Clinical Presentation, Diagnosis, and Staging of Colorectal Cancer
Clinical Presentation, Diagnosis, and Staging of Colorectal Cancer
Clinical Presentation, Diagnosis, and Staging of Colorectal Cancer
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Feb2016.|Thistopiclastupdated:Mar29,2016.
INTRODUCTIONColorectalcancer(CRC)isacommonandlethaldisease.Itisestimatedthatapproximately134,490newcasesoflargebowelcancerare
diagnosedannuallyintheUnitedStates[1],includingapproximately95,270colonand39,220rectalcancers.Approximately49,190Americansareexpectedtodie
oflargebowelcancereachyear.AlthoughCRCmortalityhasbeenprogressivelydecliningsince1990atarateofapproximately3percentperyear[2],itstill
remainsthethirdmostcommoncauseofcancerdeathintheUnitedStates.Global,countryspecificincidenceandmortalityratesareavailablefromtheWorld
HealthOrganizationGlobocandatabase.
Incontrasttothesedeclines,theincidenceofCRCinmenandwomenundertheageof50hasbeensteadilyincreasingatarateof2.1percentperyearfrom1992
through2012[1].Theseincreasesaredrivenpredominatelybyleftsidedcancersingeneralandrectalcancerinparticular(3.9percentperyear)[3].Current
literaturesuggeststhatover86percentofthosediagnosedundertheageof50aresymptomaticatdiagnosis,andthisisassociatedwithmoreadvancedstageat
diagnosisandpooreroutcomes[4].Atpresent,screeningisnotrecommendedforindividualsundertheageof50unlesstheyhaveapositivefamilyhistoryora
predisposinginheritedsyndrome.(See"Screeningforcolorectalcancer:Strategiesinpatientsataveragerisk"and"Screeningforcolorectalcancerinpatientswitha
familyhistoryofcolorectalcancer"and"Colorectalcancer:Epidemiology,riskfactors,andprotectivefactors",sectionon'Incidence'.)
CRCisdiagnosedaftertheonsetofsymptomsorbecauseofoccultbleedinginthemajorityofpatients.ScreeningofasymptomaticindividualsforCRCis
advocatedbymajorsocietiesandpreventivecareorganizations.Screeninghasbeenshowntodetectasymptomaticearlystagemalignancyandimprovemortality.
However,whilecompliancewithCRCscreeningguidelinesissteadilyimproving,itisstillrelativelylow.(See"Screeningforcolorectalcancer:Strategiesinpatients
ataveragerisk".)
Theclinicalpresentation,diagnosis,andstagingofCRCwillbereviewedhere.Thepathology,prognosticdeterminants,andtreatmentofcolonandrectalcancerare
discussedelsewhere.
(See"Pathologyandprognosticdeterminantsofcolorectalcancer".)
(See"Overviewofthemanagementofprimarycoloncancer".)
(See"Surgicalresectionofprimarycoloncancer".)
(See"AdjuvanttherapyforresectedstageIII(nodepositive)coloncancer".)
(See"AdjuvantchemotherapyforresectedstageIIcoloncancer".)
(See"Adjuvanttherapyforresectedcoloncancerinelderlypatients".)
(See"Overviewofsurgeryforthetreatmentofprimaryrectaladenocarcinoma".)
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(See"Neoadjuvantchemoradiotherapyandradiotherapyforrectaladenocarcinoma".)
(See"Adjuvanttherapyforresectedrectaladenocarcinoma".)
CLINICALPRESENTATIONPatientswithcolorectalcancer(CRC)maypresentinthreeways:
Suspicioussymptomsand/orsigns
Asymptomaticindividualsdiscoveredbyroutinescreening(see"Screeningforcolorectalcancer:Strategiesinpatientsataveragerisk")
Emergencyadmissionwithintestinalobstruction,peritonitis,orrarely,anacutegastrointestinal(GI)bleed
Therearenosymptomsinthemajorityofpatientswithearlystagecoloncancerandthesepatientsarediagnosedasaresultofscreening.Althoughtheincreasing
uptakeofCRCscreeninghasledtomorecasesbeingdiagnosedatanasymptomaticstage,mostCRCs(70to90percentintwocontemporaryseries[5,6])are
diagnosedaftertheonsetofsymptoms.SymptomsofCRCaretypicallyduetogrowthofthetumorintothelumenoradjacentstructures,andasaresult,
symptomaticpresentationusuallyreflectsrelativelyadvancedCRC.(See"Screeningforcolorectalcancer:Strategiesinpatientsataveragerisk"and"Screeningfor
colorectalcancerinpatientswithafamilyhistoryofcolorectalcancer".)
SymptomsfromthelocaltumorTypicalsymptoms/signsassociatedwithCRCincludehematocheziaormelena,abdominalpain,otherwiseunexplainediron
deficiencyanemia,and/orachangeinbowelhabits[712].Lesscommonpresentingsymptomsincludeabdominaldistention,and/ornauseaandvomiting,which
maybeindicatorsofobstruction.Acompilationofthemostfrequentsymptomsandfindingsthatprompteddiagnosticcolonoscopyinaseriesof388consecutive
patientsdiagnosedwithaCRCbetween2011and2014includedthefollowing[5]:
Bloodperrectum(37percent).
Abdominalpain(34percent).
Anemia(23percent).
Sixpatients(1.9percent)hadincidentalcolonichypermetabolicactivitydetectedonapositronemissiontomography/computedtomography(PET/CT)image
doneforanotherreason.
Onlyfourindividuals(1.3percent)underwentdiagnosticcolonoscopybecauseofchangeinbowelhabits(diarrhea).
Ontheotherhand,amongthe28patientswhosediagnosiswasestablishedatthetimeofsurgery,themostcommonindicationsforemergentsurgerywere
obstruction(57percent),apreoperativediagnosisofacuteappendicitisonpreoperativeCTimagingwithacecaladenocarcinomafoundinthesurgicalspecimen(25
percent),andperforation(18percent).
Obstructivesymptomsaremorecommonwithcancersthatencirclethebowel,producingthesocalled"applecore"descriptionseenonradiologicimaging(image
1AB).
Amongsymptomaticpatients,clinicalmanifestationsalsodifferdependingontumorlocation:
AchangeinbowelhabitsisamorecommonpresentingsymptomforleftsidedthanrightsidedCRCsbecausefecalcontentsareliquidintheproximalcolon
andthelumencaliberislarger,andtheyarethereforelesslikelytobeassociatedwithobstructivesymptoms.
Hematocheziaismoreoftencausedbyrectosigmoidthanrightsidedcoloncancer.
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IrondeficiencyanemiafromunrecognizedbloodlossismorecommonwithrightsidedCRCs[13].Cecalandascendingcolontumorshaveafourfoldhigher
meandailybloodloss(approximately9mL/day)thantumorsatothercolonicsites[14].(See"Causesanddiagnosisofirondeficiencyanemiaintheadult",
sectionon'Searchforsourceofbloodandironloss'.)
Abdominalpaincanoccurwithtumorsarisingatallsitesitcanbecausedbyapartialobstruction,peritonealdissemination,orintestinalperforationleadingto
generalizedperitonitis.
Rectalcancercancausetenesmus,rectalpain,anddiminishedcaliberofstools.
Theseconceptscanbeillustratedbythedistributionoffindingsatpresentationinaseriesof253CRCsthatwerediagnosedandtreatedatateaching/national
referralhospitalinKenyabetween1993and2005,whichincluded140rectalcancers,54rightsidedcoloncancers,and59leftsidedcoloncancers(table1)[11].
MetastaticdiseasePatientsmayalsopresentwithsigns/symptomsofmetastaticdisease.Approximately20percentofpatientsintheUnitedStateshave
distantmetastaticdiseaseatthetimeofpresentation[1].CRCcanspreadbylymphaticandhematogenousdissemination,aswellasbycontiguousand
transperitonealroutes.Themostcommonmetastaticsitesaretheregionallymphnodes,liver,lungs,andperitoneum.Patientsmaypresentwithsignsorsymptoms
referabletoanyoftheseareas.Thepresenceofrightupperquadrantpain,abdominaldistention,earlysatiety,supraclavicularadenopathy,orperiumbilicalnodules
usuallysignalsadvanced,oftenmetastaticdisease.
