STUDENT VERSION

A Critical Look at Prevention:

Colorectal Cancer

Screening

John Epling, MD, MSEd, FAAFP Mary Applegate, MD, MPH Anna Zendell, PhD, MSW

Elizabeth Whalen, MD

Modified from Cases in Population-Oriented Prevention (C-POP)

prepared by: John W. Epling, MD

Cynthia B. Morrow, MD, MPH Donald A. Cibula, Ph.D.

Preventive Medicine Program SUNY Upstate Medical University

Abstract:Thispreventivemedicineteachingcase,partoftheCasesinPopulation‐OrientedPreventionseries,discussestheconceptsofscreening,prevention,anddiagnostictestevaluationusingtheexampleofcolorectalcancer. Featuresofthecaseincludeahealthpolicyexerciseconcerningcommunityscreeningprogramsandanexerciseinclinicalpreventiondecision‐making.RecommendedReading: Lieberman,DavidA.ScreeningforColorectalCancer.NEnglJMed2009;

361(12):1170‐1187 U.S.PreventiveServicesTaskForce:ScreeningforColorectalCancer:

RecommendationStatement.AnnInternMed2008Nov4;149(9):627‐637 AmericanCancerSociety/USMulti‐societyTaskForceonColorectalCancer/American

CollegeofRadiology(ACS/UMSTF/ACR)ScreeningandSurveillancefortheearlydetectionofcolorectalcancerandadenomatouspolyps,2008:ajointguidelinefromtheAmericanCancerSociety,TheUSMulti‐SocietyTaskForceonColorectalCancer,andtheAmericanCollegeofRadiology.CACancerJClin2008May‐Jun;58(3):130‐160.

Objectives:Attheendofthecase,thestudentwillbeableto: Describetheappropriateconditionsforadoptingcolorectalscreeningprogramsintermsof

characteristicsofthedisease,thepatientandthescreeningtest. Describetheappropriatestudydesigntoevaluatetheeffectivenessofascreeningprogram

anddiscussthecommonbiasesencounteredinscreeningprogramresearch. Calculatethecharacteristicsofdiagnostictests:sensitivity,specificityandpositiveand

negativepredictivevalues. Evaluatescreeningtestsintermsoftheirvalidity,resultsandgeneralizability. Discusstheconceptsofprimaryandsecondarypreventionastheyrelatetocommonclinical

preventiveservices. Evaluatelocallyobtainedsurveydataaboutscreeningratesandattitudesanddevisea

communityresponsetoincreasecolorectalcancerscreening.

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True Positive (TP)

False Positive (FP) 

(Type 1 error)

False Negative (FN) 

(Type II error) True Negative (TN)

SectionA:DiagnosticTestCharacteristicsScreeningprogramsusediagnosticteststoscreenfordisease.Thesetestsshouldfirstbeevaluatedbytheirabilitytodiagnosethetargetdisease.Thisevaluationisaccomplishedbystudyingtheperformanceofthetestinaclinicalpopulation.Youareaskedtoevaluatetheperformanceofafecaloccultbloodtest(FOBT)toscreenforcolorectalcancer(CRC).Thetestconsistsoftakingtwosamplesofstoolfromeachofthreeconsecutivestoolsandsmearingthesamplesontocards(onesampleperslide,twoslidespercard). Thestoolsamplesarethentestedforpresenceofoccultblood.Theresultsofthestooltestarereportedaseitherpositive(oneormoreslidespositive)ornegative(nopositiveslides).Ifthescreeningtestispositive,thepatientisreferredforadefinitivetesttodiagnoseCRC.Formulas:

Test Result 

 

      

Positive    

Negative 

 

Disease  Diseased  Non‐Diseased 

  

 Sensitivity = True Positive/ (True Positive + False Negative) Specificity = True Negative/ (True Negative + False Positive) PPV = True Positive/ (True Positive + False Positive) NPV = True Negative/ (True Negative + False Negative)

Question:

1. Whatisa“referencestandard”testforthediagnosisofcolorectalcancer?(i.e.,whatisadefinitivediagnostictestforthedisease?)

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YouhavethefollowingtableofdatafromthishypotheticalstudyofFOBT:

CRCpresent CRCabsent

FOBTpositive 40 26

FOBTnegative 80 854

(FOBT=FecalOccultBloodTesting,CRC=ColorectalCancer)

(The“referencestandard”wasusedtodeterminetheactualpresenceorabsenceofcolorectalcancerinthestudypopulation.)

Questions:

2 Calculatethefollowingcharacteristicsfromthedatainthetable:

a. Prevalenceofcolorectalcancer: b. SensitivityofFOBT: c. SpecificityofFOBT: d. PositivePredictiveValueofFOBT: e. NegativePredictiveValueofFOBT:

3. Howwouldthesenumberschangeiftheprevalenceofthediseasewerehalved?4. Whataretherelativestrengthsandweaknessesofthistestforuseinascreening

program?Whywouldweuseatestwithsuchalowsensitivityinascreeningprogram?

