- CRC screening is effective at lowering morbidity and mortality from colorectal cancer. New screening tests like stool DNA and colon capsule offer additional options but have not been shown to be more effective than current tests. - The 2016 USPSTF guidelines recommend starting CRC screening at age 50 and stopping at 75, but continuing screening from 75-85 should be individualized. A variety of screening tests are available and the best test is one that a patient will adhere to. - New data continues to support established screening tools like colonoscopy, FIT, and flexible sigmoidoscopy. New technologies show promise but require more research to define their optimal role in CRC screening.

1. Colorectal Cancer (CRC) Screening
for the Family Physician
What’s New?
Dr Jarrod Lee
Gastroenterologist & Advanced Endoscopist
1

2. 2
Scope
• Rational for CRC
Screening
• New Data, Current
Tests
• New Screening Tests
• New Guidelines
2

3. The Rationale for CRC Screening
• CRC is a major public health problem; screening
lowers morbidity and mortality
• Most (>80%) occur in average risk individuals;
screening should be applied to general population
• No reliable early symptoms; screening is only way for
early detection
• Natural history favours screening:
• Precancerous stage (adenoma) progress slowly to cancer
• Adenomas can be removed to prevent cancer
3

4. Natural History of CRC
41. Amersi et al. 2005. 2. Zauber et al. 2012

5. CRC Development Pathway
5

6. Sessile Serrated
Adenomas
• Cause up to 1/3 of CRC
• Do not bleed
• Hard to detect
6

7. Likelihood of Adenoma to Contain
CRC or HGD
7Pickhardt et al. 2010

8. National Polyp Study: CRC Incidence
8Winawer et al. 1993.

9. National Polyp Study: CRC Mortality
9Zauber et al. 2012

10. New Data, Current Tests
10

11. 11
Stool FIT

12. Annual FIT
• Mortality benefit for gFOBT proven by large
pragmatic RCTs
• Reduces CRC specific mortality by 9-22%
• FIT more sensitive than gFOBT
• Sensitivity: 73-88% for CRC, 22-40% for AA
• Specificity: 91-96% for CRC, 91-97% for AA
• Does not require bowel preparation
• Limited compliance: 53-67%
12

13. 13
CT Colonography (CTC)

14. CT Colonography (CTC)
• Diagnostic accuracy:
• Sensitivity: 67-94% for AA; 73-98% for polyps > 5mm
• Specificity: 86-98% for AA; 80-93% for polyps > 5mm
• Flat polyps will be missed
• Sensitivity lower without bowel preparation
• Risks:
• Perforation: 2 per 10,000 scans
• Ionizing radiation dose 1-7 mSv
• Extracolonic findings: 5-37% need further diagnostic work
up, < 3% need definitive treatment
14

15. Colonoscopy
15

16. Colonoscopy
• Sensitivity: 89-98% for AA; 75-93% for polyp > 5mm
• Mortality benefit for flexible sigmoidoscopy proven
by large pragmatic RCTs
• Risks:
• Perforation and major bleeding
• 12 per 10,000 screening colonoscopies
• Overdiagnosis and overtreatment of smaller lesions
• Highly operator dependent
16

17. Operator Factors 17

18. Poor Bowel Preparation
• Higher rate of missed lesions:
• Per adenoma miss rate 47.9% (18% high risk)
• Minimum standard for CRC screening program:
• 90% good preparation (Target: 95%)
18

19. Endoscopist factors proven in several important studies
•1% increase in ADR  3% decrease in CRC mortality
19

20. 20

21. What’s
New?
21

22. Stool DNA Test
22

23. Overview of Stool DNA
23

24. Biological Basis of Stool DNA
24

25. Cologuard
• FDA approval Aug 14 based on pivotal DeeP-C study
• Subsequent studies with similar design showed
similar results: Alaska and Netherlands studies
• Automated assay for tumour related DNA changes
25

26. Cologuard Biomarkers
26

27. 27

28. 28

29. • Pivotal Study: DeeP-C Trial
• 10,000 average risk asymptomatic patients
• Cologuard vs FIT; colonoscopy as reference
• Overall CRC sensitivity 92.3%, specificity 86.6%
29

30. CRC and AA Detection
30

31. Advanced Adenoma Sensitivity
31

32. Evolution of Stool Tests
32

33. 33
Septin 9 Test

34. The SEPT9 Gene
• Septins:
• Multifunctional ‘scaffolding’ proteins that provide
structural support during cytokinesis
• SEPT9 gene produces septin-9
• Appears to act as a tumour suppressor
• Active in cells throughout body
• In CRC cells: SEPT9 gene is hypermethylated and the
DNA is released into peripheral blood
• Methylated SEPT9 DNA can be detected by PCR
34

