New US CRC Guidelines:New US CRC Guidelines:Prevention vs. Early Prevention vs. Early
Detection Detection
C5 Summit: New YorkC5 Summit: New YorkJune 5, 2008June 5, 2008
David Lieberman MDChief, Division of GastroenterologyOregon Health Sciences University
Portland VAMC
Risk Factors for CRC
Sporadic/Sporadic/Average RiskAverage Risk 75%75%
IBD-1%Colitis
FamilyHistory15-20%
HNPCC 3%
FAP-1%
Colorectal Cancer
Normal ColonNormal Colon Advanced Advanced AdenomaAdenoma
10-20%Lifetime Risk
Genetic Environmental
Lifestyle
5-6% Lifetime RiskNational Polyp Study:National Polyp Study:76-90% reduction in 76-90% reduction in Cancer incidence Cancer incidence after polypectomyafter polypectomy
Guideline Process
• Prior guidelines from multiple organizations
• Consensus guideline included:– American Cancer Society– Multi-Society Task Force on Colorectal Cancer
• GI organizations and American College of Physicians
– American College of Radiology
• U.S. Preventive Services Task Force
Legislation (and making consensus guidelines) is like making sausage;
You do not want to know the details
Guideline Process
• Rules of evidence
• Where evidence was lacking:– Expert opinion– Areas for research noted
• Emphasis on Quality in each program
Lifestyle and Diet
Smoking
Alcohol
ObesityBMI
LittlePhysicalActivity
DietaryFat
Fiber
Micro-nutrientsFolate
CalciumVitamin DSelenium
Lieberman; JAMA 2003; Vogelaar, Cancer 2006; 107:1624
ScreeningScreening
NSAIDS/Aspirin
New CRC Guideline: Key Principles
• Distinguish between
– Early cancer detection tests
– Cancer prevention tests
• Establish minimum standard for early cancer detection tests
• Emphasis on quality
Raising the bar
MD
Colon CancerColon Cancer PreventionPrevention
Early ColonEarly ColonCancerCancerDetectionDetection
Average-Risk CRC Screening
Tests which primarilyTests which primarilydetect early cancerdetect early cancer
Tests which detect both Tests which detect both cancer and adenomascancer and adenomas
gFOBTFIT
-Advantage: Advantage: Home test, non-invasive Home test, non-invasive-Limitations Limitations Repeat test every 1-2 yrs Repeat test every 1-2 yrs Low cancer prevention Low cancer prevention Program effectiveness ?? Program effectiveness ??
Structural Exam
-Advantage: -Advantage: Potential for cancer preventionPotential for cancer prevention Infrequent: 5-10 yrsInfrequent: 5-10 yrs-Limitations: -Limitations: Bowel prepBowel prep Office/hospital visit Office/hospital visit
Levin B, Lieberman D, McFarland B et al: 2008 CRC Guideline
New Guideline:Tests which detect both early cancer and adenomas arepreferred
Fecal Occult Blood Test: FOBTFOBT
FOBT- One-time testing
Imperiale et al; NEJM 2004;351:2704-14Young et al; Am J Med 2002; 97: 2499-2507Morikawa et al; Gastroenterology 2005; 129: 422-8Levi et al; Ann Intern Med 2007; 146:244-55
Lieberman et al;NEJM 2001;345:555-60Imperiale et al; NEJM 2004;351:2704-14Collins, Lieberman et al; Ann Intern Med 2005; 142:81-5
% of patients with cancer% of patients with cancerwho have (+) testwho have (+) test
% of patients with serious% of patients with seriousPolyps who have (+) testPolyps who have (+) test
33-60%33-60%
11-50%11-50%
More than 50% ofMore than 50% ofpatients with seriouspatients with seriouspolyps will not bepolyps will not bedetected with one test !!!detected with one test !!!
New Guideline:Any recommended test must detect >50% of cancers with one test
Stool Genetic Tests - Issues
• One-time test can detect more than 50% of cancers
• Evolving
• Costly
Imperiale et al; NEJM 2004;351:2704-14Itzkowitz et al; Clin Gastro Hep 2007; 5: 111-7
FOBT: Mortality Reduction
Adherence at Adherence at Every level: 100%Every level: 100% 40%40%
PotentialPotentialMortality Mortality ReductionReduction
IF adherence to IF adherence to initial test: 75%initial test: 75%
IF adherenceIF adherenceto repeat testto repeat testafter (-) test: 67%after (-) test: 67%
IF rate of IF rate of colonoscopycolonoscopyafter (+) test: 75%after (+) test: 75%
< 20%< 20%
Effective – but only in a Effective – but only in a program of repeat testingprogram of repeat testing
Early Cancer Detection Tests
• Requires programmaticadherence with (+) and (-) tests
• Programmatic performance:
• Unlikely to result in much cancer prevention
gFOBTFIT
UNKNOWNUNKNOWN
Adenoma and Cancer Detection Tests
SigmoidoscopySigmoidoscopy::Evidence: Case-Control Studies
Efficacy: Mortality reduction left colon No benefit right colon
Program performance: under study PLCO, UK, Italy
CT Colonography
NEJM 2003; 349: 2191; JAMA 2004; 291:1713-9; Rockey: Lancet 2005;365: 305-11
ACRIN,2007 90 86ACRIN,2007 90 86
SensitivitySensitivity SpecificitySpecificityPickhardt 94% 96%Cotton 55 96Rockey 59 96
Lesions > 10mm
CT Colonography: Who should be referred for Colonoscopy ?
