1. Colorectal Cancer Screening & Surveillance: Anything New? Timothy C. Hoops, M.D.

2. Case A 53-year-old male presents to the office with a history of greater than 15 years of esophageal reflux symptoms including heartburn, regurgitation and episodes of hoarseness. He has been treated with omeprazole 20 mg once daily but has breakthrough symptoms at times for which he takes a 2 nd dose. He denies dysphagia. He has no family history of colon cancer His physical exam is unremarkable. What might you recommend?

3. Screening for Colon Cancer ACS estimates that in the US in 2014: – 136,830 new CRC diagnoses – 50,310 CRC deaths – Lifetime risk for CRC: Men5% Women4.7% 3rd leading cause of death in both men and women

4. Screening for Colon Cancer Ideal screening study – Prevalent disease – Effective – High sensitivity and specificity – Safe – Available – Convenient – Cheap

5. Incidence/Mortality - Heritage/Race Siegel, CA Cancer J Clin 2014;64:104

6. Screening Guidelines USPSTF – 2008 – Screening for CRC beginning age 50 to age 75 FOBT Sigmoidoscopy Colonoscopy Insufficient evidence for stool DNA & CT colonography – Recommend screening in 75-85 y/o based on individual considerations – Recommend against screening > age 85 Ann Intern Med. 2008; 149: 627

7. Screening Guidelines ACS, US Multisociety Task force and American College of Radiology – 2008 – Tests that detect adenomatous polyps and cancer (detect and prevent cancer) Flexible Sigmoidoscopy every 5 years, or Colonoscopy every 10 years, or Double Contrast Barium Enema every 5 years, or CT Colonography every 5 years Gastroenterology 2008; 134:1570

8. Screening Guidelines ACS, US Multisociety Task force and American College of Radiology – 2008 – Tests that primarily detect cancer Annual gFOBT with high test sensitivity for cancer, or Annual FIT with high test sensitivity for cancer, or sDNA, with high sensitivity for cancer, interval uncertain Gastroenterology 2008; 134:1570

9. Screening Guidelines American College of Gastroenterology Cancer Prevention tests offered first – Beginning age 50; age 45 in AA – Colonoscopy every 10 years – Alternatives: Sigmoidoscopy CT colonography – Family Hx CRC > age 60 – as per average risk < age 60 – start age 40 and Q 5 years Rex; Am J Gastroenterol 2009; 104:739

10. Screening Guidelines Cancer Detection tests for those declining prevention tests – Fecal immunochemical test – annual – Alternatives Hemoccult Sensa Fecal DNA Rex; Am J Gastroenterol 2009; 104:739

11. Screening In 1980’s and 1990’s, most screening was FOBT and sigmoidoscopy Since about 2000, most CRC screening in the US has been with colonoscopy No published randomized controlled trial of colonoscopy to date Has it been effective?

12. CRC Trends Siegel, CA Cancer J Clin 2014;64:104

13. Polypectomy – CRC Mortality Zauber AG et al. N Engl J Med 2012;366:687-696.

14. Colon Cancer and Screening Rates Yang, DX. Cancer 2014; 10:1002

15. Colon Cancer and Screening Rates Estimated number of cancers prevented over 3 decades: 236,000 to 550,000 Yang, DX. Cancer 2014; 10:1002

16. So what is wrong with colonoscopy as a screening study?

17. Screening for Colon Cancer Ideal screening study – Prevalent disease – Effective – High sensitivity and specificity – Safe – Available – Convenient – Cheap - $$$

18. Colorectal Cancer Screening Among Adults Aged 50 Years or Older, United States, 2010Z CHARACTERISTICFOBTaaENDOSCOPYbbEITHER FOBT or ENDOSCOPYcc Sex Men9.057.460.2 Women8.655.658.3 Age, years 50-648.052.355.2 65+9.761.263.7 Race/ethnicity White (non-Hispanic)9.258.561.5 Black (non-Hispanic)8.453.055.5 Asiandd6.944.545.9 American Indian/Alaska Nativeee 6.146.548.1 Hispanic/Latino5.645.347.0 Education, years ≤115.842.143.9 126.851.954.2 13 to 1511.059.563.1 16+10.466.769.2 Health insurance coverage Yes9.259.462.2 No1.617.818.8 Screening Rates

