1. Colorectal Cancer Screening – 2016 Update Howard Zhang, MD Chief of Gastroenterology and Hepatology Summa Health System

2. CRC screening saves lives Choosing a test Getting screened earlier for some Getting a colonoscopy Looking forward to next colonoscopy Gray area in real world practice Outline

3. Colorectal CA (CRC) impact in U.S. 2nd leading cause of death from cancer 3rd most common cancer diagnosed Most preventable cancers Adenomatous colon polyp removal prevents CRC (National Polyp Study) Colonoscopy reduces CRC incidence and mortality by 61%* Why CRC Screening * Pan, J et al, Am J Gastroenterol 2016; 111:355–365;

4. Colonoscopic removal of adenoma prevents death from colorectal cancer 2602 pts from NPS: had adenomatous polyps removed; followed 15.8 yrs 12 died of CRC 25.4 expected CRC death (SEER) 53% reduction in CRC mortality after adenomatous polypectomy Why CRC Screening Zauber AG, Winawer SJ, et al. N Engl J Med 2012; 366:687-696

6. Colonoscopy Screening: Evidence, Recommendations, and Public Support <1992: no controlled studies support any CRC screening 1992: sigmoidoscopy: case-control study (Selby, NEJM) 1993-6: FOBT: 3 RCTs (Minnesota, NEJM; UK, Den., Lancet) 1996: USPSTF recommends CRC screening, though colonoscopy is not an option 1997: GI Consortium recommends any of several tests, and colonoscopy is ‘an option’ (Gastroenterology 1997) 2000: ‘Colon cancer awareness month’ (March), celebrity endorsement, NEJM editorial (‘Going the distance..’)

7. CRC detection vs prevention 1o Screening Goal: CRC Prevention cancer polyp

8. American Cancer Society, US Multi- Society Task Force on CRC, and American College of Radiology Endorse CRC prevention as 1o screening goal but, clinician should offer screening choice effective  either at both early cancer detection and prevention through detection and removal of polyps  or primarily at early cancer detection. 1o Screening Goal: CRC Prevention Levin B, et al. CA cancer J Clin 2008; 58:130-160

9. CRC screening saves lives Choosing a test Getting screened earlier for some Getting a colonoscopy Looking forward to next colonoscopy Gray area in real world practice Outline

10. Levin B, et al. CA cancer J Clin 2008; 58:130-160

11. Rex DK, et al. Am J Gastroenterol 2009; 104:739-750

12. Double-contrast barium enema No longer considered a screening test by ACG and ASGE  Not useful in National Polyp Study  Detected only 48% of polyps > 1 cm1 ? Utility if incomplete colonoscopy CRC Screening Test Option 1. Rockey DC, et al. Lancet. 2005;365:305-311

13. Rex DK, et al. Am J Gastroenterol 2009; 104:739-750

14. Colonoscopy - preferred CRC prevention test If pt declines colonoscopy or other prevention test – annual FIT If pt declines colonoscopy, consider alternative prevention tests Flex sig CT colonography Other alternative detection tests include Fecal DNA Hemoccult Sensa ACG CRC Screening Recommendations 2009

15. FOBT  Guaiac  Immunochemical Detection method Reacts w/ pseudoperoxidase activity of heme portion of hemoglobin Reacts w/ Abs to globin portion of hemoglobin Sensitivity / Specificity Red meat, peroxidase- containing foods (eg, spinach) react, creating false postives; rehydration enhaces sensitivity but decreases specificity (S/S: 32%/98%)* Better sensitivity and specificity than guaiac (S/S: 67%/95%)* Restrictions Dietary restrictions; do not rehydrate; stop NSAIDs No need for dietary restrictions; stop NSAIDs *Allison J, et al. N Engl J Med. 1996;334:155-9

16. Colonoscopy vs FIT Quintero E, et al. N Engl J Med 2012; 366:697-706

17. Conclusions Pt more likely to participate in FIT screening than colonoscopy CRC detection similar in two groups More adenomas identified by colonoscopy FIT seems to detect mainly left-sided lesions Colonoscopy vs FIT Quintero E, et al. N Engl J Med 2012; 366:697-706 FIT - CRC detection, not prevention test