Becausethevenousdrainageoftheintestinaltractisviatheportalsystem,thefirstsiteofhematogenousdisseminationisusuallytheliver,followedbythelungs,
bone,andmanyothersites,includingthebrain.However,tumorsarisinginthedistalrectummaymetastasizeinitiallytothelungsbecausetheinferiorrectalvein
drainsintotheinferiorvenacavaratherthanintotheportalvenoussystem.
UnusualpresentationsThereareavarietyofatypicalpresentationsofCRC.Theseinclude:
Localinvasionoracontainedperforationcausingmalignantfistulaformationintoadjacentorgans,suchasbladder(resultinginpneumaturia)orsmallbowel.
Thisismostcommonwithcecalorsigmoidcarcinomasinthelattercase,theconditioncanmimicdiverticulitis.
Feverofunknownorigin,intraabdominal,retroperitoneal,abdominalwallorintrahepaticabscessesduetoalocalizedperforatedcoloncancer[15,16].
StreptococcusbovisbacteremiaandClostridiumsepticumsepsisareassociatedwithunderlyingcolonicmalignanciesinapproximately10to25percentof
patients[17].Rarely,otherextraabdominalinfectionscausedbycolonicanaerobicorganisms(eg,Bacteroidesfragilis)maybeassociatedwithCRC[18].(See
"Clinicalmanifestations,diagnosis,andtreatmentofinfectionsduetogroupDstreptococci(Streptococcusbovis/Streptococcusequinuscomplex)",sectionon
'Associationwithcolonicneoplasia'.)
CRCultimatelyprovestobethesiteoforiginofapproximately6percentofadenocarcinomasofunknownprimarysites[19].(See"Adenocarcinomaof
unknownprimarysite".)
CRCmaybedetectedonthebasisofdiscoveryoflivermetastasesthataredetectedincidentallyduringstudiessuchasgallbladderorrenalultrasound,orCT
scansforevaluationofothersymptoms(eg,dyspnea).
ImpactofsymptomsonprognosisThepresenceofsymptomsandtheirparticulartypeprovidesomeprognosticimportance:
Patientswhoaresymptomaticatdiagnosistypicallyhavemoreadvanceddiseaseandaworseprognosis[5,20].Inonestudyof1071patientswithnewly
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diagnosedcoloncancer,217ofwhomwerediagnosedthroughscreening,thepatientsnotdiagnosedthroughscreeningwereatsignificantlyhigherriskfora
moreinvasivetumor(T3:relativerisk[RR]1.96),nodalinvolvement(RR1.92),andmetastaticdiseaseonpresentation(RR3.37).Inaddition,patientsnot
diagnosedthroughscreeninghadsignificantlyhigherdeathrates(RR3.02)andrecurrencerates(RR2.19)aswellasshortersurvivalanddiseasefree
intervals[20].(See"Testsforscreeningforcolorectalcancer:Stooltests,radiologicimagingandendoscopy".)
Thetotalnumberofsymptomsmaybeinverselyrelatedtosurvivalforcolonbutnotforrectalcancer[21].Whetherthedurationofsymptomsinfluences
prognosisisuncleartheavailabledataaremixed[2224].
Obstructionand/orperforation,althoughuncommon,carryapoorprognosis,independentofstage[8,2528].Amongpatientswithnodenegativecoloncancer,
obstructionorperforationarepoorprognosticfactorsthatmayinfluencethedecisiontopursueadjuvantchemotherapy.(See"Adjuvantchemotherapyfor
resectedstageIIcoloncancer",sectionon'Clinicopathologicvariables'.)
Tumorspresentingwithrectalbleeding(typicallythoseinvolvingthedistalcolonandrectum)havebeenthoughttohaveabetterprognosisbecauseoftheir
tendencytobediagnosedatanearlierstage[29,30]however,bleedingisnotanindependentpredictorofoutcome[26,31].Rectalbleedingismorecommonly
seenwithdistaltumors,andalargerproportionofdistalcoloncancerspresentasearlystagetumorsascomparedwithproximaltumors[30].
Otherdeterminantsofprognosis,includingclinicopathologicandmolecularfeatures,arediscussedelsewhere.(See"Pathologyandprognosticdeterminantsof
colorectalcancer".)
DIAGNOSISColorectalcancer(CRC)maybesuspectedfromoneormoreofthesymptomsandsignsdescribedaboveormaybeasymptomaticand
discoveredbyroutinescreeningofaverageandhighrisksubjects.OnceaCRCissuspected,thenexttestcanbeacolonoscopy,bariumenema,orcomputed
tomographycolonography.However,examinationoftissueisrequiredtoestablishthediagnosisthisisusuallyaccomplishedbycolonoscopy.(See"Screeningfor
colorectalcancer:Strategiesinpatientsataveragerisk"and"Screeningforcolorectalcancerinpatientswithafamilyhistoryofcolorectalcancer"and"Lynch
syndrome(hereditarynonpolyposiscolorectalcancer):Screeningandmanagement"and"Familialadenomatouspolyposis:Screeningandmanagementofpatients
andfamilies"and"Juvenilepolyposissyndrome".)
Histopathologically,themajorityofcancersarisinginthecolonandrectumareadenocarcinomas.ThehistologicdiagnosisofCRCisdiscussedindetailelsewhere.
(See"Pathologyandprognosticdeterminantsofcolorectalcancer",sectionon'Histologyandimmunohistochemistry'.)
ColonoscopyColonoscopyisthemostaccurateandversatilediagnostictestforCRC,sinceitcanlocalizeandbiopsylesionsthroughoutthelargebowel,
detectsynchronousneoplasms,andremovepolyps.SynchronousCRCs,definedastwoormoredistinctprimarytumorsdiagnosedwithinsixmonthsofaninitial
CRC,separatedbynormalbowel,andnotduetodirectextensionormetastasis,occurin3to5percentofpatients[3234].Theincidenceissomewhatlower
(approximately2.5percent)whenpatientswithLynchsyndromeareexcludedthepresenceofsynchronouscancersshouldraisetheclinicalsuspicionforLynch
Syndrome[35].(See"Lynchsyndrome(hereditarynonpolyposiscolorectalcancer):Clinicalmanifestationsanddiagnosis",sectionon'Colonicmanifestations'.)
Thepreparationfor,diagnosticuseof,andcomplicationsassociatedwithcolonoscopyarediscussedelsewhere.(See"Overviewofcolonoscopyinadults".)
Whenviewedthroughtheendoscope,thevastmajorityofcolonandrectalcancersareendoluminalmassesthatarisefromthemucosaandprotrudeintothelumen
(figure1).Themassesmaybeexophyticorpolypoid.Bleeding(oozingorfrankbleeding)maybeseenwithlesionsthatarefriable,necrotic,orulcerated(picture1A
B).Circumferentialornearcircumferentialinvolvementofthebowelwallcorrelateswiththesocalled"applecore"descriptionseenonradiologicimaging(image1A
B).
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Aminorityofneoplasticlesionsinthegastrointestinaltract(bothinasymptomaticandsymptomaticindividuals)arenonpolypoidandrelativelyflatordepressed.In
onestudy,nonpolypoidcolorectalneoplasmshadagreaterassociationwithcarcinomathandidpolypoidneoplasms[36].Cancersthatarisefromnonpolypoid(flat)
adenomasmaybemoredifficulttovisualizecolonoscopicallythanpolypoidlesions,butcolonoscopyisthoughttohavesuperiorsensitivityinthissituationthan
doesbariumenemaorcomputedtomography(CT)colonography.(See"Approachtothepatientwithcolonicpolyps",sectionon'Morphologic/endoscopic
classification'.)
Forendoscopicallyvisiblelesions,methodsfortissuesamplingincludebiopsies,brushings,andpolypectomy.Forlesionsthatarecompletelyremoved
endoscopically(withpolypectomy,endoscopicmucosalresection,orendoscopicsubmucosaldissection),tattooingisimportantforsubsequentlocalizationifan
invasiveneoplasmisfound,andadditionallocaltherapyisneeded.Tattoosaretypicallyplacedadjacenttoorafewcentimetersdistaltothelesion,withthe
locationbeingdocumentedinthecolonoscopyreport.Large,laterallyspreadingcolonicpolypscannowbesafelyremovedendoscopically,providedtheymeet
endoscopiccriteriathatpredicttheirbenignnature(table2).(See"Endoscopicremovaloflargecolonpolyps",sectionon'Patientselection'and"Approachtothe
patientwithcolonicpolyps",sectionon'Management'.)