19. Effectiveness of Colonoscopy Reduction of cancers more in left colon than in right Biological differences Quality issues – Cecal intubation rates – Adenoma detection rates – Prep quality Split dose preps

20. CT Colonography

21. CT colonography Colonoscopy Global Sensitivity 66.8% (62.7–70.8%) 92.5% (89.0–95.2%) Specificity 80.3% (77.7–82.8%) 73.2% (67.7–78.1%) Subgroup analysis Lesions between 5 and 7 mm Sensitivity 77.1% (73.3–80.5%) 86.7% (81.3–91.0%) Specificity 87.4% (86.3–88.4%) 98.0 (97.1–98.6%) Lesions between 8 and 10 mm Sensitivity 86.7% (81.7–90.7%) 88.5% (81.5–93.6%) Specificity 90.0% (89.1–91.0%) 99.2% (98.6–99.5%) Lesions > 10 mm Sensitivity 91.2% (86.5–94.6%) 92.9% (86.0–97.1%) Specificity 87.3% (86.2–88.3%) 91.3% (89.9–92.5%) Martin-Lopez, Colorectal Disease 2013; 16:O82

22. CT Colonography Pooled sensitivity/specificity for advanced neoplasia and cancer CT colonography Colonoscopy Global Sensitivity 96.8% (89.0-99.6%)91.2% (80.7-97.1%) Specificity 99.0% (98.7-99.2%) 100% (99.9-100%) Martin-Lopez, Colorectal Disease 2013; 16:O82

23. CT Colonography Advantages: – Rapid – No sedation – Lower procedural risk – Extracolonic findings Disadvantages – Same prep as for colonoscopy (? prep-less procedures) – Discomfort with insufflation – Radiation – Contrast allergy – Need for a colonoscopy for positive findings

24. Fecal Immunochemical Testing FIT

25. FIT Antibody to human globin – Doesn’t cross react with dietary meats – No need to avoid foods with peroxidase activity – Measures colonic blood – upper GI globin is digested – Fewer samples needed than FOBT – Increased sensitivity and specificity compared to FOBT

26. Pooled sensitivity/specificity for FIT Lee, Annals of Internal Medicine. 160(3):171-181, February 4, 2014. 68.45%98.50%

27. FIT Relatively cheap Good sensitivity and specificity profile Higher participation rates than colonoscopy Not good for detecting polyps

28. Stool DNA Testing

29. Multiple studies with numerous DNA markers Target shed DNA from shed cells Look for DNA markers present in malignancies – Aberrantly methylated BMP3 and NDRG4 promoter regions – Mutant KRAS – actin – FIT

30. Imperiale TF et al. N Engl J Med 2014;370:1287-1297.

34. Serum Testing

35. Methylated Sept9 Sept9 encodes the protein Septin 9, part of a protein complex active in mitotic cell division Colon cancer has increased levels of mSEPT9 Initial studies showed increased serum levels of mSept9 in patients with colon cancer Initial retrospective case-control studies – Sensitivity 52% to 72% – Specificity 90 to 95%

36. mSept9 Prospective trial in screening population 7941 patients, 53 CRC cases, 3025 adenomas SensitivitySpecificity CRC (all) 48.2% (32.4-63.6%)91.5% (89.7-99.5%) – Stage I35.05% – Stage II63.05% – Stage III46.0% – Stage IV77.4% – Adv Aden11.2% Church, TR. Gut 2014; 63:317

37. Colon Cancer Screening So which test should be done?

38. The Best Test Is The One That Gets Done