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