Amongasymptomaticpatients,colonoscopicmissratesforCRCsinthehandsofexperiencedoperatorsrangefrom2to6percent,andarehighestontherightside
ofthecolon[3739].(See"Testsforscreeningforcolorectalcancer:Stooltests,radiologicimagingandendoscopy",sectionon'Sensitivityofcolonoscopy'.)
TheavailabledataconcerningmissratesforCRCamongsymptomaticpatientsundergoingcolonoscopyareasfollows:
InarandomizedtrialcomparingcolonoscopyversusCTcolonographyforindividualswithsymptomssuggestiveofCRCconductedbySIGGAR(Special
InterestGroupinGastrointestinalandAbdominalRadiology)investigators,noneofthe55cancersthatwerediagnosedinthecohortof1072patientswhowere
randomlyassignedtocolonoscopyweremissed[40].
Inasystematicreviewandmetaanalysisof25diagnosticstudiesprovidingdataon9223patientswithacumulativeCRCprevalenceof3.6percent(414
cancers),thesensitivityofopticalcolonoscopyfordetectionofCRCwas94.7percent(178of188,95%CI9097.2)[41].Thus,themissratewas5.3percent.
LargeretrospectivestudiesfromCanada[4244]andtheUnitedStates[45,46]haveusedadministrativedatabasestoidentifypatientsdiagnosedwithCRC
whohadhadacolonoscopyperformedforanyindication6to60monthspriortoCRCdiagnosis.Theseinterval,missed,orpostcolonoscopyCRCs
accountedfor6to9percentofallCRCsintheirseries.OtherstudiesofpostcolonoscopyCRC(sometimescalledintervalcancers)haveshownaclose
inverserelationshipbetweentheincidenceofthesecancersinacolonoscopist'spracticeandthatcolonoscopist'sadenomadetectionrate.(See"Overviewof
colonoscopyinadults",sectionon'Qualityindicators'.)
Ifamalignantobstructionprecludesafullcolonoscopypreoperatively,theentireresidualcolonshouldbeexaminedsoonafterresection.
Intheabsenceofanobstruction,wherecolonoscopyisincomplete,anotheroptionisPillCamcolon2,awirelesscolonvideoendoscopycapsuleapprovedfor
CRCscreening,althoughitsuseinpatientswithsymptomssuggestiveofCRC(eg,anemia,rectalbleeding,weightloss)iscontroversial.(See"Wirelessvideo
capsuleendoscopy",sectionon'Coloncapsuleendoscopy'and"Testsforscreeningforcolorectalcancer:Stooltests,radiologicimagingandendoscopy",section
on'Capsuleendoscopy'.)
FlexiblesigmoidoscopyOverthelast50years,agradualshifttowardrightsidedorproximalcoloncancershasbeenobservedbothintheUnitedStatesand
internationally,withthegreatestincreaseinincidenceisincecalprimaries(picture2).Becauseofthis,andbecauseofthehighfrequencyofsynchronousCRCs,
flexiblesigmoidoscopyisgenerallynotconsideredtobeanadequatediagnosticstudyforapatientsuspectedofhavingaCRC,unlessapalpablemassisfeltinthe
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rectum.Insuchcases,afullcolonoscopywillstillbeneededtoevaluatetheremainderofthecolonforsynchronouspolypsandcancers(see"Colorectalcancer:
Epidemiology,riskfactors,andprotectivefactors",sectionon'Incidence').Nevertheless,screeningforCRCusingaflexiblesigmoidoscopeisoneofthefew
modalitiesthathavebeenproventhroughrandomizedcontrolledtrialstoreduceCRCmortalityandincidence[40].
BariumenemaBariumenemaiswidelyavailableandmaybeusedtoinvestigatepatientswithsymptomssuggestingofCRC(image1AB)[47,48].However,
thediagnosticyieldofbothdoublecontrastbariumenema(DCBE)aloneandthecombinationofDCBEplusflexiblesigmoidoscopyislessthanthatofcolonoscopy
orCTcolonographyfortheevaluationoflowertractsymptoms[48,49].
TheyieldofDCBEalonewasaddressedinarandomizedtrialcomparingDCBEversusCTcolonographyin3838patientswithsymptomssuggestiveofCRC[48].
Ofthe2527patientsassignedtoDCBE,thedetectionrateforCRCorlargepolypswassignificantlylower(5.6versus7.3percentwithCTcolonography).Ratesof
additionalstudiesaftertheinitialprocedureweresignificantlylowerafterDCBEthanCTcolonography(18versus24percent)withthreeyearsoffollowup.The
needforadditionalstudiesfollowingCTcolonographywasduemostlytothehigherpolypdetectionrateCRCwassubsequentlydiagnosedinmorepatientswho
hadinitiallyundergoneDCBE(missrate14versus7percent).
Ifapolypormassisdetectedbybariumenema,colonoscopyisrecommendedtoestablishthehistology,removethepolyp,andsearchforsynchronouslesions.
CTcolonographyCTcolonography(alsocalledvirtualcolonoscopyorCTcolography)providesacomputersimulatedendoluminalperspectiveoftheairfilled
distendedcolon.ThetechniqueusesconventionalspiralorhelicalCTscanormagneticresonanceimagesacquiredasanuninterruptedvolumeofdata,and
employssophisticatedpostprocessingsoftwaretogenerateimagesthatallowtheoperatortoflythroughandnavigateacleansedcoloninanychosendirection.CT
colonographyrequiresamechanicalbowelprepthatissimilartothatneededforbariumenema,sincestoolcansimulatepolyps.(See"Overviewofcomputed
tomographiccolonography".)
CTcolonographyhasbeenevaluatedinpatientswithincompletecolonoscopyandasaninitialdiagnostictestinpatientswithsymptomssuggestiveofCRC.
IncompletecolonoscopyNoncompletionratesfordiagnosticcolonoscopyinsymptomaticpatientsareapproximately11to12percent[40,50].Reasonsfor
incompletenessincludetheinabilityofthecolonoscopetoreachthetumorortovisualizethemucosaproximaltothetumorfortechnicalreasons(eg,partiallyor
completelyobstructingcancer,tortuouscolon,poorpreparation)andpatientintoleranceoftheexamination.Inthissetting,CTcolonographyishighlysensitivefor
thedetectionofCRCandcanprovidearadiographicdiagnosis,althoughitcanovercallstoolasmassesinpoorlydistendedorpoorlypreparedcolonsitalsolacks
thecapabilityforbiopsyorremovalofpolyps[41,5154].
CTcolonographyshouldberestrictedtopatientswhoareabletopassflatusandcapableoftoleratingtheoralpreparation.Forclinicallyobstructedpatients,a
gastrointestinal(GI)protocolabdominalCTscanisagoodalternativetoCTcolonography.
InitialdiagnostictestSystematicreviewsofscreeningstudiesconductedinasymptomaticpatientssuggestthatCTcolonographyandcolonoscopyhave
similardiagnosticyieldfordetectingCRCandlargepolyps.Comparisonofthebenefitsandcostsofthetwoproceduresdependsonotherfactors,oneofthemost
importantofwhichistheneedforadditionalinvestigationafterCTcolonographyandtheexposuretoradiation,whichisparticularlyimportantwhererecurrent
scanningovertimemaybecontemplatedsuchasinscreening.(See"Radiationrelatedrisksofimagingstudies".)
Abnormalresultsshouldbefollowedupbycolonoscopyforexcisionandtissuediagnosis,orforsmallerlesions,additionalsurveillancewithCTcolonography.There
iscontroversyastothethresholdsizeofapolypthatwouldindicatetheneedfor(interventional)colonoscopyandpolypectomy.CTcolonographyalsohasthe
abilitytodetectextracoloniclesions,whichmightexplainsymptomsandprovideinformationastothetumorstage,butalsocouldgenerateanxietyandcostfor
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unnecessaryinvestigationandmayhavealowyieldofclinicallyimportantpathology[55].(See"Testsforscreeningforcolorectalcancer:Stooltests,radiologic
imagingandendoscopy",sectionon'Computedtomographiccolonography'.)
