colorectal cancer staging histology

[silence] my name is david lieberman. i'm the chief of gastroenterologyat oregon health and science university, and i am honoredto participate in this effort by the centersfor disease control and prevention to improve the qualityof colorectal cancer screening. for those of you who do not know me, i am a past president of the americansociety for gastrointestinal endoscopy and a current memberof the governing board

of the american gastroenterologicalassociation, or the aga. i have been a participant in the national colorectalcancer roundtable for many years. i served as chair of the multisociety task forceon colorectal cancer for six years and participated in the development of colorectal cancer screeningand surveillance guidelines. my research has focusedon colorectal cancer screening, surveillance, and quality.

we now have compelling evidencethat colon cancer screening works. it reduces the incidenceand mortality of colorectal cancer but only if it's performed with high quality. this slide presentationwill discuss the current guidelines and recommendationsfor colorectal cancer screening and emphasize importantelements of quality. we hope that these slidesand the various links that we provideto primary-source information will be of value to youin your clinical practice

and provide tools that will help you optimize colon cancer screeningwith your patients. this is going to bea two-part presentation. each of the presentationswill have links to other documents, including additional slidesand source documents that will provideadditional information about guidelines and clinicalpractice recommendations. so we encourage youto use these links, and we'll demonstratesome of these links

during the courseof the presentation. i want to acknowledgethe work of many people who participated in this effort,including gastroenterologists, public health experts,and primary care physicians who all participatedin the development of this course. so to begin, we have evidence now that colon cancer screening works,that it saves lives. we know that screeningis a complex process that achievesits maximum benefit for the patient

when all stepsare implemented appropriately, and we knowthat there are some problems with screening implementationthat have been well documented in the medical literaturefor each of the screening options. so, for example, what are someof these implementation problems? well, with colonoscopy, we know that sometimespolyps are not detected. sometimes a complete examto the cecum is not achieved. the bowel prep may be suboptimal.

the colonoscopy reportmay be missing key elements that would help guide future management. the recommendations for screeningand surveillance intervals that are made after proceduresare sometimes not consistent with practice guidelines,and some endoscopists do not monitor their performance,so they're really not aware when they are not meetingquality standards. there are also implementation problems with the fecal occultblood testing programs.

first, sometimes the testsare just not offered as a good optionfor average-risk individuals. patient preferences for fecal testingare not taken into account. some physicians still use teststhat are no longer recommended-- the old guaiac-based test. some individuals performin-office rectal exams and use thatas their primary screening test, and that is really not a substitutefor in-home screening. and most important,fecal occult blood testing

is a program which involveshaving a colonoscopy if the test is positive,and if that's not done, it's going to impactthe effectiveness of the program, and if the test is negative,exams need to be repeated annually. so these are elementsof implementation that are key to achieving a high-qualityfecal occult blood test program. the goal of this presentationis to improve screening quality by providing up-to-date guidance

on ways to optimizethe screening process with a strong emphasis on the areaswhere current practices may fall short. upon completion of this course, the learner should be ableto recommend the appropriate testing for each patientconsistent with the guidelines for screening and surveillancefor different populations and recognize high-risk groups, understand ways to achievea good bowel preparation, identify the elements requiredfor a complete colonoscopy report

that will be a strong communication toolto primary care providers, and explain which quality indicatorsshould be monitored to improve colonoscopy performance. we know that screening works but that many eligible patientsare not being screened. with this in mind,the national colorectal cancer roundtable has proposed a goal of screeningmore than 80% of individuals by 2018. more than 150 organizations have signeda pledge to help achieve this goal. this goal should be achieved

with attention to the qualityof examinations and testing performed. this presentation is going to focuson providing high-quality testing for those who are screened. the topics we're goingto be covering in part 1 will include colorectal cancer,some information about colorectal cancer and the value of screening,and we will review some of the screeningand surveillance guidelines: who should receive screening,how they should get it, and when and which groupsneed to be stratified