> 9mm> 9mm
5-10%5-10%>5mm>5mm
15-25%15-25%
ALL with polypsALL with polyps
50%50%
NEJM 2003; 349: 2191; JAMA 2004; 291:1713-9; Lancet 2005;365: 305-11Levin B, Lieberman D, McFarland B et al; 2008 CRC Screening Guideline
YES
YES
If largest polyp is 1-5mm: ??????
CT Colonography: Issues
• Inter-observer variability
• Detection of flat polyps• Bowel Prep• Radiation• Extracolonic findings• Intervals uncertain:
– After negative exam– After exam with small polyps
Low Resolution CTCLow Resolution CTC
Adenoma and Cancer Detection Tests
ColonoscopyColonoscopyEvidence: Cohort Studies
Efficacy: Uncertain, but extrapolated from FOBT and Sig studies
Quality in practice: unknown
Program performance: unknownNational colonoscopy study(Winawer)
Colonoscopy Screening Studies (n > 1000)
• Studies: 2000-20042000-2004– VA Cooperative Study ;NEJM: 2000; 343: 162-8 (n = 3121)– Indiana Study; NEJM 2000; 343: 169-74 (n = 1994)– CT Colonography studies (n = 2447) (Pickhardt, Rockey, Cotton)– Fecal DNA Study; NEJM 2004; 351: 2704-14 (n = 4404)– Spain, Am J Gastroenterol 2003; 98: 2648-54 (n = 2210)
• Studies: 2005-20062005-2006– Women: (Schoenfeld) NEJM 2005; 352: 2061-8 (n = 1463)– Taiwan; Gastrointest Endosc 2005; 61: 547-53 (n = 1708)– Japan, Gastroenterology 2005; 129: 422-8
(n = 21,805 with iFOBT)– Seattle, JAMA 2006; 295: 2357-65 (N = 1244)– Poland, NEJM 2006; 355: 1863-72 (n = 50,148) – Germany (n = 1.14M)
gFOBTFIT
Genetic/Genetic/ProteomicsProteomics
ImagingImaging
ColonoscopyColonoscopy
SurveillanceSurveillance
Colonoscopy
• Appropriate utilization
• High-quality exam to cecum
• Low rate of missed lesions
• Low rate of incompletely removed lesions
• Low rate of adverse events
QUALITYQUALITY
Depends on:Depends on:
Colonoscopy Issues
• Bowel Prep
• Quality Issues
– Missed lesions
– Safety
Obstacles to Screening:Perceptions
• Patient education:Screening works !!!
Obstacles to Screening:Perceptions
• It is not fun
• It is not effective
• It is not clear what test to use
• It costs too muchIt costs too much
FOBT
Flex-Sig
Colon
BaE
$$
Cost of not screening
Cost of Cancer CareCost of Cancer CareEmotional CostsEmotional Costs
Missed opportunity for preventionMissed opportunity for prevention
$50-100,000per case
Overcoming Obstacles
• Patient Education
• Provider Education
• Understanding obstaclesto compliance
Colon Screening in USA
0
10
20
30
40
50
60
70
80
1975 1980 1985 1990 1995 2000 2005 2007
Rate of - FOBT, - Flexible Sigmoidoscopy - Colonoscopy
%%
MammographyMammographyfor Breast Cancerfor Breast Cancer
CRC Age-adjusted incidence rates/100,000210,452 white Americans >21 yrs
0
5
10
15
20
25
30
35
78-80 81-83 84-86 87-89 90-92 93-95 96-98 2000 2010
Left Colon
Right Colon
SEER data; Rabeneck et al. Am J Gastroenterol 2003; 98: 1400
Lieberman et al; NEJM: 2000; 343: 162-8Imperiale et al; NEJM: 2000: 343: 169-74
AmericanAmericanCancer Cancer SocietySociety
Ronald Reagan 1985
Colonoscopy ScreeningColonoscopy ScreeningFOBT/Flex sig
Right Colon: No Change
Summary of 2008 CRC Screening Guideline
• Distinguishes:– Tests which detect early cancer
vs– Tests which detect both adenomas and cancer
• Adherence to programmatic testing is a problem– Therefore any one-time test should detect more than
50% of cancers
• Emphasis on Quality
Clear preferencefor tests which
may prevent cancerStool-Based Tests
Colonoscopy or CT Colonography
Raising the bar
MD
ColonColonCancerCancerDetectionDetection
1970’s1970’s
Colon CancerColon Cancer PreventionPrevention
1990’s1990’s
Colon ScreeningColon ScreeningQualityQuality
20082008
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