5. Thistesthasadichotomous(positive/negative)result.Howwouldyoucalculatethesecharacteristicsfortestswithcontinuousoutcomes(likebloodpressure,cholesterol)?

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SectionB:EvaluationofDiagnosticTestStudiesStudiesofdiagnostictestsshouldbeevaluatedaccordingtotheirvalidity,resultsandgeneralizability.YouarenowgivenmoredetailsaboutthehypotheticalstudyintroducedinSectionA.All1000studyparticipants(selectedfromgastroenterologists’officesin20sitesacrossthecountry)wereaskedtoperformthefecaloccultbloodtest(FOBT). Afterthat,thosewhohadapositivetest(definedasoneormoreslidespositiveforoccultblood)underwentacolonoscopy. Thosewhohadanegativetestweresentasurveyeachyearforthenextthreeyearstodeterminewhetherornottheyhadbeendiagnosedwithcolorectalcancer.Questions:1)Whataresomecriteriausedtoassessthevalidityofastudyofadiagnostictest?Wasthisstudyvalid?

2)Dotheresultsofthestudy(andthetestcharacteristicsderivedfromthem)show

thatthistest(FOBT)canaccuratelydiagnosecolorectalcancer?Howprecisearetheresults(arethereconfidenceintervalsgivenforsensitivity,specificity,etc.)?

3)Generalizability:Howwellwouldtheinformationfromthisstudyapplytothesamediagnostictestperformedinaprimarycarephysician’soffice(wheremostscreeningwouldlikelytakeplace)?

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SectionC:ScreeningProgramsAscreeningprogramconsistsofthescreeningtest,definitivediagnostictesting,andtreatmentforthedisease.Inmedicalpractice,physiciansmaychoosetoscreenapatientforadiseasebasedonavarietyoffactors,suchastheirtraining,numerous(andsometimesconflicting)guidelines,patientpreferences,andcommonlocalpractice.Thesefactorscaninfluencenotonlythedecisiontoscreenbutalsothemethodofscreening.Question:1. Whataresomecriteriathatwouldclassifyanyonescreeningprogramasdesirableandnecessaryforyourpracticeorashealthpolicy?Considerfactorsconcerning:thetestitself,thedisease,andthepatientstobescreened.

SectionD:EvaluationofScreeningProgramsThoughadiagnostictestcanaccuratelyscreenforadisease,itisstillimportanttoexaminewhethertheadoptionofthescreeningprogramleadstobetteroutcomesforthepatientsscreened.Questions:1. Whatisthebeststudydesigntoevaluatetheoveralleffectivenessofascreening

program?

2. Therearefiveimportantbiasesfoundinevaluationsofscreeningtestsandprograms:lead-timebias,length-timebias,over-diagnosisbias,selectionbiasandreferralbias.Explaineachofthese(withexamples)anddescribewaystoreduceeachone.

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SectionE:HealthPolicyExercise-ColorectalCancerScreeningTheknowledgethatyouhavegainedinthissessionhasmadeyoualocalexpertinscreeningandprevention.Youhavebeennotifiedbyanoutsidehealthpolicyagencyofanalarminglylowcolorectalcancerscreeningrateinyourcounty. YourgrouphasbeenaskedbytheHealthCommissionertoconfirmthisdataandtoexplorereasonswhythisratemightbelower. Youworkwithanepidemiologisttoconductatelephonesurveyofthepopulationaboutratesofcolorectalcancerscreening,theresultsofwhicharepresentedinHandout2. ThisstudywasarandomtelephonesurveyofresidentsofOnondagaCounty,NewYorkconductedinOctober2000.Analysisofthedemographicdatarevealedanunder‐representationofminoritiesinthesample.Examinethisdatafor“opportunitiestoimprove,”thenanswerthefollowingquestionsinyourgroups.Questions:1. Whatisthemostimportantreasonthatpeopledonotundergotherecommended

colorectalcancerscreeninginOnondagaCounty?2. Whatpatient-relatedfactorsmaycontributetothelackofrecommended

screening?

3. Whatcouldhealthprovidersdotoincreaseoverallscreeningratesinthecounty?

4. Whatcouldthehealthdepartmentdoforbothhealthprovidersandpatientsto increasescreeningrates?5. Whatdoyouthinkisthebestdiagnostictestforacommunityscreeningprogramforcolorectalcancer:scopes,suchascolonoscopyandsigmoidoscopy,radiologic interventionssuchasCTcolonographyanddoublecontrastbariumenema,or FOBT?