TheperformanceofdiagnosticCTcolonographyascomparedwithcolonoscopyinpatientswithsymptomssuggestiveofCRChasbeenaddressedinthefollowing
studies:
Asystematicreviewandmetaanalysisincluded49studies(11,551patients)inwhichpatientsunderwentCTcolonographyforthediagnosisofcolorectal
polypsandcancerwithsubsequentcolonoscopyforverificationofthefindings43studies(6668patients)examinedasymptomaticordiseaseenriched
population[41].Therewere394cancersinthesymptomaticpopulation(prevalence6percent)andatotalof414cancersintheentirecohort.CTcolonography
detected96.1percentofthehistologicallyprovencancers(95%CI93.997.7percent).Inasubsetof25studies(9223patients)inwhichthesensitivityof
colonoscopycouldbeassessedindependently(ie,whenthecolonoscopywasperformedwithoutknowledgeofthepriorCTcolonographyresult,ananalysis
whichincludedpredominantlydatafromasymptomaticindividuals),thesensitivityofcolonoscopywas94.7percent(178of188cancers,95%CI90.497.2
percent).
ThediagnosticperformanceofCTcolonographywasdirectlycomparedwithcolonoscopyintheSIGGARtrialinwhich1610patientswithsymptoms
suggestiveofCRCwererandomlyassignedtocolonoscopy(n=1072)orCTcolonography(n=538)[40].Theprimaryendpointwastherateofadditional
colonicinvestigationaftertheprimaryprocedurefordetectionofCRCorlarge(>10mm)polyps.DetectionratesforCRCandlargepolypswere11percentfor
bothprocedures.CTcolonographymissed1of29CRCsandcolonoscopymissednoneof55.However,patientsundergoingCTcolonographyweremorethan
threetimesmorelikelytogetadditionalcolonicinvestigations(30versus8percent).OnlyonethirdofthesepatientswerefoundtohaveCRCoralargepolyp.
Atleastonepreviouslyunknownextracolonicfindingwasreportedin60percentofthe475patientswhohadCTcolonographyandnodiagnosisofCRC.Most
werejudgedtobeclinicallyunimportant.Amongthe48patientswhowereinvestigatedfurtherforextracolonicfindings,onlyapproximatelyonethirdreceiveda
diagnosisthatexplainedatleastoneoftheirpresentingsymptomsandonlyninepatientswerefoundtohaveanextracolonicmalignancy.
Overall,CTcolonographyhadsuperiorpatientacceptabilitycomparedwithcolonoscopyintheshortterm(immediatelyafterthetest)butthebenefitsof
colonoscopy(beingmoresatisfiedwithhowresultswerereceivedandlesslikelytorequirefollowupcolonicinvestigations)becameapparentafterlongerterm
followup(threemonths)[56].
TheavailabledatasuggestthatCTcolonographyprovidesasimilarlysensitive,lessinvasivealternativetocolonoscopyinpatientspresentingwithsymptoms
suggestiveofCRC.However,giventhatcolonoscopypermitsremoval/biopsyofthelesionandanysynchronouscancersorpolypsthatareseenduringthesame
procedure,inourview,colonoscopyremainsthegoldstandardforinvestigationofsymptomssuggestiveofCRC.CTcolonographyispreferredoverbariumenema
whereaccesstocolonoscopyislimited.
PILLCAM2AcoloncapsuleforCRCscreeninghasbeenapprovedbytheEMAinEuropeandbytheUSFoodandDrugAdministration.IntheUnitedStates,it
isapprovedforuseinpatientswhohavehadanincompletecolonoscopy.WhileitsroleinscreeningforCRCisstilluncertain,itcouldbeconsideredinapatient
withanincompletecolonoscopywholacksobstruction.
LaboratorytestsAlthoughCRCisoftenassociatedwithirondeficiencyanemia,itsabsencedoesnotreliablyexcludethedisease.Thereisnodiagnosticrole
forotherroutinelaboratorytest,includingliverfunctiontests,whichlacksensitivityfordetectionoflivermetastases.
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TumormarkersAvarietyofserummarkershavebeenassociatedwithCRC,particularlycarcinoembryonicantigen(CEA).However,allthesemarkers,
includingCEA,havealowdiagnosticabilitytodetectprimaryCRCduetosignificantoverlapwithbenigndiseaseandlowsensitivityforearlystagedisease[57
60].AmetaanalysisconcludedthatthepooledsensitivityofCEAfordiagnosisofCRCwasonly46percent(95%CI0.450.47)[61].Nootherconventionaltumor
markerhadahigherdiagnosticsensitivity,includingcarbohydrateantigen199(CA199,pooledsensitivity0.30,95%CI0.280.32).
Furthermore,specificityofCEAisalsolimited.Inthepreviouslymentionedmetaanalysis,thespecificityofCEAfordiagnosisofCRCwas89percent(95%CI
0.880.92).NoncancerrelatedcausesofanelevatedCEAincludegastritis,pepticulcerdisease,diverticulitis,liverdisease,chronicobstructivepulmonarydisease,
diabetes,andanyacuteorchronicinflammatorystate.Inaddition,CEAlevelsaresignificantlyhigherincigarettesmokersthaninnonsmokers[62,63].
AnexpertpanelontumormarkersinbreastandcolorectalcancerconvenedbytheAmericanSocietyofClinicalOncology(ASCO)recommendedthatneitherserum
CEAnoranyothermarker,includingCA199,shouldbeusedasascreeningordiagnostictestforCRC[58].Asimilarrecommendationhasbeenmadebythe
EuropeanGrouponTumorMarkers[64].
However,CEAlevelsdohavevalueinthefollowupofpatientswithdiagnosedCRC.ASCOguidelinesrecommendthatserumCEAlevelsbeobtained
preoperativelyinmostpatientswithdemonstratedCRCtoaidinsurgicaltreatmentplanning,posttreatmentfollowup,andintheassessmentofprognosis[58]:
SerumlevelsofCEAhaveprognosticutilityinpatientswithnewlydiagnosedCRC.PatientswithpreoperativeserumCEA>5ng/mLhaveaworseprognosis,
stageforstage,thanthosewithlowerlevels.(See"Pathologyandprognosticdeterminantsofcolorectalcancer",sectionon'PreoperativeserumCEA'.)
ElevatedpreoperativeCEAlevelsthatdonotnormalizefollowingsurgicalresectionimplythepresenceofpersistentdiseaseandtheneedforfurther
evaluation.(See"Surveillanceaftercolorectalcancerresection",sectionon'Carcinoembryonicantigen'.)
FurthermoreserialassayofpostoperativeCEAlevelsshouldbeperformedforfiveyearsforpatientswithstageIIandIIIdiseaseiftheymaybeapotential
candidateforsurgeryorchemotherapyifmetastaticdiseaseisdiscovered.ArisingCEAlevelaftersurgicalresectionimpliesrecurrentdiseaseandshouldprompt
followupradiologicimaging.(See"Surveillanceaftercolorectalcancerresection".)
BloodbasedtestsforearlydetectionofCRC,ortomonitorforpostoperativerecurrence,areunderactivedevelopmentatpresent.Amongstthecontendersare
Sept9[65]andtheGeminitest[66,67].
DIFFERENTIALDIAGNOSISThesignsandsymptomsassociatedwithcolorectalcancer(CRC)arenonspecific,andthedifferentialdiagnosis,particularly
amongpatientspresentingwithofabdominalpainandrectalbleeding,isbroad.(See"Causesofabdominalpaininadults"and"Etiologyoflowergastrointestinal
bleedinginadults"and"Evaluationofoccultgastrointestinalbleeding"and"Approachtoacutelowergastrointestinalbleedinginadults".)
Manyconditionscausesignsorsymptomsthataresimilartocolorectaladenocarcinomasincludingothermalignanciesaswellasbenignlesionssuchas
hemorrhoids,diverticulitis,infection,orinflammatoryboweldisease.TheriskofCRCposedbyparticularsymptomshasbeenaddressedinthefollowingstudies:
Ametaanalysisof15studiesconcludedthatthesensitivityofindividualsymptoms(changeinbowelhabits,anemia,weightloss,diarrhea,abdominalmass)
forthediagnosisofCRCwaspoor(rangingfrom5to64percent),andspecificitywaslimited,aswouldbeexpectedforalowprevalencedisease[68].
However,thespecificitywas>95percentfordarkredrectalbleedingandforthepresenceofapalpableabdominalmassonexamination,indicatingthat
patientswithoutCRCrarelyhavethesefindingsandsuggestingthatthepresenceofeithermakesthediagnosisofaCRClikely.