as higher-risk individuals. in part 2,we will talk about colonoscopy and ensuring that the performanceof colonoscopy is appropriate, the importanceof a good bowel prep, the importanceof complete documentation of the colonoscopy results,and recommending appropriate follow-up and the need to perform and improvethe quality of colonoscopy. so to begin with part 1,a few facts about colorectal cancer. in 2011, there were morethan 135,000 new cases

and over 50,000 deaths due to colorectal cancerin the united states. we have a link to the centersfor disease control web site which provides somecolon cancer screening statistics, and you'll see that,if you go to the site, that you can look for information on colon cancer ratesby race and ethnicity. you can look at the rates of cancerand screening in your state. you can look at risk according to age,and you can look at trends over time.

so there is a wealthof information here, and i encourage youto use these links as shown here to further investigate this subject. as i mentioned, colon cancerremains the second-leading cause of cancer death overall after lung cancer, and we have evidence that it can beprevented or detected through screening. the good news about colon canceris that both the incidence and mortality have been declining in the united states so that over the ten-year periodbetween 2000 and 2010,

there was a 30% decreasein both incidence and mortality among adults age 50 and older. so this is exciting news,and we believe that some portion of this decreasehas been directly attributed to increased rates of screeningin the united states. hence, screening becomesan important element of trying to further reduceincidence and mortality from this cancer. most colon cancers develop over time from preexisting adenomasor serrated polyps.

these polyps are very common,and it's estimated that 30% to 50% of us will develop adenomas in our lifetime. most do not progress to cancer,but some acquire additional mutations, become larger,develop more serious histologic changes such as villous histologyor high-grade dysplasia, and in those cases, there is a higher riskof progression to cancer. the estimate of polyp dwell timefor a small polyp to developing into an invasive canceris at least ten years. so this process takes a long timein most individuals.

we have learned that screeningcan impact this natural history in a couple of important ways. first, that if we can detect and remove significantcancer precursor lesions, adenomatous polyps,that we can decrease both incidence and mortalityof colorectal cancer. if we can detect early-stage cancerthat is amenable to treatment, then we can also decrease mortality. so screening offers ustwo exciting opportunities

for reducing mortalityfrom colorectal cancer. screening for colorectal cancerhas been strongly urged by the united statespreventive services task force, which is an expert panelthat produces guidelines related to screening and prevention. this is a group that advises congressand the centers for medicare and medicaid. they've strongly recommendedcolorectal cancer screening for all adults beginning at age 50until at least age 75 with a grade a recommendation,

and what they meanby a grade a recommendation is that there is high certaintythat the net benefit is substantial and substantially outweighs the risk. therefore, based on this recommendation, all practices should be offeringand providing this service. let's talk about some of the risk factorsthat one should consider when deciding to screenan individual patient. so we need to knowwhat the risk level is, what the prior screeningand surveillance history is,

the age and comorbidities,and patient preferences should be weighedinto the decision making. we understand that thereare different levels of risk. the most common group is average risk, and i want to emphasizethat average risk is not low risk, that an average-risk individualwith no other risk factors has about a one in twenty chance ofdeveloping colon cancer in their lifetime. so, therefore, screening is recommended for so-called average riskbecause they are not low risk.

the higher-risk individuals are thosethat have a family history of colon cancer or large adenomas in a first-degree relativeor colon cancer in other relatives, and first-degree relatives are father,mother, sister, brother, or child. it's estimated that the riskof developing colon cancer with this history may double, so that if average riskis about a 5% lifetime risk, for those with a family history,the risk may be 10%. also, patients that havea personal history of adenomas in the pastor certain serrated polyps or cancer

are at risk to develop these lesions again,and they are also at increased risk. at higher risk are individuals that havechronic inflammatory bowel disease. that would be patients with chroniculcerative colitis or crohn's colitis. it's thought that inflammation of the bowel may induce mutationsin the cells of the bowel that could leadto the development of cancer. and so these individualsneed more intensive follow-up beginning at about eight yearsafter the onset of their disease. the very highest-risk groups

