colorectal cancer screening and surveillance fda advisory committee march, 2002 david lieberman md...
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![Page 1: Colorectal Cancer Screening and Surveillance FDA Advisory Committee March, 2002 David Lieberman MD Chief, Division of Gastroenterology Oregon Health Sciences](https://reader035.vdocument.in/reader035/viewer/2022062309/56649c805503460f9493693d/html5/thumbnails/1.jpg)
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
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Preventing Cancer
Normal ColonNormal Colon Advanced Advanced AdenomaAdenoma
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Raising the bar
MD
ColonColonCancerCancerDetectionDetection
Colon CancerColon Cancer PreventionPrevention
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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
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Fecal Occult Blood Test
• RCT demonstrate mortality reduction (15-33%)
• Easy to perform
• Can be completed by primary providers
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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%
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Sigmoidoscopy
Evidence:Evidence:Case-Control Studies:60% reduction in CRC mortality in the examined portion of the colon
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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
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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
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Barium Enema
• No Data in screening populations
• Miss rate for polyps > 1cm exceeds 50% (National Polyp Study)
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Virtual CT
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Virtual MR
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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
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Screening with Colonoscopy
AdvantagesAdvantages•Detection of early cancer and advanced adenomas•Indirect evidence for effectiveness
LimitationsLimitations• Risk• Costs• Resources
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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%
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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
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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:
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Colon Screening
FOBT
Sigmoidoscopy
Colon Imaging
Fecal markers
Colonoscopy
ColonoscopyColonoscopy
SurveillanceSurveillanceColonoscopyColonoscopy
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Screening Issues
• Surveillance
• Risk
• Cost
• Resources
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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
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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%
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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
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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
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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%
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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
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Colon Screening
Can we afford it ?Can we afford it ?
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Cost of not screening
Cost of Cancer CareCost of Cancer CareEmotional CostsEmotional Costs
Missed opportunity for preventionMissed opportunity for prevention
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Cost of Colon Cancer Screening
0
5
10
15
20
25
30
35
40
Cost ($)peraddedyear of life(x 1000)
Colon Hypertension Mammography CholesterolScreening
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Resources: Supply and Demand
New Demand
Capacity
ScreeningColon
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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
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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
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Supply and Demand
Demand Capacity
New Demand Increased capacity:- shift resources- improve efficiency
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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
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Intervention
Adenoma
Chemo-Prevention Surveillance
Advanced AdenomaCancer
Recurrence
Recurrence
Possible role ofchemo-prevention
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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
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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