TheassociationbetweenconstipationandCRCwasaddressedinametaanalysisof28crosssectionalsurveysandcohortstudies,whichdemonstratedno
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increaseintheprevalenceofCRCamongindividualswithconstipationastheprimaryindicationforcolonoscopy[69].
ApopulationbasedcasecontrolstudyofclinicalfeaturesbeforediagnosisofCRCconductedin21primarycarepracticesinExeter,DevonintheUnited
Kingdomincluded349patientsovertheageof40whowerediagnosedwithCRCoverafouryearperiodand1744controlswithoutCRCwhowerematched
byage,sex,andgeneralpractice[9].Primarycarerecordsfortwoyearsbeforediagnosiswerereviewedtoascertainsymptoms.Ofthe349casesstudied,
210(60percent)hadtumorsatordistaltothesplenicflexure,and126(36percent)wereproximaltoit,withtheremainderhavingmultipleorunknownsites.
TenfeatureswereassociatedwithCRCbeforediagnosisinunivariateanalysis,thelikelihoodratiosforCRCaccordingtosymptomswere:rectalbleeding10,
weightloss5.1,abdominalpain4.5,diarrhea3.9,constipation1.8,abnormalrectalexamination18,abdominaltenderness4.6,hemoglobin<10g/dL9.5,and
positivefecaloccultblood31.Thepositivepredictivevalues(PPVs)forabdominalpain,constipation,diarrhea,weightloss,andrectalbleedingwerehigherfor
olderpatients(70andover),especiallyrectalbleeding.Whensymptomswerecombined,thePPVwashighest(>10)forhemoglobin<10g/dLcombinedwith
abdominaltenderness.TheveryhighPPVforapositivefecaloccultbloodtestvalidatesthepolicyofpromptinvestigationofpatientswithpositivefecaloccult
bloodtests,particularlyifsymptomatic.(See"Testsforscreeningforcolorectalcancer:Stooltests,radiologicimagingandendoscopy",sectionon'Stool
basedtests'.)
Anothersystematicreviewof62studiesassessingtherelationshipbetweensymptomsandCRCusedestimatesofsensitivityandspecificitytocalculatea
diagnosticoddsratio(DOR=[sensitivity/(1sensitivity)]/[(1specificity)/specificity]),whichprovidedasinglesummarymeasureofaccuracyforeachsymptom
ahighDORindicatesahighcorrelationbetweenthesymptomandthedisease,whileaDORofonemeansthatthesymptompresenceisnobetterthan
chanceindiscriminatingbetweendiseaseandnondiseasedpatients[70].TheDORs,sensitivity,likelihoodratioofhavingthediseaseifthesymptomwas
present,andlikelihoodofhavingCRCintheabsenceofthesymptomforavarietyofsymptomsareoutlinedinthetable(table3).Theauthorsconcludedthat
onlyrectalbleedingandweightlosswereassociatedwiththepresenceofaCRCandeventhesehadrelativelylowDORs.
Thedifferentialdiagnosisofacolonicmassasseenonradiographicorendoscopicstudiesincludesanumberofbenignandmalignantdisorders,thedifferentiation
ofwhichcangenerallyrequiresbiopsyandhistologicevaluation(table4).Inparticular,raremalignanciesotherthanadenocarcinomasthatareprimarytothelarge
bowelincludeKaposisarcoma(KS),lymphomas,carcinoid(welldifferentiatedneuroendocrine)tumors,andmetastasesfromotherprimarycancers.(See
"Pathologyandprognosticdeterminantsofcolorectalcancer",sectionon'Histologyandimmunohistochemistry'.)
DisseminatedKScaninvolvethecolon,particularlyinpatientswithAIDS,manifestedascharacteristicviolaceousmaculesornodules[71].(See"AIDS
relatedKaposisarcoma:Clinicalmanifestationsanddiagnosis",sectionon'Gastrointestinaltract'.)
PrimarynonHodgkinlymphomaofthelargebowelmostcommonlyarisesinthececum,rightcolon,orrectumandusuallypresentsatanadvancedstagein
adults.Coloniclymphomatypicallyappearsasalargesolitarymass,althoughmultiplepolypoidlesionsordiffuseinvolvementcanoccur[72].(See"Clinical
presentationanddiagnosisofprimarygastrointestinallymphomas".)
Coloniccarcinoidtumorsarefoundmostcommonlyintheappendix,rectum,andcecum,andtheytendtodevelopatayoungeragethanadenocarcinomasof
thecolon.Appendicealandrectalcarcinoids,mostofwhicharelessthan2cm,appearassubmucosalnodulesandtendtobeindolent.Incontrast,primary
coloniccarcinoidtumorscanpresentaslargeapplecorelesions,whichcanbeclinicallyaggressiveandmaymetastasize.(See"Clinicalcharacteristicsof
carcinoidtumors".)
Metastasesfromotherprimarycancers,mostoftenovariancancer,canmimicaprimarylargebowelmalignancy.(See"Epithelialcarcinomaoftheovary,
fallopiantube,andperitoneum:Clinicalfeaturesanddiagnosis",sectionon'Differentialdiagnosis'.)
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STAGINGOncethediagnosisofcolorectalcancer(CRC)isestablished,thelocalanddistantextentofdiseaseisdeterminedtoprovideaframeworkfor
discussingtherapyandprognosis.Areviewofthebiopsyspecimenisimportantpriortomakingadecisionabouttheneedforclinicalstagingstudiesandsurgical
resection,especiallyforacancerouspolyp.Polypswithanareaofinvasivemalignancythathavebeencompletelyremovedandlackassociatedadversehistologic
features(positivemargin,poordifferentiation,lymphovascularinvasion)havealowriskoflymphaticanddistantmetastasesinsuchpatients,polypectomyalone
maybeadequate.Thisismoreeasilydeterminedifthepolypispedunculated.(See"Approachtothepatientwithcolonicpolyps".)
TNMstagingsystemTheTumorNodeMetastases(TNM)stagingsystemoftheAmericanJointCommitteeonCancer/UnionforInternationalCancerControl
(table5)isthepreferredstagingsystemforCRC[73].UseoftheolderAstlerCollermodificationoftheDuke'sclassificationisdiscouraged.
Themostrecent2010TNMstagingclassificationincludesanumberofchangescomparedwiththeolder2002classification[73]:
SubdivisionofT4lesionsintoT4a(tumorperforatesthesurfaceofthevisceralperitoneum)andT4b(directinvasionorhistologicadherencetootherorgans
and/orstructures).
FurthersubstagingofstageIIintoIIA(T3N0),IIB(T4aN0),andIIC(T4bN0)disease.
N1andN2categoriesaresubdividedaccordingtothenumberofinvolvednodes.
SatellitedepositsthatarediscontinuousfromtheleadingedgeofthecancerandlackevidenceofaresiduallymphnodeareclassifiedasN1cdisease.
SeveralstagegroupingsofstageIIIdiseasehavebeenrevisedbaseduponrefinementinprognosticstratification.
M1issubdividedintoM1aforsinglemetastaticsiteandM1bformultiplemetastaticsites.
ThesechangesweresupportedbyanalysisofdataonbothcolonandrectumcancerfromthepopulationbasedSurveillance,EpidemiologyandEndResults
(SEER)registry[74,75].However,therevisededitionoftheTNMstagingclassificationisnotusedinallcountries.Asexamples,insomeareasoftheNetherlands,
thefiftheditionoftheTNMstagingclassificationisstillusedpurposelyforrectalcanceraslatermodificationswerenotconsideredtorepresentanimprovement,
whereasinJapan,noneoftherevisedcriteriaonsatellitedepositsthatlackevidenceofaresiduallymphnodewereadoptedintheseventheditionoftheNational
CancerStagingManualeditedbytheJapaneseSocietyforCanceroftheColonandRectumbecauseofthelackofsufficientjustificationforthischange[76].
Radiographic,endoscopic,andintraoperativefindingscanbeusedtoassignaclinicalstage,whileassessmentofthepathologicstage(termedpT,pN,pM)requires
histologicexaminationoftheresectionspecimen.Preoperativeradiationandchemotherapycansignificantlyalterclinicalstaging[77]asaresult,posttherapy
pathologicstagingisdesignatedwithaypprefix(ie,ypT,ypN).(See"Pathologyandprognosticdeterminantsofcolorectalcancer".)