35. 35

36. Outcomes
• PRESEPT: 7941 patients vs colonoscopy
• CRC: sensitivity 68%; specificity 80%
• Advanced polyps: sensitivity 21%
• FIT comparison study: 301 patients vs FIT
• CRC sensitivity: 73% vs 68%
• CRC specificity: 81% vs 97%
• Admit study
• 420 patient noncompliant with screening guidelines
• 99.5% adherence
36

37. FDA Approval April 2016
• Controversial decision; voting as follows:
• Test is safe: 9 yes; 1 abstain
• Test is effective: 5 yes; 6 no
• Benefits outweigh risks: 5 yes; 4 no; 1 abstain
• Main concern was failure to outperform FIT
• Approved for CRC screening in average risk patients
who refuse FIT or colonoscopy
• Potential to increase overall participation rates
37

38. 38

39. China CRC Screening Guidelines
In 2015 National Guidelines, recommended as the
‘standard’ test with FOBT for CRC screening.
39

40. In Practice
• Easy to participate; no diet preparation or
medication alteration required
• Effective for CRC at all stages, and at all sites
• Colonoscopy required if positive
• Performed annually if negative
40

41. Colon
Capsule
41

42. 2nd Generation Colon Capsule
• 2 video cameras:
• 172 degrees each
• 4 images per second
• Battery: >10H
• Wireless Transmission
• Adaptive frame rate (AFR)
• Activated in small bowel
• Stationary: 4 fps; Moving: 35 fps
• Detects 85-90% more polyps (compared to PCC1)
42

43. PillCam Colon (PCC) 2 In Practice
• Bowel preparation crucial
• Need to use ‘boosters’
• Completion rate >90%
• Complications:
• Capsule retention 1%
• Related to bowel preparation
• Contraindications: same as small bowel capsule
43

44. 44

45. Official Recommendations
• FDA approval in 2012:
• Only after incomplete colonoscopy
• Patients should be able to undergo colonoscopy if a
clinically significant abnormality is found
• EU approval in 2006
• ESGE guidelines 2012:
• Feasible and safe and appears to be accurate when used in
average risk individuals (Evidence level 2++, grade C
recommendation)
• No formal role in CRC Screening as yet
45

46. 46
• 1292 patients with
PCC2 vs colonoscopy
• Polyps > 6mm
– Sensitivity 86%
– Specificity 88.1%
• Polyps > 10mm
– Sensitivity 87%
– Specificity 95.3%
• Cancers: 100%

47. CCE vs CTC
• Few studies to date
• Spada et al. Gut 2015.
• 100 patients with incomplete colonoscopy
• Polyps > 5mm: CCE 24.5% vs CTC 12.2%
• Polyps > 10mm: CCE 5.1% vs CTC 3.1%
• Relative sensitivity 1.67 – 2.0
• Rondonotti et al. Clin Gastro Hepatol 2014
• 66 patients with positive FIT
• Similar sensitivity 88% for polyps > 5mm
• 78% preferred CCE to CTC
47

48. The Future
• 3D visualization
• Panaromic visualization
• Automatic detection: current
accuracy for polyps: >90%
48

49. Cloud Based
Data
Management
49

50. 50
New Guidelines 2016

51. New Guidelines 2016
• USPSTF Guidelines published JAMA 2016
• “Screening tests are not presented in any preferred
or ranked order”
• “Goal is to maximize the total number of persons
who are screened because that will havethe largest
effect on reducing colorectal cancer deaths”
51

52. Life Years Gained
per 1000 Invidividuals Screened
52

53. CRC Deaths Averted
per 1000 Individuals Screened
53

54. Complications of CRC screening
Per 1000 Individuals Screened
54

55. Recommendations
• Start CRC screening at 50 years, stop at 75 years
• Screening for 75-85 years should be individualized
• Numerous screening tests available
• No head to head studies to demonstrate any test to be
more effective
• Clinicians should engage patients in informed
decision making about the screening strategy
• Patient’s preference
• High adherence over time
55

56. 56

57. Conclusion
• CRC Screening is
effective
• New data reinforces
current tools
• New tools offer
promise
• CRC screening will
continue to evolve
57

58. Thank You
58