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

2. Preventing Cancer Normal Colon AdvancedAdenoma

3. Raising the bar MD ColonCancerDetection Colon Cancer Prevention Prevention

4. 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

5. Fecal Occult Blood Test RCT demonstrate mortality reduction (15-33%) Easy to perform Can be completed by primary providers

6. 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%

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

8. 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

9. Detection of Advanced Neoplasia: VA Study Data Sigmoidoscopy alone: Detection: 70% NEJM 2001; 345:555-60 FOBT alone: Detection: 24% FOBT + Sigmoidoscopy: Detection: 76% A

10. Barium Enema No Data in screening populations Miss rate for polyps > 1cm exceeds 50% (National Polyp Study)

11. Virtual CT

12. Virtual MR

13. 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

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

15. Screening with Colonoscopy NEJM 2000;343;162-8 & 169-174 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%

16. 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

17. 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:

18. Colon Screening FOBT Sigmoidoscopy Colon Imaging Fecal markers Colonoscopy Colonoscopy SurveillanceColonoscopy

19. Screening Issues Surveillance Risk Cost Resources

20. 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

21. 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%

22. 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

23. 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

24. Risk of Screening Colonoscopy Gastrointest Endosc 2002; 55: 307-14: 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 9/31960.3% For Diagnostic only 2/14350.1% All complications 170.53%

25. Risk of Colonoscopy Significant Bleed –Prior studies0.2-1.0% –VA Coop0.22 (all therapeutic) Perforation –Prior studies0 - 0.2% –VA Coop0 Controlling Risk: - Training - Quality improvement

26. Colon Screening Can we afford it ?

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

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

29. Resources: Supply and Demand New Demand Capacity Screening Colon

30. Colonoscopy: Indications Polyp-Surv +FOBT BRBPR Pain Diarrhea +FHx Screen Cancer Surv AnemiaFS/BaEIBD Constip. CORI: National Endoscopic Database 2000-2001 Current Screening

31. 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

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

33. 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

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

35. 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

36. 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