are those that havesuspected genetic syndromes. that would be familial polyposis or hereditary nonpolyposiscolorectal cancer, otherwise known as lynch syndrome. and these patientshave extremely high risk of developing cancer at a very young age. the suspicion for these familiesshould be if there is any family member with colon cancer before age 50, we should at least thinkabout the possibility

that this could be an inherited syndrome and take a very careful historyof all family members in that kindred to determine if they needto be referred for genetic counseling. so let's talk about screeningin average-risk individuals, and i'm going to pose a few questions for you to think aboutas we go into this discussion. first, what is the bestcolorectal cancer screening test for average-risk subjects? second, when shouldan average-risk patient

with a normal colonoscopybe screened next after they've had a normal exam? and at what age should patientsno longer be screened? so we'll try to addresssome of these questions. in 2016 the united states preventiveservices task force issued new guidelines and recommendationsfor average risk screening. they included multiple screeningstrategies with different levels of evidence to supporttheir effectiveness. they point out that each strategy hassome advantages and some limitations

and there was no empiric data thatdemonstrated that any one of those strategies would provide a greaternet benefit than the other. the primary goal of this newrecommendation is to maximize the number of individuals whoget screened. the screening tests, the specific tests,are outlined on the next slide. there are stool-basedtests which include a highly sensitive guaiac fecal occultblood test performed every year, a fecal immunochemical test, or fit,which is performed every year, and a multi-targeted dna testwhich includes a stool dna

and fit which can be performed everyone year or every three years. there are several visualization testswhich enable visualization of the colon, colonoscopy performedevery ten years, ct colonography performedevery five years, flexible sigmoidoscopy, alone,performed every five years and flexible sigmoidoscopywith the fit test. the flexible sig is performedevery ten years, the fit test is performed annually. we will highlight the two new teststhat were included in this list

since the 2008 guideline. the first of those tests is themulti-targeted stool dna test, which includes a fecalimmunochemical test and stool dna. this has a higher single testcancer detection rate, and polyp detection ratethan fit alone. the test identifies several keymutations that are associated with colorectal cancer neoplasia andcan also detect blood in the stool. the key features of this test is thatit does appear to be more sensitive for detection of cancer than fit alone,but it results in a higher rate of

false positive tests, and therefore,more colonoscopies would be performed if patients had colonoscopy for a positive test. there is insufficient evidence aboutthe follow up of a positive stool dna test and a negativecolonoscopy. it's conceivable that patientscould have neoplasia in their colon that might not havebeen detected with colonoscopy, and that could lead to overlyintensive surveillance due to these concerns, aftera negative colonoscopy. currently, medicare reimburses the multi-targeted stool dna test every three years.

the second new test introduced by thepreventive services task force was ct colonography. this has beenaround for a long time. it's a ct scan which can be rendered intwo dimensional or three dimensional images. it requires a very thorough bowelprep prior to the procedure, so that there will be no confusionbetween stool versus polyps. it's quite sensitive for polyps,detection of polyps greater than six millimeters,and for detection of cancer. when ct scans are performed of theabdomen there are maybe incidental extra-colonic findings thatare discovered.

