1. Screening for Colorectal Cancer (CRC) Nov, 2007 A Aljebreen, FRCPC Division of Gastroenterology KKUH, Riyadh

2. Colorectal cancer (CRC) CRC: Facts Who should be screened? Average vs high risk patients Which screening test (FOBT vs sigmoidoscopy vs Ba enema vs CT colonoscgraphy or colonoscopy) Recommendations

3. CRC: Adenoma-carcinoma sequence Normal Colon AdvancedAdenoma 10-20% Lifetime Risk Genetic Environmental Lifestyle 5-6% Lifetime Risk This progression probably takes at least 10 years in most people National Polyp Study: 76-90% reduction in Cancer incidence after polypectomy NEJM1993;328:901-6.

4. CRC and colorectal adenomas: How common? Colorectal cancer (CRC) is a worldwide problem, with an annual incidence of approximately 1 million cases and an annual mortality of more than 500,000. CRC is the second most common cause of cancer mortality among men and women.

5. CRC and colorectal adenomas: How common? According to the last National Cancer Registry report in Saudi Arabia (2001), CRC was ranked as the 3 rd. There is no clear data about prevalence of colorectal adenoma in Saudi population >50, however, small retrospective studies showed that prevalence of colorectal adenoma among symptomatic patients were 18-25%. Unsedated colonoscopy, Saudi Journal of Gastro 2003

6. KKUH experience: CRC Average age was 55 yr 50% presented with complete Large bowel obstruction. 35% already had mets. (72%) already stage C or D Saudi Journal of Gastro, 2007.

7. Screening of CRC It is complex, it requires: –considerable patient effort (fecal occult blood test slides, colonoscopy preparation, etc.), –sedation and –a health-care partner for some tests.

8. Successful screening programs: Requirements? awareness recommendation from the primary-care physician (national guidelines), patient acceptance, financial coverage, risk stratification, screening test, timely diagnosis, timely treatment, and appropriate follow-up.

9. CRC: Facts screening rates remain low!! <30% of eligible persons have had a screening test for CRC in western countries.

10. Risk Factors for CRC Sporadic/ Sporadic/ Average Risk 75% 75% Family History 15-20% HNPCC 5% FAP-1% IBD-1%

12. Who should be screened?

14. Who is High Risk? Familial Polyposis –Sigmoidoscopy in teenage years –Colectomy HNPCC –Colonoscopy in 20’s Family History: –Colonoscopy 10 years younger than index family case APC Mutation Mismatch Repair Genes

15. Clinical problem A healthy 50-year-old woman at average risk for colorectal cancer (i.e., age is her only risk factor) is scheduled to undergo a periodic examination. Which screening test for colorectal cancer should be recommended?

16. Which test? Ideal Screening: Target high-risk patients BEFORE BEFORE they develop cancer FOBT Sigmoidoscopy Colonoscopy

17. Fecal Occult-Blood Testing Sensitivity 24% The reduction in mortality risk (15 -33%) Recommendation (average risk patient) –Offer yearly screening with FOBT. –Patients with a positive test on any specimen should be followed up with colonoscopy. Hardcastle et al. Lancet 1996;348: 1472–1477. Kronborg et al. Lancet 1996;348:1467–1471.

18. What about genetic testing?

19. Stool Genetic Tests 33 pts with neoplasia and 28 without –Mutations: K-ras, p53, APC –Microsatellite instability marker (Bat-26) SensitivitySpecificity CA adenoma >1cm Ahlquist et al; Gastroenterol 2000; 119:1219-27

20. However, The optimal set of molecular markers remains to be determined, and The feasibility of such tests when applied to the general population is yet unknown.

21. Sigmoidoscopy- U.S. Studies Sensitivity* for 70% Advanced Neoplasia: 50-70% NEJM 2000; 343: 162-8; 169-74 More than 50% of proximal lesions Not Not detected 1.If all pts with adenoma on sigmoidoscopy, undergo colonoscopy that means 25% of pts will need colonoscopy 2.Less effective with increasing age 3.Recommendation: offer sig every 5 years, if any abnormality, do colonoscopy

22. ?Combination of FOBT +sig D Liberman et al, NEJM Aug 2001

23. Ba enema The sensitivity rate was – –32% in which the largest adenomas detected were <0.5 cm, – –53% for those e adenomas 0.6 to 1.0 cm, and – –48% for those > 1.0 cm.Recommendations: – –Offer Ba enema every 5 years WINAWER et al, NEJM 2000;342:1766-72.

24. Colonoscopy Best test for polyp detection (95% Sen and 95% Sp) Need once every 10 years (attractive!) Best test for cancer prevention Invasive (2/1000 risk of perforation) Costly Requires highly qualified endoscopist Recommendation: offer colonoscopy every 10 years

25. Problems The miss rate for polyps is 15–25% for adenomas smaller than 5 mm in diameter and 0–6% for adenomas of >10 mm. How to overcome this problem? –Obtain a clear informed consent –Document cecal intubation –Good prep –Take your time during withdrawals (6 minute rule) –Others (not yet!)

26. Average-Risk Screening: What is the “best” test? Mortality Cancer TEST Issues SensitivityReduction Prevention FOBT Needs annual test 30%30% + Sigmoid Misses proximal lesions 70% 50-60 % ++ Barium No evidence 48% ?? 50% ++ ColonoscopyExpensive 99% 75-80% ++++

27. Emerging Screening Tests

28. Virtual colonoscopy

29. Sensitivity – 35-96% for polyps>1cm False positive rates of 17% Miss flat lesions Inter-observer variability Need prep + air insufflation Radiation exposure Cost Issue of when to refer to colonoscopy? Ready???? Pickhardt et al NEJM 2003;349:2191-200. Fenlon et al, NEJM 1999;341:1496–1503. Yee et al, Radiology 2001;219:685–692.

30. Cost-effectiveness of CRC screening All standard options for CRC screening in average-risk individuals are cost-effective. They are as cost-effective as mammography and more cost-effective than other forms of medical screening (e.g., for cholesterol in hypertension).

31. WGO Recommendations: 2007 Cascade 1: Countries with high level of resources (financial, professional, facilities) and high colorectal cancer incidence and mortality. –People at average risk: Colonoscopy for average-risk men and women, starting at the age of 50 and every 10 years. Cascade 2-6: when limited colonoscopy and or flex sig resources.

32. RECOMMENDED TESTS IN PERSONS AT AVERAGE RISK FOR CRC

33. Colon Cancer Screening Recommendations for People With Familial or Inherited Risk

34. CONCLUSIONS Detection and removal of adenomas can prevent most colon cancers The variation in recommendations should not obscure the larger message that screening can reduce the rate of death from colorectal cancer. The variation should be interpreted in a positive way as giving clinicians several choices with respect to colorectal- cancer screening (availability, cost, safety, and quality)

35. CONCLUSIONS At present physicians should not be dogmatic about which test to use but, rather, should offer patients a choice among FOBT, sig & colonoscopy. They should discuss the features of each test with their patients, who may have their own perspectives and preferences (cost, safety, discomfort, and fear of cancer)

36. CONCLUSIONS Patients should be told about lifestyle measures that may reduce the risk of colorectal cancer, including – –avoiding obesity, – –exercising regularly, – –not smoking, – –and limiting their intake of alcohol and red meat.