initial colonoscopy. let's say an adenoma was foundor more than one. then they have that next test,which was the colonoscopy. what do we do after that? so if the initial findingwas a low-risk adenoma,

in the second box here,the second column is what was foundat the first surveillance. so we're going to startlow-risk adenoma, but the first surveillance found--now found a high-risk adenoma, that patient should havethe next surveillance in three years. if you start low-risk adenomaon the baseline, low-risk adenoma foundon the first surveillance, they should continue to havecolonoscopy every five years. if the first colonoscopyshowed a low-risk adenoma,

the first surveillanceshowed no adenoma, this patient can now go backto being screened at a ten-year interval using colonoscopyas the test, not stool testing. how about if the baseline colonoscopyshowed high-risk adenoma? well, if anotherhigh-risk adenoma is found at the first surveillance,obviously, this patient needs to stay on a very frequent interval;namely, three years, and may even be a candidate, depending on other findings,for genetic referral.

if the first baselineshowed a high-risk adenoma, but the first--i'm sorry--the baseline showed a high-risk adenoma but the first surveillanceshowed a low-risk adenoma, this patient can now goto a five-year interval, but unlike the group above, whose initial findingwas low-risk adenoma, once a patienthas had a high-risk adenoma, they should not be screenedany less frequently than five years. so if the baseline colonoscopyshowed high-risk adenoma,

the first surveillanceno adenoma at all, they should still stayon a five-year interval. this is another, i think,important reference tool to have available nearbywhen you're making these decisions. next, we're going to beginan emerging topic that i know you've heardsomething about, but i think this presentation will help you be more precisein understanding where we are with serrated polyps.

serrated lesionsare characterized histologically by a serrated, saw-toothed appearanceof the crypt epithelium. now, in the past,most serrated lesions were simply calledhyperplastic polyps and were thought to haveno malignant potential, and i'm sure many of youwere practicing at a time where you never sawa pathology report that said "serrated lesion,"but more recently, a subset of serrated lesionshas been identified as the precursor

of as many as 20% to 30%of colon cancers, and many of theseare in the proximal colon. in fact, these are primarily found in the proximal colon,and many of you know that we've not madeas much progress in reducing mortalityfor proximal cancers as we have for distal cancers. let's go over the natural historyof colorectal cancer. i know that most of youare quite familiar

with the adenoma-to-carcinoma pathway beginning with normal mucosa,progressing to small adenoma, some of thosebecoming large adenomas. some of those large adenomaswill develop high-grade dysplasia, at which pointthey are at substantial risk to develop into invasive cancer, and if that is not foundand treated early, metastatic diseaseis the likely consequence. here's our current understandingof the serrated polyp pathway,

again, beginning with normal mucosa. one of the pathologic typesof hyperplastic polyp is the microvesicularhyperplastic polyp, which has the potential todevelop into a sessile serrated polyp initially without dysplasia,but some of those will eventually develop dysplasia, and it's those polyps,the sessile serrated polyps with dysplasia,that now have the potential to becomean invasive serrated cancer,

which has the potentialto be a threat to life through eventuallybecoming metastatic. our knowledge of these pathwaysis still evolving, but i think we do havea much clearer sense today about this serrated polyp pathwaythan we did some years ago. serrated polyps, especiallythe sessile serrated polyps, can be hard to see,and this is not surprising. they can be the same coloras surrounding mucosa, and they often have indistinct edges.

they're nearly always flat or sessile--not surprisingly, tougher to find. it's not unusual that they havea layer of adherent mucus that obscures the vascular pattern. the other reality of this is that there's quitesubstantial variability in distinguishing hyperplasticfrom other serrated polyps with malignant potential,such as the sessile serrated polyp, even among expert pathologists. so we're still in the learning phase,

although we have madeenormous progress in the last five yearsin understanding both the sequence and in what the endoscopistsshould be looking for when they do the colonoscopies, and i have hadmore and more patients where the wonderful groupthat i work with has found and removedthese serrated polyps. many of the guidelinesthat i've given you to date about serrated polypsand the ones i'm about to show you

are really based on weak evidence. we don't have the high-qualityclinical trials that we would needto have high-quality evidence, but i do think they recommenda high-quality expert opinion and are the best guidancewe have today. so let's talkabout surveillance of patients with serrated polypsfound at a prior colonoscopy. now, as i mentioned,all of these guidelines are based on weak evidence.

we just don't havethe trial data available to make reallyhigh-quality recommendations, but i don't want to diminishthe value of these guidelines. this really is the synthesisof very good expert opinion, and it's the best guidance we have based on where we arewith our knowledge today. there's a couple of things that matter:the type of polyp, the size of the polyp,and the location of the polyp. so, once again, this is a resourcethat you should have available to you.