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Handout1:ScreeningProgramEvaluationCriteriaInthe1970'sand1980’s,PaulFrame,MDandothersevaluatedtheresearchevidencebehindthe“completephysical,”orashetermedit,the“AdultPeriodicHealthExamination,”andpublishedwhathefoundinasetofarticlesintheJournalofFamilyPractice.Fromthiswasdevelopedasetofcriteriathatcouldbeusedtoevaluateclinicalpreventiveservices. Thissetofcriteria,withmodifications,isusedbytheUSPreventiveServicesTaskForcetodevelopitsreportonClinicalPreventiveServices.Listedbelow,adaptedfromFrame'soriginalworkandtheoutlineoftheUSPSTFreports,aresomecriteriaforevaluatingascreeningtestforitsusefulnessinclinicalprevention.A.Considerationsregardingthediseaseforwhichtobescreened:

1.Thediseasemusthaveanasymptomaticstateandprogresstoasymptomaticstate.2.Thediseasemustbesufficientlyprevalentinthepopulation.3.Thediseasemustcausesignificantmorbidityandmortality.4.Theremustbetreatmentsavailablethatwillbeneficiallyimpactmorbidityandmortality.

B.Considerationsregardingthetestsforthedisease:

1.Thescreeningtestmustbeagoodtest(e.g.sensitivityandspecificity,positiveandnegativepredictivevalue).

2.Theevaluationofthescreeningprogrammustavoidthecommonsignificantbiases.3.Thescreeningtestmustbecost‐effective.

C.Considerationsregardingthepatient(s)tobescreened.

1.Thescreeningtestmustbeacceptabletothepatient.2.Thepatientmusthavesufficientlifeexpectancytoderivebenefitfromthepotentiallife

gainedbythescreeningprogram.

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Handout2A:LeadtimebiasPatientswhoarescreenedmayseemtolivelongerbecausetheywerediagnosedwiththediseaseearlierintheasymptomaticphase;however,thetimefromtrueonsetofdiseasetodeathisthesame.Inotherwords,thepatientisdyingatthesametime,butislabeledwiththediseaseforalongerperiodoftime.

Example:screeningforcancerandevaluatingbasedonlyon5‐yearsurvivalperiod–the5yearsmayincludetheleadtimeonlyandnotincreasedoverallsurvival.

Lead Time Bias

Pre-Symptomatic Disease Symptomatic Disease

Disease Onset Death (Age 55) (Age 67)

Lead Time

Screen-Detected Diagnosis Symptom-Stage Diagnosis (Age 60) (Age 65)

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Handout2B:Length-TimeBias Lengthtimesamplingbias(prognosticselection):Whentherearedifferingclinical

progressesofadisease(shortvs.longpre-clinicalperiods),screeningmayonlycatchlongpre-clinicalperioddiseaseinprogram. Example:Possiblyprostatecancer–Aretheredifferenttypeswithdifferentprognoses,or

arewemainlycatchingtheonethathastheleasteffectonhealth?

Screening Event

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Handout2C:Over-diagnosisBias Over-diagnosisbias:Whenthezealforscreeningprogramcausesover-interpretationof

testsaspositive(increasedfalsepositives)and,therefore,moretrulyhealthypeopleinthegrouparelabeledashavingthedisease. Example:Papsmears.Ifthetechniciansreadingthepapsmearsareovercalling

abnormalities,theresultisincreasedfalsepositivesandfalseincreasedsurvivaltimes.Therearenow“healthy”peoplethatarecategorizedashavingthedisease.Becauseofthis,therewillbeagreatersurvivalrateinthisgroup.

http://upload.wikimedia.org/wikipedia/commons/thumb/7/74/Overdianosissurvival.jpg/

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Handout2D: ReferralandSelectionBiasReferralbias:OccursifpersonsSEEKINGpreventivecaremaybehealthieroverallthanthoseshowinguponlyforacuteproblems. Thisisbestminimizedwitharandomizedcontroltrial(RCT)ofscreeninginacommunity(notatertiarycare)setting.

Example:Thosesubmittingtocolorectalcancerscreening–dotheyeatbetter,paymoreattentiontobloodinstool,etc.?

Selectionbias:Referralandlengthtimebiasesaretwoexamplesofselectionbiasinevaluationofscreeningprograms.Inaddition,makesurethesubjectsarefromacommunitysettingratherthanatertiarycaremedicalsetting.100IndividualswithColorectalCancerNosymptoms(n=22)

Symptomspresentbutignored(n=28) Consideredseekingmedicalcare;didnotduetobarriers(n=15)

Visiteddoctor(n=24) Visitedalternativecarepractitioner(n=7) Receivedhospitaloutpatientcare(n=3) Hospitalized(n=1)*

*Only 1% of hospitalized persons would receive their treatment in an academic medical center.