18. Associated w/ decrease in CRC incidence in both distal (21%) and proximal colon (14%); and 50% mortality (distal colon only)1 Associated w/ 40% decrease in CRC incidence in distal2, not proximal colon Women - more right-sided colon cancer?3 Sigmoidoscopy q5y + yrly FOBT increased detection rates of CRC from 70% to 76% (case-control trial)1 Flex Sigmoidoscopy 1. Schoen R.E., Pinsky P.F., et al. N Engl J Med 2012; 366: 2345-2357 2. Nishihara R., Wu K., Lochhead P., et al. N Engl J Med 2013; 369: 1095-1105 3. Schoenfeld P, et al. N Engl J Med 2005; 352: 2061-8 4. Lieberman DA, et al. N Engl J Med. 2000; 343: 162-8

19. CT Colonography 1. Bowel prep (similar to colonoscopy) 2. Air insufflation thru rectal tube 3. 2 CT scans: 1 prone and 1 supine 4. 3D “fly-through”

20. CT Colonography  Author  Journal NN  Size (mm)  Sensitivity %  Specificity %  Pickhardt  NEJM 2003  1233  At least 6  At least 10  89  94  80  96  Cotton  JAMA 2004  615  At least 6  At least 10  39  55  91  96  Rockey  Lancet 2005  614  6-9  10  51  59  96  Johnson  NEJM 2008  703  6-9  ≥10  78  90  86  95

21. CT Colonography CT colonography limitations Unable to remove detected polyp Polyps ≤ 6 mm & flat polyps not detected Bowel prep Inter-observer variability Radiation dosage 7 - 13 mSv, equivalent of 8 CXR Perforation risk 0.05-0.06% Cost associated with incidental findings Q5yr cumulative radiation dosage

22. Multitarget Stool DNA Test The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. $502/CologuardTM vs $8/FIT

23. Multitarget Stool DNA Test Cologuard detected 92% CRC and 42% advanced adenomas; FIT detected 74% CRC and 24% advanced adenomas. Imperiale, TF, et al. N Engl J Med 2014;370:1287-97.

24. CRC screening saves lives Choosing a test Getting screened earlier for some Getting a colonoscopy Looking forward to next colonoscopy Gray area in real world practice Outline

25. Rex DK, et al. Am J Gastroenterol 2009; 104:739-750

26. African American starts screening at age 45 Higher incidence and death rate for CRC Higher proportion of CRCs under age 50 compared with Caucasians (10.6% vs 5.5%) More right-sided lesions Unclear cause: genetic, dietary, lifestyle, socioeconomic, or preventive issues ? Insurance coverage for early screening ACG CRC Screening Recommendations 2009 Agrawal S, et al. Am J Gastroenterol 2005; 100 (3):515-523

27. ACG CRC Screening Recommendations 2009 Rex DK, et al. Am J Gastroenterol 2009; 104:739-750

28. ACG CRC Screening Recommendations 2009 Rex DK, et al. Am J Gastroenterol 2009; 104:739-750 Other high risk groups: FAP, AFAP, HNPCC, MAP (MUTYH-associated polyposis) etc Reference below Call GI or Oncology

29. CRC screening saves lives Choosing a test Getting screened earlier for some Getting a colonoscopy Looking forward to next colonoscopy Gray area in real world practice Outline

31. cold forceps polypectomy snare polypectomy

33. Rex DK, et al. Am J Gastroenterol 2009; 104:739-750

34. Small Polyp ≠ Benign Polyp TisN0M0

35. Small Polyp ≠ Benign Polyp Stage IIIA, T2N1M0 1 week later

36. Big Polyp ≠ Malignant Polyp Villous Adenoma

37. Common Colonic Polyp Type Adenomatous - CRC precursor Tubular; Villous; High grade dysplasia (HGD/Ca-in-situ) LRA: 1-2 adenomas < 10 mm HRA: 3 more adenomas, tubular ≥ 10 mm, villous adenoma, or HGD Hyperplastic - benign (mostly) Inflammatory - benign Serrated adenoma