ClinicalstagingevaluationPreoperativeclinicalstagingisbestaccomplishedbyphysicalexamination(withparticularattentiontoascites,hepatomegaly,and
lymphadenopathy,andpotentialfixationofrectalcancers),computedtomography(CT)scanoftheabdomenandpelvis,andchestimaging.Althoughfrequently
obtainedpreoperatively,liverenzymesmaybenormalinthesettingofsmallhepaticmetastasesandarenotareliablemarkerforexclusionofliverinvolvement
(picture3).Thesinglemostcommonlivertestabnormalityassociatedwithlivermetastasesisanelevationintheserumalkalinephosphataselevel[78].
CTscanIntheUnitedStatesandelsewhere,thestandardpracticeatmostinstitutionsisthatallpatientswithstageII,III,orIVCRCundergochest,
abdomen,andpelvicCT,eitherpriortoorfollowingresection,anapproachendorsedbytheNationalComprehensiveCancerNetwork.Ingeneral,itispreferable
toobtainthesescanspriorto,ratherthanaftersurgery,asthescanresultswilloccasionallychangesurgicalplanning.
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AbdomenandpelvisInpatientswithnewlydiagnosedCRC,preoperativeabdominalandpelvicCTscanscandemonstrateregionaltumorextension,
regionallymphaticanddistantmetastases,andtumorrelatedcomplications(eg,obstruction,perforation,fistulaformation)[79,80].ThesensitivityofCTfor
detectingdistantmetastasisishigher(75to87percent)thanfordetectingnodalinvolvement(45to73percent)orthedepthoftransmuralinvasion(approximately
50percent)[79,8185].ThesensitivityofCTfordetectionofmalignantlymphnodesishigherforrectalthanforcoloncancersperirectaladenopathyispresumedto
bemalignantsincebenignadenopathyistypicallynotseeninthisareaintheabsenceofdemonstrableinflammatoryprocess(eg,proctitis,fistula,perirectal
abscess)[86].
CTscanisnotareliablediagnostictestforlowvolumetumoronperitonealsurfaces[87].ThesensitivityofCTfordetectingperitonealimplantsdependsonthe
locationandsizeoftheimplants.Inonestudy,thesensitivityofCTfornodules<0.5cmwas11percentanditwasonly37percentforimplants0.5to5cm[88].
Althoughcommonlyobtained,thenecessityofpreoperativeabdominal/pelvicCTforallpatientswithCRCisdebated.Inaretrospectivereviewof180resected
patients,only3of67patientshadincidentalfindingsonCTthatalteredthesurgicalapproach[84].Assessmentofhepaticmetastasesbyintraoperativeultrasound
andmanualpalpationofthelivermayprovideabetteryieldthanpreoperativeCT,particularlyforpatientswhoarefoundtohavetransmuralinvolvement(T3/4)atthe
timeofexploration[8991].However,theincreasinguseoflaparoscopiccolonicresectionsprecludesmanualpalpation,andevenwithopenproceduressurgeons
maynothaveadequateaccesstotheliverdependinguponthelocationoftheincisionandtheextentofadhesionsfrompriorsurgery.
Thefindingoflivermetastasesonpreoperativestudiesmaynotnecessarilyalterthesurgicalapproachtotheprimarytumor,particularlyinpatientswhoare
symptomaticfromtheirprimarytumor(eg,bleeding,impendingobstruction).Inpatientswithfourorfewerhepaticlesions,resectionmaybecurative,withfiveyear
relapsefreesurvivalratesof24to38percent.Althoughmostsurgeonsadvocateresectionoftheprimarytumorandsynchronoushepaticmetastasesattwo
differentoperations,someapproachbothsitesatthesametime.(See"Managementofpotentiallyresectablecolorectalcancerlivermetastases".)
ChestTheclinicalbenefitofroutineclinicalstagingwithchestCTisalsocontroversial.Atleastintheory,imagingofthechestmightbeofmorevaluefor
rectalcancersincevenousdrainageofthelowerrectumisthroughthehemorrhoidalveinstothevenacava,bypassingtheliver,andlungmetastasesmightbe
morecommon[92].
Themajorissueisthefrequentfindingofindeterminatelesions(10to30percent),whichaddtotheclinicalcomplexity(ie,shouldfurtherpreoperativediagnostic
workupbeundertaken)butareseldommalignant(7to20percent).Asystematicreviewof12studiesincluding5873patientsundergoingstagingforanewly
diagnosedCRC[93]foundthat732(9percent)hadindeterminatepulmonarynodulesonpreoperativechestCT.Ofthese,80(11percent)turnedouttobecolorectal
metastasesatfollowup.Generally,thepresenceofregionalnodalmetastasesatthetimeofresection,multiplenumbersofindeterminatepulmonarynodules,size
5mm,rectalascomparedwithcoloncancer,parenchymalversussubpleurallocationofthenodule,anddistantmetastaseselsewhereweresignificantly
associatedwithmalignancy,whilecalcificationwasassociatedwithabenignetiology.Overall,theriskofmalignancyformostpatientswithindeterminate
pulmonarynodules(approximately1percent)seemssufficientlylowthatfurtherpreoperativediagnosticworkupisunnecessary.
LiverMRIContrastenhancedmagneticresonanceimaging(MRI)ofthelivercanidentifymorehepaticlesionsthanarevisualizedbyCT,andisparticularly
valuableinpatientswithbackgroundfattyliverchanges[94].AmetaanalysisconcludedthatMRIisthepreferredfirstlineimagingstudyforevaluatingCRCliver
metastasesinpatientswhohavenotpreviouslyundergonetherapy[95].However,newergenerationCTscannersandtheuseoftriplephaseimagingduring
contrastadministrationhasimprovedsensitivityofCTfordetectionoflivermetastases.Incurrentpractice,liverMRIisgenerallyreservedforpatientswhohave
suspiciousbutnotdefinitivefindingsonCTscan,particularlyifbetterdefinitionofhepaticdiseaseburdenisneededinordertomakedecisionsaboutpotential
hepaticresection.(See"Managementofpotentiallyresectablecolorectalcancerlivermetastases",sectionon'Patientselection'.)
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PETscansPositronemissiontomography(PET)scansdonotappeartoaddsignificantinformationtoCTscansforroutinepreoperativestagingofCRC
[96,97].TheestablishedroleofPETscanninginpatientswithCRCasanadjuncttootherimagingmodalitiesisdescribedinthefollowingsettings:
Localizingsite(s)ofdiseaserecurrenceinpatientswhohavearisingserumcarcinoembryonicantigen(CEA)levelandnondiagnosticconventionalimaging
evaluationfollowingprimarytreatment.Inthissetting,PETscanningcanpotentiallylocalizeoccultdisease,permittingtheselectionofpatientswhomay
benefitfromexploratorylaparotomy[98101].(See"Surveillanceaftercolorectalcancerresection".)
Inanillustrativeseries,105suchpatientsunderwentPETscanningandsubsequentabdominopelvicCTscans[98].ComparedwithCTandotherconventional
diagnosticstudies,PETscanninghadahighersensitivity(87versus66percent)andspecificity(68versus59percent)forthedetectionofclinicallyrelevant
tumor.Inasecondreport,PETscanfindingsledtoapotentiallycurativeresectionin14of50patients(28percent)withelevatedserumCEAlevelsanda
completelynormalorequivocalconventionaldiagnosticworkup[99].
EvaluationofpatientswhoarethoughttobepresentorfuturecandidatesforresectionofisolatedCRClivermetastases.TheroutineuseofPETpriorto
attemptedresectionreducesthenumberofnontherapeuticlaparotomies.(See"Managementofpotentiallyresectablecolorectalcancerlivermetastases",
sectionon'PETscans'.)
RecentchemotherapymayalterthesensitivityofPETforthedetectionofcolorectallivermetastases,aneffectthoughtrelatedtodecreasedcellularmetabolic
activityofthetumor.However,generally,thebenefitofaPETscanistodetectextrahepaticmetastasesinpatientsconsideredliverresectioncandidates,andin
thissituation,itisappropriatetoobtainaPETpriortoinitiationofchemotherapy.Thissubjectisaddressedindetailelsewhere.(See"Managementofpotentially
resectablecolorectalcancerlivermetastases",sectionon'PETscans'.)
LocoregionalstagingforrectalcancerAnaccuratedeterminationoftumorlocationwithintherectumanddiseaseextentisnecessarypriortotreatmentin
ordertoselectthesurgicalapproachandtoidentifythosepatientswhoarecandidatesforinitialchemoradiotherapypriortosurgery.(See"Neoadjuvant
chemoradiotherapyandradiotherapyforrectaladenocarcinoma",sectionon'Indicationsforneoadjuvanttreatment'.)