but most do not requireadditional evaluation in average riskasymptomatic individuals. however, these extra-colonicfindings do have some potential for both benefit and harm. it's possible to detect occultlesions elsewhere in the abdomen, but there is also, it's also possibleto detect incidental findings that could lead to over diagnosis, overtreatment and potential harm to patients. ideally, the facility performingct colonography should have the capacity to perform same day colonoscopy whenpolyps are discovered

so that patients do not have togo through a second bowel prep. as of july 2016, this procedure is not yetcovered for screening by medicare, but coverage is being reconsidered. it is currently covered for screeningby some private insurers. when should screening beginand when should it end? well, the guidelines strongly suggest that most adultsbetween the ages of 50 and 75 should be offered colon cancer screening. in the elderly,screening may be associated

with increased riskand decreased benefit, and so the u.s. preventiveservices task force has suggested that for individuals age 76 to 85that the decision to continue screening should be made on case-by-case basis, that if patients have had a prior historyof adequate screening that they may not needto have further screening. however, if they've not hadup-to-date screening, then they may benefitfrom more screening provided that they have a life expectancyof at least five to ten years

and would, therefore,be likely to benefit from screening. there's a strong recommendation not toscreen individuals after the age of 85, and that is because the riskbegins to strongly outweigh any benefit after that age group. there's some controversyabout special groups and when screening should be initiated. so one of these groupsare african americans. so we understand that african americanshave a higher risk of colorectal cancer and have a higher risk of deathfrom colorectal cancer,

and some have suggested that, perhaps,screening should begin at a younger age for this higher-risk group. however, the rationaleagainst performing early screening is that most of the colorectalcancer cases in african americans still occur after age 60,as they do in caucasians, that the prevalence of large polypsgreater than nine millimeters is similar for whitesand african americans before age 50, that there is really no evidence that supports the effectivenessof early screening,

and, in fact, there's some modelingthat has suggested that by increasing screening ratesby 10% over the age of 50 that this may actually be more effective than initiation of screeningat a younger age. you'll see that the guidelines do vary. the u.s. preventive services task force recommends beginning screeningat age 50 for african americans. other groups have optedto recommend a younger age, and the coveragefor this type of screening varies

depending on the stateand for insurance companies. our expert consensus,at least at this time, is to begin screening at age 50for african americans but to really intensify that screening effortbecause this is such a high-risk group. there are also individualsthat should not be screened, and these are individualsthat have limited life expectancy and severe comorbiditiesthat would increase the risk of screening so that if the life expectancyis less than five years for really any reason,we do not recommend screening,

and for patientsthat have high-risk conditions because this is an elective procedure, we recommend that screeningbe delayed or not be performed if life expectancyis going to be less than five years. let's talk a little bit about some groupsthat have higher risk of colorectal cancer. so the most common groupare those that have a family history. that would be a first-degree relative--father, mother, sister, brother, child-- that has a history of colorectal canceror large adenomas. here, the guidelines distinguishbetween the age of the family member.

so that if the index family memberthat had cancer developed cancer after age 60, the recommendation is to begin screening with any of the recommendedtests at age 40 and to repeat at the usual intervalsfor those individuals. however, if the family memberdeveloped cancer before age 60 or if two or more first-degree relativesare diagnosed at any age, this represents a higher-risk family, and it's recommended that colonoscopybe the preferred form of screening

and that colonoscopy screeningbegin at age 40 or ten years younger than the youngest--than the index case in the family and then should be performedevery five years instead of every ten years, and this is in recognitionthat this represents a higher-risk family. so a few more questions to think about. what is the recommendedsurveillance interval to the next colonoscopyfor a patient that has a polyp, a seven millimeter tubular adenoma? and what is the recommendedsurveillance interval

for a patientthat has three small adenomas? so we'll try to address these questions about surveillance after screeningin this next set of slides. so guidelines have been developedto guide physicians based on the evidence, and there's a link to this guidelinethat i'd like to show you that specifies some of the evidence. and this will give you an exampleof going to a source document. this is a paperthat was published in 2012 outlining the colonoscopysurveillance guidelines

after screening had been performedand reviews all of the evidence. so i, again, encourage youto use these links, which will provideadditional information. in this paper, we distinguishbetween several levels of risk. first are individuals that were foundto have low-risk adenomas, which are defined as having oneor two tubular adenomas less than ten millimeters. this represents a very low-risk group. the recommendation is to performcolonoscopy in five or ten years