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Handout3:HealthPolicyExerciseDataHighlightedresultsoftheColorectalCancerScreeningSurvey,OnondagaCountyHealthDepartment,Syracuse,NY,October2000.StudyParticipants:

Totalcalls‐4318 Completed‐2331 Eligible‐800 Participated‐410Table1.Respondentsscreenedforcoloncancer. (FOBT<2yearsORflexiblesigmoidoscopy<5yearsagoORcolonoscopy<10yearsago)

Screened? %Yes 64No 32Noinformation 4

Table2.Reasonsgivenfornorecent(<2yearsago)FOBT

(N=164,morethanoneresponseperpersonaccepted)

Reason n=Don’tknow 21Fearofembarrassment 3Fearofbadnews 4NoaccesstoDr.’soffice 5Noconvenientappointments 0Doctorornursesaidscreeningnotneeded

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Noregulardoctor 5Noinsurance,can’tafford 3Toobusy 5Didn’tthinkofit 23Noonetoldme 40Noreason/noproblems 90

Table3.Impactofphysicianrecommendationforscreeningonscreeningrates.

Screened*YesNo

Total:

PhysicianAdvisedScreening? Yes 61 151 212 PhysicianAdvisedScreening? No 6 165 171

Total 67 316 383 *Recommendedscreening–FOBTannuallyplusflexiblesigmoidoscopyeveryfiveyearsORFOBTannuallyORflexiblesigmoidoscopyeveryfiveyears.

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Table4.Respondents’reportedsourcesofinformationaboutcolorectalcancerscreening.

ReprintedwithPermissions:BarrierstoColorectalCancerScreening:AComparisonofReportsfromPrimaryCarePhysiciansandAverage‐RiskAdults.CarrieN.Klabunde,PhD,*SallyW.Vernon,PhD,†MarionR.Nadel,PhD,etal.MedicalCare;Volume43,Number9,September2005

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Source %Atwork 1.5Radio 4.3Brochures,billboards,etc. 5.0Other 12.4Relative,friend,co‐worker 13.9Magazine,newspaper 25.4Television 28.8Physician/nurse 56.7

Handout4:Comparisonof2008ACS/USMSTF/ACRGuidelineswiththoseoftheUSPSTFInMarch2008,theAmericanCancerSociety,theU.S.Multi‐SocietyTaskForceonColorectalCancer,andtheAmericanCollegeofRadiologyreleasedaconsensusguidelineforcolorectalcancerscreening.InOctober2008theU.S.PreventiveServicesTaskForcealsoupdatedtheirscreeningrecommendations.

Asillustratedinthetablebelow,theseguidelinesaremoresimilarthandifferent.Theprimarymessagefromalloftheinvolvedorganizationsremains"Colorectalcancerscreeningsaveslives;ifyouare50orolder,chooseatestandgetscreened."Agetobeginandendscreening,andtestprioritization

Recommendation ACS/USMSTF/ACR USPSTF

Age to begin and end screening in average risk adults

Begin and age 50, and end screening at a point where curative therapy would not be offered due to life-limiting co-morbidity

Begin screening at age 50. Routine screening between ages 76-85 is not recommended. Screening after age 85 is not recommended.

Screening in high risk adults

Detailed recommendations based on personal risk and family history

No specific recommendations for age to begin testing or type of testing

Prioritization of tests

Tests are grouped into those that (1) primarily are effective at detecting cancer, and (2) those that are effective at detecting cancer and adenomatous polyps. Group 2 is preferred over group 1 due to the greater potential for prevention.

No specific prioritization of tests, though recommendations acknowledge that direct visualization techniques offer substantial benefit over fecal tests

Stool Testing, Guaiac based FOBT (gFOBT)

Annual screening with high sensitivity guaiac based tests

Annual screening with high sensitivity guaiac based tests

Stool Testing, Immunochemical-based FOBT (FIT)

Annual screening Annual screening

Stool Testing, Stool DNA (sDNA)

sDNA is an acceptable option Insufficient evidence to recommend for or against sDNA

Flexible Sigmoidoscopy

Screening every 5 years. Screening every 5 years, with annual gFOBT or FIT is an option

Screening every 5 years, with gFOBT every 3 years

Colonoscopy Screening every 10 years Screening every 10 years

CT Colonography

Screening every 5 years Insufficient evidence to recommend for or against CT colonography

Double Contrast Barium Enema (DCBE)

Screening every 5 years Not addressed

ReprintedbythepermissionoftheAmericanCancerSociety,Inc.fromwww.cancer.org.Allrightsreserved.1- Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint

Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of

Radiology Levin B, Lieberman D, McFarland B, et al. CA Cancer J Clin, May 2008; 58: 130 – 160.2- Screening for Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement U.S. Preventive Services Task Force; Annals of Internal Medicine 2008 149: 627-637

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