Digitalrectalexamination(DRE),rigidsigmoidoscopy,transrectalultrasound,transrectalendoscopicultrasound,andpelvicMRIcanallassistindeterminingthe
needforradicalresectionversuslocalexcision,andwhetherthepatientisacandidateforpreoperativetherapy.Thissubjectisdiscussedelsewhere.(See
"Pretreatmentlocalstagingevaluationforrectalcancer".)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and"BeyondtheBasics."TheBasicspatient
educationpiecesarewritteninplainlanguage,atthe5thto6thgradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducation
piecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantin
depthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocatepatient
educationarticlesonavarietyofsubjectsbysearchingon"patientinfo"andthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Colonandrectalcancer(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Colonandrectalcancer(BeyondtheBasics)"and"Patientinformation:Colorectalcancertreatment
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
metastaticcancer(BeyondtheBasics)")
SUMMARY
Patientswithcolorectalcancer(CRC)maypresentinthreeways(see'Clinicalpresentation'above):
Patientswithsuspicioussymptomsand/orsigns
Asymptomaticindividualsdiscoveredbyroutinescreening(see"Screeningforcolorectalcancer:Strategiesinpatientsataveragerisk")
Emergencyadmissionwithintestinalobstruction,peritonitis,orrarely,anacutegastrointestinal(GI)bleed
AlthoughtheincreasinguptakeofCRCscreeninghasledtomorecasesbeingdiagnosedatanasymptomaticstage,mostCRCsarediagnosedafterthe
onsetofsymptoms(mostcommonlyrectalbleeding,abdominalpain,otherwiseunexplainedirondeficiencyanemiaand/orachangeinbowelhabits).Achange
inbowelhabitsisamorecommonpresentingsymptomforleftsidedascomparedwithrightsidedcancers.Hematocheziaismorelikelywithrectalthancolon
cancers,andoccultcolonicbleedingismorecommonwithcecalandascendingcoloncancers.(See'Symptomsfromthelocaltumor'above.)
OneinfivepatientswithCRCpresentswithmetastaticdisease.Themostcommonmetastaticsitesaretheregionallymphnodes,liver,lungs,and
peritoneum.(See'Metastaticdisease'above.)
UnusualpresentationsofCRCincludemalignantfistulaformation,feverofunknownorigin,sepsisfromStreptococcusbovisandClostridiumsepticum,and
adenocarcinomaofunknownprimary.(See'Unusualpresentations'above.)
ApositivefecaloccultbloodtesthasamuchhigherpredictivevalueforCRCthananysingleorcombinationofsymptoms,warrantinghighpriorityfor
colonoscopicfollowup.(See'Differentialdiagnosis'above.)
Thevastmajorityofcolonandrectalcancersareendoluminaladenocarcinomasthatarisefromthemucosa.Colonoscopyisthemostversatilediagnostictest
insymptomaticindividuals(see'Colonoscopy'above).Computedtomography(CT)colonographyprovidesasimilarlysensitive,lessinvasivealternativeto
colonoscopyinpatientspresentingwithsymptomssuggestiveofCRC.However,giventhatcolonoscopypermitsremoval/biopsyofthelesionandany
synchronouscancersorpolypsthatareseenduringthesameprocedure,colonoscopyremainsthegoldstandardforinvestigationofsymptomssuggestiveof
CRC.CTcolonographyispreferredoverbariumenemawhereaccesstocolonoscopyislimited.(See'Initialdiagnostictest'aboveand'Bariumenema'
above.)
Inpatientsinwhomfortechnicalreasonsthetumorcannotbereachedbycolonoscopy(eg,partiallyobstructingcancer,tortuouscolon,poorprep)orbecause
ofpatientintolerance,CTcolonographycanprovidearadiographicdiagnosis.
Oncethediagnosisisestablished,thelocalanddistantextentofdiseasespreadisdeterminedtoprovideaframeworkfordiscussingtherapyandprognosis.
Preoperativeclinicalstagingisbestaccomplishedbyphysicalexamination,CTscanoftheabdomenandpelvis,andchestimaging.(See'Clinicalstaging
evaluation'above.)
Positronemissiontomography(PET)scansdonotappeartoaddsignificantinformationtoCTscansforroutinepreoperativestagingofanewlydiagnosed
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CRCexceptfortheevaluationofpatientswhoarethoughttobecandidatesforresectionofisolatedCRClivermetastases.(See'PETscans'above.)
Additionalprocedures(digitalrectalexamination[DRE],rigidsigmoidoscopy,transrectalendoscopicultrasound,and/ormagneticresonanceimaging[MRI])are
indicatedforlocoregionalstagingofpatientswithrectalcancertoselectthesurgicalapproachandtoidentifythosepatientswhoarecandidatesforinitial
radiotherapyorchemoradiotherapyratherthansurgery.(See'Locoregionalstagingforrectalcancer'above.)
ThereisnodiagnosticroleforroutinelaboratorytestinginscreeningorstagingCRC.However,serumcarcinoembryonicantigen(CEA)levelsshouldbe
obtainedpreoperativelyandpostoperativelyinpatientswithdemonstratedCRCtoaidsurgicaltreatmentplanningandassessmentofprognosis.(See'Tumor
markers'above.)
ACKNOWLEDGMENTTheeditorialstaffatUpToDatewouldliketoacknowledgeDennisJAhnen,MD,whocontributedtoanearlierversionofthistopic
review.
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Topic2496Version51.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
GRAPHICS
Rectalcancerasseenonbariumenema
Doublecontrastbariumenemashowsaneccentricmassarisingfrom
theanteriorwalloftherectum(arrow).
CourtesyofJonathanKruskal,MD,PhD.
Graphic82202Version3.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Cancerofthecolonasseenonbariumenema
Doublecontrastbariumenemashowsanapplecorelesionsurrounding
thelumenofthedescendingcolon.
CourtesyofJonathanKruskal,MD.
Graphic75818Version3.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Symptomatologyofcolorectalcancersbaseduponanatomicsite
Symptomsatdiagnosis(percent)
Rectalbleeding 21 44 79
Tenesmus 12 16 31
Abdominalpain 77 84 60
Intestinalobstruction 15 27 44
Mucusdischarge 0 7 24
Changedbowelhabit 64 86 66
Datafrom:SaidiHS,KaruriD,NyaimEO.Correlationofclinicaldata,anatomicalsiteanddiseasestageincolorectalcancer.EastAfrMedJ200885:259.
Graphic88705Version1.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
ColoncancerseenonCTscanandcolonoscopy
(A)Computedtomographic(CT)scanshowingafillingdefectintheascending
colon(redarrow)alongwithaninvolvedlymphnode(yellowarrow).
(B)Coloncanceridentifiedintheascendingcolononsubsequentcolonoscopy.
Graphic83618Version1.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Adenocarcinomaofthecolon
Adenocarcinomaofthecolonmayhaveavarietyofappearancesonendoscopy.Panel
A:atypicalexophyticmassPanelB:afriablepolypoidmassPanelC:
circumferentialadenocarcinoma.
CourtesyofJamesBMcGee,MD.
Graphic74346Version1.0
Normalsigmoidcolon
Endoscopicappearanceofthenormalsigmoidcolonicmucosa.The
finevasculatureiseasilyvisible,andthesurfaceisshinyand
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
smooth.Thefoldsareofnormalthickness.
CourtesyofJamesBMcGee,MD.
Graphic55563Version1.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Necroticadenocarcinomaofthecolon
Endoscopyshowingnecroticcoloniclesionsthatusuallysuggestan
advancedstageofmalignancy.PanelA:severetissuedestructionhas
ledtonecrosisandbleedingPanelB:thelongstandingtumorhas
extendeddeeplyintothemucosaandbecomenecrotic.
CourtesyofJamesBMcGee,MD.
