colorectal cancer screening and surveillance fda advisory committee march, 2002 david lieberman md...

Colorectal Cancer Screening Colorectal Cancer Screening and Surveillanceand Surveillance

FDA Advisory Committee FDA Advisory Committee March, 2002March, 2002

David Lieberman MDChief, Division of GastroenterologyOregon Health Sciences University

Preventing Cancer

Normal ColonNormal Colon Advanced Advanced AdenomaAdenoma

Raising the bar

MD

ColonColonCancerCancerDetectionDetection

Colon CancerColon Cancer PreventionPrevention

Colorectal Cancer ScreeningRecommendations

• FOBT annual• Sigmoidoscopy every 5 yrs• FOBT + Sigmoidoscopy• Barium Enema every 5-10 yrs• Colonoscopy every 10 yrs

U.S. PreventiveServices,1995

Am. CancerSociety,2001

AHCPR Multi-disciplinePanel, 1997

Am College Gastro“Preferred option”,

2000

Fecal Occult Blood Test

• RCT demonstrate mortality reduction (15-33%)

• Easy to perform

• Can be completed by primary providers

Fecal Occult Blood Test

• Poor sensitivity for one-time test

• Requires repeat testing

• Compliance with repeat testing poor

• Costs are deceptive

Detection of Advanced Neoplasiawith one-time test: 24%

Sigmoidoscopy

Evidence:Evidence:Case-Control Studies:60% reduction in CRC mortality in the examined portion of the colon

Sigmoidoscopy

Advantages:Advantages:- Detects early cancer or polyps- Can be performed by primary care providers

Limitations:Limitations:- Examines 1/3 of colon- Proximal lesions may not be detected

Detection of Advanced Neoplasia: VA Study Data

Sigmoidoscopy alone:Sigmoidoscopy alone:Detection: 70%

NEJM 2001; 345:555-60

FOBT alone:Detection: 24%

FOBT + Sigmoidoscopy:Detection: 76%

A

Barium Enema

• No Data in screening populations

• Miss rate for polyps > 1cm exceeds 50% (National Polyp Study)

Virtual CT

Virtual MR

Virtual Colon Imaging

• Attractive nameAttractive name• Sensitivity for large

polyps• Rapid exam

• Cost-effectiveness uncertain

• False positive rate increases cost

• Some patient discomfort

• Small polyp dilemmaSmall polyp dilemma

AdvantagesAdvantages LimitationsLimitations

Screening with Colonoscopy

AdvantagesAdvantages•Detection of early cancer and advanced adenomas•Indirect evidence for effectiveness

LimitationsLimitations• Risk• Costs• Resources

Screening with Colonoscopy

NEJM 2000;343;162-8 & 169-174

Lieberman Imperiale

n = 3121 n = 1994

Age 62.9 yrs 58.9 yrs

% male 96.8% 58.9%% of examscomplete 97.0% 97.0%% with AdvancedNeoplasia 10.6% 7.0%

Screening with Colonoscopy Evidence for Effectiveness

• National Polyp Study (1993):

• Selby et al (1992):

• Mandel et al (1993 and 2000):

- Polypectomy reduced cancer incidence

- Sigmoidoscopy reduced mortality…… in that portion of the colon examined

- FOBT screened patients had reduced mortality and incidence

Summary

• prevalence of advanced neoplasia increases

• prevalence of proximalproximal advanced neoplasia increases

• more patients with advanced neoplasia go undetected with FOBT and sigmoidoscopy

• colonoscopy may be more effective screening test in men after age 60 yrs.

