CRC screening saves lives Choosing a test Getting screened earlier for some

1. Colorectal Cancer Screening – 2016 UpdateHoward Zhang, MDChief of Gastroenterology and HepatologySumma Health System

2. Outline • 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

3. Why CRC Screening • 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%* *Pan, J et al, Am J Gastroenterol 2016; 111:355–365;

4. Why CRC Screening • 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 Zauber AG, Winawer SJ, et al. N Engl J Med 2012; 366:687-696

5. 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. 1o Screening Goal: CRC Prevention • CRC detection vs prevention cancer polyp

8. 1o Screening Goal: CRC Prevention • 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. Levin B, et al. CA cancer J Clin 2008; 58:130-160

9. Outline • 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

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. CRC Screening Test Option • 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 1. Rockey DC, et al. Lancet. 2005;365:305-311

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

14. ACG CRC Screening Recommendations 2009 • 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

15. FOBT *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. Colonoscopy vs FIT • 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 FIT - CRC detection, not prevention test Quintero E, et al. N Engl J Med 2012; 366:697-706

18. Flex Sigmoidoscopy • 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 Schoen R.E., Pinsky P.F., et al. N Engl J Med 2012; 366: 2345-2357 Nishihara R., Wu K., Lochhead P., et al. N Engl J Med 2013; 369: 1095-1105 Schoenfeld P, et al. N Engl J Med 2005; 352: 2061-8 Lieberman DA, et al. N Engl J Med. 2000; 343: 162-8

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

20. CT Colonography

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. Outline • 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

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

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

29. Outline • 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

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 1 week later Stage IIIA, T2N1M0

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. Hyperplastic Sessile serrated adenoma Serrated Adenoma

39. Outline • 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

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

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

42. Usefulness of FIT in Postpolypectomy Surveillance? • 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 Lane JM, Chow E. et al. Gastroenterology 2010;139:1918-1926

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. Outline • 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

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 Chan, et al. JAMA 2009; 302: 649-659 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 • Colonoscopy now • 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