it's really hard to memorize it,but let's go over each recommendation. so if the prior colonoscopyshowed a hyperplastic polyp less than 10 millimeters located distallyin the rectum or the sigmoid, this patient is really felt to beessentially at average risk, not to be at high riskfor a subsequent cancer, and they can be rescreenedin ten years with any screening option because they're essentially consideredto be average risk. the next category, however,is a hyperplastic polyp that's small, less than 5 millimeters,but that's proximal to the sigmoid.

location matters. the current expert-opinion guidance is that these patientsshould be screened in ten years, but they should be screenedwith colonoscopy, not with a stool blood test option. third category,a larger hyperplastic polyp greater than 5 millimetersthat's also proximal to the sigmoid-- the current guidanceis that these patients should be rescreened with colonoscopyin five years, not in ten.

if the initial findingwas a serrated polyp that's small, less than 10 millimeters, with no dysplasia, again,colonoscopy in five years is the appropriate surveillance. next, if it's a serrated polypgreater than 10 millimeters or if dysplasia is found, these patients areat substantially higher risk and should have their nextcolonoscopy in three years. there is a rare but real syndrome

of serrated polyposisor hyperplastic polyposis. these patients will often have more than 20 hyperplastic polypsfound at colonoscopy. it's not somethingthat happens frequently, but you will occasionallyrun into such a patient, and these patients are actuallybelieved to be at quite high risk and should have their nextcolonoscopy in one year. we've provided the links for youto get greater detail about how these expert-opinionguidance statements were arrived at.

next is the patientwho's actually had cancer, and let's talkabout surveillance of patients who've undergonea resection for a cancer. so if the patienthad colon or rectal cancer, the next examinationwould be within six months unless it was completed preoperatively. actually, the preferredapproach for these patients is to essentially clearthe colon preoperatively, assuming that it's possible to do that.

some of these patientshave an obstructing lesion. some of these patients are quite ill, and they cannot havethat pre-op colonoscopy. so if the patient had nothad it done preoperatively, then they need a colonoscopywithin six months. if they did have it cleared,they can have their next colonoscopy one year after curative resection. assuming everything's good, they can then goto a three- to five-year interval.

there is one option that's available for surveillancewith patients with rectal cancer, and that's reallyto identify local recurrence. for patientswho have had rectal cancer, there are a number of optionsto look for local recurrence, including flexible sigmoidoscopy, rigid proctoscopy,or even rectal ultrasound. these can be doneevery three to six months for the first two to three yearsbut may also be considered

in addition to colonoscopic surveillance,as we've described above. the final categoryis screening and surveillance for colon cancer in patientswho are at high or highest risk. i cannot emphasizeenough the importance of communicating to your patients that if they haveinflammatory bowel disease, either chronic ulcerative colitisor crohn's disease-- crohn's colitis--they are at high risk, and they must undergoregular surveillance

for colon canceror premalignant lesions. the reason this is so criticalis that patients who are doing well, who are symptom-free,often make the mistake of thinking that, well, if i'm feeling goodand i'm not having symptoms, i can just letmy colon cancer screening go just like my spouse does. he or she only goes every ten years or only doesthat nice stool blood test, which is easy to do.

in fact, these patientsremain at high risk, and our recommendation is that they actually be referredto a center that has experience with inflammatory bowel diseasesurveillance and management to really come upwith a personalized plan, which i guarantee you will includefrequent surveillance with colonoscopy. finally, patients at highest risk: these are patientswith a family history of or suspected hereditarynonpolyposis colon cancer,

which we usually call hnpcc, or familial adenomatouspolyposis, fap, or some of the other very raresyndromes that are associated with an extraordinarily highrisk of colon cancer. the real key step for usas primary clinicians-- primary care cliniciansis to refer these patients for genetic counselingand consideration of testing. you know, the only waywe're going to find these patients is to obtain a complete family history.

you know, i know that sometimeswe ask patients these questions, and they're not sure about the answer,but if they have some suspicion-- oh, yes, someone had some sortof cancer in their belly, i'd give them a homework assignment of really tracking downsome family members who may have a richer,more complete knowledge of the family. you really don't wantto miss these patients because their risk for colon cancer is,of course, very, very high, and, in fact, we can't waittill they're 40 or 50

to be getting this kindof detailed history because the testing in these patientsoften needs to begin in their late teens or their 20s. so we have to begin quite early to get that really completefamily history and identify these familieswho may have hnpcc or fap, and although particularly hnpccis infrequent, it is not rare. the odds are pretty goodthat each of us at some point in our practiceis going to see a patient or two

who has one of these conditions. so that finishes all the workwe have around the guidelines, about screening recommendationsand surveillance recommendations. thanks for viewing part 1, and in part 2, we're going to goand look at high-quality testing using a stool-based option.