Colorectal Cancer Screening and Surveillance FDA Advisory Committee March, 2002 David Lieberman MD Chief, Division of Gastroenterology Oregon Health Sciences University

Preventing Cancer Normal Colon AdvancedAdenoma

Raising the bar MD ColonCancerDetection Colon Cancer Prevention Prevention

Colorectal Cancer Screening Recommendations FOBT annual Sigmoidoscopy every 5 yrs FOBT + Sigmoidoscopy Barium Enema every 5-10 yrs Colonoscopy every 10 yrs U.S. Preventive Services,1995 Am. Cancer Society,2001 AHCPR Multi-discipline Panel, 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 Neoplasia with one-time test: 24%

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

Sigmoidoscopy Advantages: - Detects early cancer or polyps - Can be performed by primary care providers Limitations: - Examines 1/3 of colon - Proximal lesions may not be detected

Detection of Advanced Neoplasia: VA Study Data Sigmoidoscopy alone: Detection: 70% NEJM 2001; 345: 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 Advantages Limitations

Screening with Colonoscopy Advantages Detection of early cancer and advanced adenomas Indirect evidence for effectiveness Limitations Risk Costs Resources

Screening with Colonoscopy NEJM 2000;343;162-8 & LiebermanImperiale n = 3121n = 1994 Age62.9 yrs58.9 yrs % male96.8%58.9% % of exams complete97.0%97.0% % with Advanced Neoplasia10.6%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 proximalprevalence of proximal 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:

Colon Screening FOBT Sigmoidoscopy Colon Imaging Fecal markers Colonoscopy Colonoscopy SurveillanceColonoscopy

Screening Issues Surveillance Risk Cost Resources

Colon Surveillance: Recommendations FINDINGINTERVAL Adenoma >1cm3 yrs Multiple adenomas3 yrs 3-5 yrs 1-2 tub. Adenoma < 1cm3-5 yrs Surveillance accounts for 20-50% of cost of colon screening programs

Neoplasia in Asymptomatic Men Tubular adenoma <1cm27.0 Tubular adenoma >10mm 5.0 Mixed/Villous 3.0 High-grade dysplasia 1.6 Invasive Cancer 1.0 Among patients with neoplasia, 72% had only Tub. Adenomas < 1cm % N Engl J Med 2000; 343: 162 ADVANCED 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:

Risk of Screening Colonoscopy Gastrointest Endosc 2002; 55: : VA Coop Study Major Complications (Definite) GI bleed + hosp. or transfusion7 (6)0.22% Perforation0 New Atrial Fib1 MI or CVA4 (2)0.12% Venous Thrombosis1 (1) Other4 ALL Definite 9/ % For Diagnostic only 2/ % All complications %

Risk of Colonoscopy Significant Bleed –Prior studies % –VA Coop0.22 (all therapeutic) Perforation –Prior studies % –VA Coop0 Controlling Risk: - Training - Quality improvement

Colon Screening Can we afford it ?

Cost of not screening Cost of Cancer Care Emotional Costs Missed opportunity for prevention

Cost of Colon Cancer Screening Cost ($) per added year of life (x 1000) Colon Hypertension Mammography Cholesterol Screening

Resources: Supply and Demand New Demand Capacity Screening Colon

Colonoscopy: Indications Polyp-Surv +FOBT BRBPR Pain Diarrhea +FHx Screen Cancer Surv AnemiaFS/BaEIBD Constip. CORI: National Endoscopic Database Current Screening

Shifting Resources: Surveillance N Engl J Med 2000; 343:162-8: VA Coop 72% of asymp. men with neoplasia had only small tubular adenomas Can we shift resources from surveillance to screening ? Low Risk of Cancer

Supply and Demand Demand Capacity New DemandIncreased capacity: - shift resources - improve efficiency

Summary of Screening Guidelines Potential StrategyEvidenceMortalityLimitations FOBTRCT20-50%- Need for repeat testing - Poor detection of advanced adenomas FlexibleCase-50-55%- Miss-rate for Sigmoid (FS)Control proximal neoplasia Barium/none?? 50-60%- False (+) rates Imaging- Poor sensitivity ColonoscopyIndirect70-80%- Invasive, higher risk

Intervention Adenoma Chemo- Prevention Surveillance Advanced Adenoma Cancer Recurrence Possible role of chemo-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