38. Serrated Adenoma HyperplasticSessile serrated adenoma

39. CRC screening saves lives Choosing a test Getting screened earlier for some Getting a colonoscopy Looking forward to next colonoscopy Gray area in real world practice Outline

40. Surveillance After Screening and Polypectomy Lieberman DA, Rex DK, et al. Gastroenterology 2012;143:844-857

41. Surveillance After Screening and Polypectomy Lieberman DA, Rex DK, et al. Gastroenterology 2012;143:844-857 10 year: no polyp or distal small hyperplastic 5-10 year: LRA 3 year: HRA 1 year or sooner: > 10 adenomas, piecemeal resection Serrated lesions: table 1

42. Usefulness of FIT in Postpolypectomy Surveillance? Lane JM, Chow E. et al. Gastroenterology 2010;139:1918-1926 Interval positive FIT before scheduled surveillance colonoscopy identified advanced lesions earlier. CRC dx’ed 25 mo earlier Advanced adenoma dx’ed 24 mo earlier. Editorial critique – failure to evaluate baseline findings or examination quality hard to establish relationship of interval CRC

43. Usefulness of FIT in Postpolypectomy Surveillance? USMSTF: Interval FIT NOT recommended within the first 5 years after colonoscopy. Lieberman DA, Rex DK, et al. Gastroenterology 2012;143:844-857

44. Posttreatment Surveillance for Resected CRC Colonoscopy in 1 yr, then 3 yr, then 5 yr

45. CRC screening saves lives Choosing a test Getting screened earlier for some Getting a colonoscopy Looking forward to next colonoscopy Gray area in real world practice Outline

46. Dilemma in Clinical Practice How reliable is patient history? FHx of colon cancer? Personal history of colon polyps? Why did outside GI recommend sooner repeat colonoscopy? – esp when records are not available Polyp type & number? Prep quality? Incomplete exam or polypectomy? …

47. Dilemma in Clinical Practice Should environmental factors be factored in CRC screening? Risks for CRC development  Tobacco  Red meat and high fat diet  Alcohol  High BMI  Lack of physical activity  DM  Menopause Aspirin 81 mg qd reduces 20% new adenomatous polyps in pt w/ prior adenomas1,2 1. Chan, et al. JAMA 2009; 302: 649-659 2. Liao, et al. N Engl J Med 2012; 367:1596-1606

48. Dilemma in Clinical Practice When to stop screening or surveillance? 80 yo healthy WF with 2 small LRA removed 5 years ago a. Colonoscopy now b. No need to repeat colonoscopy

49. When to Stop Screening or Surveillance? USPSTF recommends individualized decision making from age 75-85 no further screening after age 85 ACS recommends 10 year life expectancy needed to benefit from screening

50. When to Stop Screening or Surveillance? American Geriatric Society recommends individualized decision making for older adults; pt input emphasized pt w/ short life expectancy should focus on conditions whose Tx has more immediate benefit burden associated w/ screening in the older person should be considered * American Geriatric Society Ethics Committee. Health screening decisions for older adults: AGS position paper. J Am Geriatr Soc. 2003 Feb; 51(2):270-1

51. CRC screening saves lives Adenoma removal led to 50-60% CRC mortality reduction 1o CRC screening goal – CA prevention Choosing a test Gold standard – colonoscopy FIT crucial in getting more screened Getting screened earlier for some Update on risk stratification Rex DK, et al. Am J Gastroenterol 2009; 104:739-750 Summary

52. Getting a colonoscopy Good result depending on good bowel prep and thorough test Looking forward to next colonoscopy Update on surveillance guideline Lieberman DA, Rex DK, et al. Gastroenterology 2012;143:844-857 Gray area in real world practice Clinical judgment tops guideline Summary