Graphic54234Version1.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Endoscopiccriteriasuggestingmalignancyofapolyp
Firmconsistency
Adherence
Ulceration
Friability
Graphic68868Version1.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Familialcoloncancer
Theseimagesarefroma38yearoldmanwhowasfoundtohave
hemepositivestool.Hisfatherandtwounclesdiedofcoloncancer
beforetheageoffifty.PanelA:Theinitialstudywasabariumenema
(althoughacolonoscopyismorecommonlyusedastheinitial
diagnosticstudyforhemepositivestools).Thebariumenemareveals
afillingdefectinthececum(arrow).PanelsBandC:ACTscanofthe
abdomenshowsalargeexophyticmass(coloredinpinkinpanelC)
involvingthececum(arrows).PanelD:Colonoscopyrevealsthatthe
largeexophyticlesionoccupiesmostofthececum.Adenocarcinoma
wasconfirmedbybiopsy.Despitethesizeofthelesion,thetumor
hadnotspreadbeyondthecolonicwall.
CourtesyofJamesBMcGee,MD.
Graphic51584Version2.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Symptomsassociatedwithcolorectalcancer
p<0.001
Blood:darkred 3.9 0.71 0.29 0.10 3.1 0.8
(1.79.2) (0.090.65) (0.030.28) (1.66.0) (0.61.1)
p=0.004
LR+:thelikelihoodratioofhavingcolorectalcancerinthepresenceofthesymptomLR:thelikelihoodratioofhavingcolorectalcancerintheabsence
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ofthesymptom.
*DOR:diagnosticoddsratio.NoassociationbetweensymptomandcancerifDOR=1.
AUC:AreaUnderthereceiveroperatingcharacteristicCurve.NoassociationbetweensymptomandcancerifAUC=0.5.
Bleedingofanytype.
Reproducedfrom:AdelsteinB,MacaskillP,ChanSF,etal.Mostbowelcancersymptomsdonotindicatecolorectalcancerandpolyps:asystematicreview.
BMCGastroenterology201111:65.Copyright2011Adelsteinetal.
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Causesofacolonicmass
Malignantlesions
Adenocarcinoma
Lymphoma
Carcinoidtumor
Kaposisarcoma
Prostatecancer
Benignlesions
Crohn'scolitis
Diverticulitis
Endometriosis
Solitaryrectalulcer
Lipoma
Tuberculosis
Amebiasis
Cytomegalovirus
Fungalinfection
Extrinsiclesion
Graphic66850Version3.0
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
TNMstagingforcolorectalcancer,7thedition
Primarytumor(T)
TX Primarytumorcannotbeassessed
T0 Noevidenceofprimarytumor
Tis Carcinomainsitu:intraepithelialorinvasionoflaminapropria*
T1 Tumorinvadessubmucosa
T2 Tumorinvadesmuscularispropria
T3 Tumorinvadesthroughthemuscularispropriaintopericolorectaltissues
T4a Tumorpenetratestothesurfaceofthevisceralperitoneum
T4b Tumordirectlyinvadesorisadherenttootherorgansorstructures
Regionallymphnode(N)
NX Regionallymphnodescannotbeassessed
N0 Noregionallymphnodemetastasis
N1 Metastasisin13regionallymphnodes
N1a Metastasisinoneregionallymphnode
N1b Metastasisin23regionallymphnodes
N1c Tumordeposit(s)inthesubserosa,mesentery,ornonperitonealizedpericolicorperirectaltissueswithoutregionalnodalmetastasis
N2 Metastasisinfourormoreregionallymphnodes
N2a Metastasisin46regionallymphnodes
N2b Metastasisinsevenormoreregionallymphnodes
Distantmetastasis(M)
M0 Nodistantmetastasis
M1 Distantmetastasis
M1a Metastasisconfinedtooneorganorsite(eg,liver,lung,ovary,nonregionalnode)
M1b Metastasesinmorethanoneorgan/siteortheperitoneum
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2/4/2016 Clinicalpresentation,diagnosis,andstagingofcolorectalcancer
Anatomicstage/prognosticgroups
Stage T N M Dukes MAC
0 Tis N0 M0
I T1 N0 M0 A A
T2 N0 M0 A B1
IIA T3 N0 M0 B B2
IIB T4a N0 M0 B B2
IIC T4b N0 M0 B B3
T1 N2a M0 C C1
T1T2 N2b M0 C C1
T3T4a N2b M0 C C2
T4b N1N2 M0 C C3
*Tisincludescancercellsconfinedwithintheglandularbasementmembrane(intraepithelial)ormucosallaminapropria(intramucosal)withnoextension
throughthemuscularismucosaeintothesubmucosa.
DirectinvasioninT4includesinvasionofotherorgansorothersegmentsofthecolorectumasaresultofdirectextensionthroughtheserosa,as
confirmedonmicroscopicexamination(forexample,invasionofthesigmoidcolonbyacarcinomaofthececum)or,forcancersinaretroperitonealor
subperitoneallocation,directinvasionofotherorgansorstructuresbyvirtueofextensionbeyondthemuscularispropria(ie,respectively,atumoronthe
posteriorwallofthedescendingcoloninvadingtheleftkidneyorlateralabdominalwalloramidordistalrectalcancerwithinvasionofprostate,seminal
vesicles,cervix,orvagina).
Tumorthatisadherenttootherorgansorstructures,grossly,isclassifiedcT4b.However,ifnotumorispresentintheadhesion,microscopically,the
classificationshouldbepT14adependingontheanatomicaldepthofwallinvasion.TheVandLclassificationsshouldbeusedtoidentifythepresenceor
absenceofvascularorlymphaticinvasionwhereasthePNsitespecificfactorshouldbeusedforperineuralinvasion.
Asatelliteperitumoralnoduleinthepericolorectaladiposetissueofaprimarycarcinomawithouthistologicevidenceofresiduallymphnodeinthe
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nodulemayrepresentdiscontinuousspread,venousinvasionwithextravascularspread(V1/2),oratotallyreplacedlymphnode(N1/2).Replacednodes
shouldbecountedseparatelyaspositivenodesintheNcategory,whereasdiscontinuousspreadorvenousinvasionshouldbeclassifiedandcountedin
theSiteSpecificFactorcategoryTumorDeposits(TD).
cTNMistheclinicalclassification,pTNMisthepathologicclassification.Theyprefixisusedforthosecancersthatareclassifiedafterneoadjuvant
pretreatment(eg,ypTNM).PatientswhohaveacompletepathologicresponseareypT0N0cM0thatmaybesimilartoStageGroup0orI.Therprefixisto
beusedforthosecancersthathaverecurredafteradiseasefreeinterval(rTNM).
DukesBisacompositeofbetter(T3N0M0)andworse(T4N0M0)prognosticgroups,asisDukesC(AnyTN1M0andAnyTN2M0).MACisthe
modifiedAstlerCollerclassification.
UsedwiththepermissionoftheAmericanJointCommitteeonCancer(AJCC),Chicago,Illinois.TheoriginalsourceforthismaterialistheAJCCCancer
StagingManual,SeventhEdition(2010)publishedbySpringerNewYork,Inc.
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Metastaticcoloncancer
Multiplelivermetastasesseenduringlaparotomyinapatientwith
coloncancer.
CourtesyofRichardBFreeman,Jr,MD.
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ContributorDisclosures
FinlayAMacrae,MDGrant/ResearchSupport:CSIRO[BowelCancer(butyrate)]Actelion[CDiff(cadazolidversusvancomycin)]Glutagen[CoeliacDisease]
CancerAustralia(resveratrol)Medtronics(capsuleendscopes).Consultant/AdvisoryBoards:CommonwealthScientificandIndustrialResearchOrganization
(CSIRO,Australia)InternationalSocietyforGastrointestinalHereditaryTumoursGastroenterologicalSocietyofAustraliaNIHColonFamilyRegisterAustralian
NationalBowelCancerScreeningProgramAustralianNationalBowelCancerScreeningProgram.JohannaBendell,MDNothingtodisclose.KennethKTanabe,
MDGrant/Research/ClinicalTrialSupport:NimbusTherapeutics[hepatocellularcarcinoma(ND654,AcetylCoACarboxylaseallostericinhibitor)].
Consultant/AdvisoryBoards:BestDoctors[GIcancersmelanoma(medicalcare)]PatentHolder,noroyaltieslicensingfeespaidtoauthor:EGFSNPtodetermine
riskforHCC(cirrhosis,hepatocellularcarcinoma)UseofEGFRinhibitorstopreventHCC(cirrhosis,hepatocellularcarcinoma).DianeMFSavarese,MDNothing
todisclose.ShilpaGrover,MD,MPHNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultilevelreviewprocess,
andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmustconformto
UpToDatestandardsofevidence.
Conflictofinterestpolicy
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