with most of the evidence now leaningtowards the longer interval of ten years, provided that the baseline examwas a complete exam to the cecum and had a good bowel prep. each of these recommendationsis really contingent on the assumptionthat the baseline exam was complete and that the prep was adequate and that all visible polypswere completely removed. the next category are patientsthat have high-risk adenomas. that would be three or more adenomasor adenomas greater than one centimeter

with villous histologyor high-grade dysplasia. these are patients that we knoware more likely to develop additional high-risk adenomas in the futureand have a higher risk of cancer. these individuals shouldhave surveillance at a three-year interval. for those few patients that have morethan ten adenomas on their baseline exam, the recommendation is to go backin a shorter interval to remove any remaining polyps and to think about whether this patientmight have one of the polyposis syndromes. and, finally, if a patient has any adenoma

that was removed in a piecemeal fashionor possibly incomplete excision, that person should haveanother colonoscopy in the next two to six monthsto reinspect that site and confirm that allneoplastic tissue was removed on the baseline examination. we have some new informationabout what to do after that first surveillance examination. so patients that had a baselinecolonoscopy for screening, had a surveillanceexamination for polyps--

what do you do after that? and what this slide highlightsis a relatively simple algorithm for follow-up of these individuals. if the patient had a low-risk adenomaon their baseline examination and has no adenoma on theirfollow-up surveillance examination. they are low-risk and can havetheir next surveillance exam at ten years, which would be the sameas a screening examination. conversely, if that patient was foundto have a high-risk adenoma on the surveillance examination,then they should revert back

to a shorter three-year intervalfor surveillance. in the next row, you see patients that have high-risk adenomason their baseline examination. the evidence would suggestthat this remains a higher-risk individual, and therefore, the follow-upin those individuals should range between three and five years, depending on what is foundon the surveillance examination. well, what about serrated adenomas? many of you have heardabout serrated polyps.

do they ever develop into cancer, and what is the recommendedsurveillance for these lesions? first of all, what are serrated polyps? well, these are lesions, polyps,that are characterized histologically by having a serratedor saw-toothed appearance of the crypts in the epithelium. in the past, most of these lesionswere called hyperplastic polyps because they have an appearancethat is similar to hyperplastic polyps and most do not havecytological dysplasia,

which is a characteristicof hyperplastic polyps. and they were thought to havelittle or no malignant potential. more recently, though,we've learned that a subset of patients with serrated lesions may be a precursor for colorectal cancerin as many as 20% or 30% of lesions. these are most commonlyfound in the proximal colon, and they have certaingenetic characteristics that seem to be associatedwith a higher risk. so as we thinkabout the two types of polyps

that can develop into cancer, one are polyps that go through the traditionaladenoma-carcinoma pathway, which starts with the developmentof an adenoma. there are additional genetic mutationsthat lead to the development of cancer. in the serrated polyp pathway,we believe that this may start as a hyperplastic polyp,that additional mutations may occur, and then there's probably a criticalstep in here in the middle showing that if a serrated polypdevelops cytological dysplasia,

that these patients may have silencingof an important mismatch repair gene that can leadto the development of cancer, and so we believe thatthat is the most likely pathway that these lesions may follow. so these patientscan develop cancers, and understanding the natural historyof these lesions has been troublesomefor two important reasons. first, these lesions are very difficultto detect at endoscopy. they're often very flat.