With increasing age:With increasing age:

Colon Screening

FOBT

Sigmoidoscopy

Colon Imaging

Fecal markers

Colonoscopy

ColonoscopyColonoscopy

SurveillanceSurveillanceColonoscopyColonoscopy

Screening Issues

• Surveillance

• Risk

• Cost

• Resources

Colon Surveillance:Recommendations

FINDING INTERVAL

Adenoma >1cm 3 yrsMultiple adenomas 3 yrs1-2 tub. Adenoma < 1cm 3-5 yrs3-5 yrs

Surveillance accounts for 20-50% of cost of colon screening programs

Neoplasia in Asymptomatic Men

• Tubular adenoma <1cm 27.0

• Tubular adenoma >10mm 5.0

• Mixed/Villous 3.0

• High-grade dysplasia 1.6

• Invasive Cancer 1.0

Among patients with neoplasia, Among patients with neoplasia, 72% had only Tub. Adenomas < 1cm72% had only Tub. Adenomas < 1cm

%

N Engl J Med 2000; 343: 162

ADVANCEDADVANCED

10.6%10.6%

Surveillance

• Impact on cost of screening program

• Impact on available resources for screening

• Risk Management– Risk may be low for patients with small

adenomas– Could be reduced with chemoprevention

Risks of Screening Colonoscopy

• VA Cooperative Study:– n = 3196 exams

– mean age = 63.0 yrs

– Gender (% male) = 96.8

Gastrointest Endosc 2002; 55: 307-14

Risk of Screening Colonoscopy

Gastrointest Endosc 2002; 55: 307-14: VA Coop Study

Major Complications (Definite)Major Complications (Definite)GI bleed + hosp. or transfusion 7 (6) 0.22%Perforation 0New Atrial Fib 1 MI or CVA 4 (2) 0.12%Venous Thrombosis 1 (1)Other 4

ALL Definite 9/3196 0.3%

For Diagnostic only 2/1435 0.1%All complications 17 0.53%

Risk of Colonoscopy

• Significant Bleed – Prior studies 0.2-1.0%

– VA Coop 0.22 (all therapeutic)

• Perforation– Prior studies 0 - 0.2%

– VA Coop 0

Controlling Risk: - Training - Quality improvement

Colon Screening

Can we afford it ?Can we afford it ?

Cost of not screening

Cost of Cancer CareCost of Cancer CareEmotional CostsEmotional Costs

Missed opportunity for preventionMissed opportunity for prevention

Cost of Colon Cancer Screening

0

5

10

15

20

25

30

35

40

Cost ($)peraddedyear of life(x 1000)

Colon Hypertension Mammography CholesterolScreening

Resources: Supply and Demand

New Demand

Capacity

ScreeningColon

Colonoscopy: Indications

0

5

10

15

20

25

Polyp-Surv

+FOBT

BRBPR

Pain

Diarrhea

+FHx

ScreenScreen

Cancer Surv

Anemia FS/BaE IBD Constip.

CORI: National Endoscopic Database 2000-2001

Current Screening

Shifting Resources: Surveillance

N Engl J Med 2000; 343:162-8: VA Coop

72% of asymp. men with neoplasia had onlysmall tubular adenomas

Can we shiftresources fromsurveillance to

screening ?

Low Risk of Cancer

Supply and Demand

Demand Capacity

New Demand Increased capacity:- shift resources- improve efficiency

Summary of Screening GuidelinesPotentialPotential

StrategyStrategy EvidenceEvidence MortalityMortality LimitationsLimitations

FOBT RCT 20-50% - Need for repeat testing- Poor detection of advanced adenomas

Flexible Case- 50-55% - Miss-rate for Sigmoid (FS) Control proximal neoplasia

Barium/ none ?? 50-60% - False (+) ratesImaging - Poor sensitivity

Colonoscopy Indirect 70-80% - Invasive, higher risk

Intervention

Adenoma

Chemo-Prevention Surveillance

Advanced AdenomaCancer

Recurrence

Recurrence

Possible role ofchemo-prevention

Summary of Screening Guidelines

• Effectiveness of any screening program depends on patient compliance– In 1999, only 44% of adults aged 50 and older

had at least one recommended test at appropriate interval (MMWR, 2001)

• There are many obstacles to colon screening that reduce compliance

Challenges for the Future

• Identify risk factors for colorectal cancer– Stratify higher risk patients– Develop risk-reduction strategies

• Develop new tools to find high-risk patients– Genetic markers ( in blood or stool )– Circulating proteins– New imaging modalities

• Improve patient compliance