they often have the same coloras the surrounding mucosa with very indistinct edges. they're often covered with adherent mucusthat obscures the vascular pattern and makes it difficult to see these lesions. so these lesions are probablyoften missed at endoscopy. the second problemwith understanding the natural history is variability in distinguishing hyperplasticfrom other serrated polyps histologically even among expert pathologistswho disagree. so to understandthe natural history of a lesion,

you really needto be able to detect it accurately and you need to classify it accurately. and those are problemswith serrated polyps, and that's why the understandingof serrated polyps is still evolving, and the current management guidelinesare based on weak evidence. ok, this slide discussesthe surveillance of patients with serrated polypsat a prior colonoscopy. for patients that havehyperplastic polyps less than ten millimetersin the rectum or sigmoid,

it's a very low-risk group. they can be rescreened in ten years with any of the recommendedscreening options. for those individualsthat have small hyperplastic polyps proximal to the sigmoid colonless than six millimeters, the recommendation is to performcolonoscopy in about ten years. for those that have lesionsgreater than five millimeters, the recommendation is to performcolonoscopy at five years based on very weak evidence.

and for thosethat have serrated polyps less than ten millimetersin the proximal colon, the recommendation is to docolonoscopy in five years. the group that i think should be highlightedthat i want you to remember are those patientsthat have serrated polyps that are either greater than ten millimetersor have cytological dysplasia. we believe that this may representa higher-risk individual and should be managed like thosewith classic high-risk adenomas and have follow-upcolonoscopy in three years.

and for the unusual patientsthat have serrated polyposis, which are many hyperplastic polyps, some of which are greater thanten millimeters, in their colon, they should have colonoscopyat one-year intervals until all those polyps have been removed. the next slide talksabout the surveillance of patients that have had cancer resected. so these are patientsthat have whatever it takes to develop colorectal cancer eithergenetically or environmentally or lifestyle,

and therefore, they are at riskto develop recurrent cancers. so for those that hadcolon or rectal cancer, the next examinationshould be within six months after their surgical resection if they were not able to have a completebowel examination prior to surgery. this could be dueto an obstructive cancer that precluded performinga complete examination. if they were able to havea preoperative complete examination, then they should have their follow-upat one year after the curative resection

and then every threeto five years thereafter. a possible exception to thisare patients that have rectal cancer, and the concern about rectal canceris that there is a higher risk of recurrences at the anastomosis,and for that reason, many experts recommendthat these individuals have sigmoidoscopiesto inspect that anastomosis every three to six months, possibly with rectal ultrasound as wellover the first two to three years. they should continue, though,to have the full colonoscopy

at the one-year and thenevery three-to-five-year intervals because they're still at risk to developcancers elsewhere in the colon. finally, i'd like to spend a few minutes talking about those patientsthat are at higher risk. so these include patients that havechronic inflammatory bowel disease, including ulcerative colitisand crohn's disease. we recognize that the riskof colorectal cancer begins to increase at about eight yearsafter the onset of disease, possibly related to the inflammation

which causes mutationin the lining of the bowel. for these individuals, colonoscopyis recommended every two years, and there's some new evidencethat suggests that colonoscopy with chromoendoscopy, using dyeslike indigo carmine or methylene blue, may enhance our abilityto detect subtle lesions that may have low-or high-grade dysplasia. so this is something for endoscopiststo consider in their practice, and it's one reasonto consider referral to a center that has expertisein performing surveillance

for inflammatory bowel diseaseand its management. the highest-risk groupsare those that have a genetic syndrome, and those include the patientswith hereditary nonpolyposis colon cancer and familial polyposis. these syndromesshould be suspected in any family who has a relativewith cancer before age 50, in which case complete historyof family members should be obtained, and if suspicion is there,patients should be referred for genetic counseling and testingalong with counseling of the family.

for these individuals, because cancerscan develop at a very young age, testing may begin in late teensand twenties. so it's very importantfor primary care physicians to obtain this historyas part of the initial history and physical that they obtain. thank you for viewing part 1, in which we have tried to focuson the following subjects: who should get screened and when, who is high risk and needsmore intensive screening and surveillance,

and what is the appropriate follow-upof patients after they have had screening. in part 2, we're going to discussissues surrounding colonoscopy and how to ensure that colonoscopyis performed with high quality. i urge you to use the linksprovided in this course to get additional informationfrom some of the source materials. thank you very muchfor participating in this course.

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