Crc talk for residents 2019

1. Colorectal Cancer
Screening and Diagnosis
Otto S. Lin, M.D., M.Sc.
Digestive Disease Institute
Virginia Mason Medical Center
Seattle, Washington, USA

2. When To Start Screening
Age & CRC Incidence/Mortality*
* African Americans at 45

3. MSTF Guidelines
Rex Gastro 2017
Modality Screening Interval
Low Sensitivity FOBT Not recommended
FIT* 1 yr
Sigmoidoscopy 5 yrs
DCBE 5 yrs
Colonoscopy 10 yrs
CTC 5 yrs
Fecal DNA 3 yrs
* Immunochemical tests or high sensitivity guaiac tests

4. Family History & CRC Risk
Butterworth Eur J Cancer 2006, Baglietto J Clin Epid 2006, Johns AJG 2006
Family History CRC Relative Risk
2º CRC 1.5
1º CRC 2.25
1º adenoma 1.99
1º CRC <45 3.87
Multiple 1º CRCs 4.25

5. High Risk Screening Guidelines
Rex Gastro 2017
* 40 years old or 10 yrs younger than age of diagnosis of youngest affected relative
† Advanced adenomas treated like cancers
Family
History
ACG ASGE AGA/ACS
Initial Intervals Initial Intervals Initial Intervals
Multiple 1°
CRC
40* 5 40* - 40* 5
1° CRC <60 40* 5 40* 3-5 40* 5
1° CRC ≥60 50 10 40 10 40
Average
Risk
1° adenoma
<60
50†
Average
Risk
40* 5 40* 5
1° adenoma
≥60
50
Average
Risk
40-50
Average
Risk
40
Average
Risk
2° or 3°
CRC or
adenoma
- - 50
Average
Risk
- -

6. CRC Screening Objectives
Remove adenoma and prevent CRC
Detect CRC at an earlier stage

7. Adenoma-Cancer Pathway

8. CRC Incidence Reduction
Winawer NEJM 1993
Removal of adenomas
during colonoscopy
reduces incidence of
CRC by 76-90%

9. CRC Mortality Reduction
Zauber NEJM 2012
Removal of adenomas
during colonoscopy
reduces CRC mortality
by 53%

10. CRC Screening Objectives
Remove adenoma and prevent CRC
Detect CRC at an earlier stage

11. Colon Cancer Stages

12. Staging & Survival
0%
50%
100%
0 3 6 9 12
Years after detection
Survival
Stage I
Stage II
Stage III
Stage IV

13. CRC Screening & Stage Shift
Amri Jama Surg 2013
• 217 screening CRC
vs 854 non-
screening CRC pts
• Screening leads to
stage shift

14. CRC Screening & Survival
Amri Jama Surg 2013
• 217 screening CRC
vs 854 non-
screening CRC pts
• Screening leads to
improved survival

15. FIT
• Detects microscopic blood in the stool
• Preferred over traditional guaiac testing
• Annual testing
• Not affected by diet
• DRE testing not recommended
• Disadvantages
 Relatively low sensitivity for polyps (40-50%)
 Positive result requires follow-up colonoscopy

16. FIT Accuracy For CRC
Lee AIM 2014

17. FOBT & CRC Mortality
0 0.5 1
Relative Risk for CRC Mortality
Selby
Mandel
Kronborg
Hardcastle

18. FOBT & Long-Term CRC Mortality
Shaukat NEJM 2013
Minnesota Colon
Cancer Control
Study
30 yr follow-up

19. Fecal DNA Test
• Colon cancer & precancerous polyps contain defined
mutations
• Can be detected in stool because cells constantly slough off

20. Cologuard Accuracy
Imperiale NEJM 2014
Basis for FDA approval and Medicare coverage

21. Cologuard Accuracy
Imperiale NEJM 2014

22. Fecal DNA Test Summary
• Advantages
 Safe, non-invasive, painless
 Relatively convenient (done at home)
 No bowel preparation
 No dietary or medication restrictions
 FDA approved & Medicare coverage
• Disadvantages
 Low sensitivity for small polyps
 Not indicated for high risk patients (FH)
 Patients with +ve tests need colonoscopy
 10% false +ve rate
• If –ve colonoscopy, do we need further workup?
 Expensive (if no insurance coverage)

23. Screening Colonoscopy
Colonoscopy
FOBT
Sigmoidoscopy
CT colonography
BE
Stool DNA
• Current gold standard for colon evaluation

24. Colonoscopy Accuracy
Van Rijn AJG 2006
• Even when competently
performed, colonoscopy
has significant miss rates
for large polyps

25. UK Flexible Sigmoidoscopy Trial
Atkin Lancet 2010
0
20
40
60
80
100
120
140
160
CRC Incidence* CRC Mortality* Overall Mortality**
Screen Control
HR=0.77
HR=0.69
HR=0.97
* cases/100,000 person-years
** cases/10,000 person-years

26. US PLCO Trial
Schoen NEJM 2012
FS reduces CRC incidence & mortality

27. Colonoscopy & CRC Mortality/Incidence
Baxter Singh Brenner Kahi
Overall L CRC R CRC Overall L CRC R CRC Overall L CRC R CRC SIR SMR
0.0
0.5
1.0
OR
Baxter AIM 2009, Singh Gastro 2010, Brenner JNCI 2010, Kahi CGH 2009

28. FS/Colonoscopy & CRC Mortality
Nishihara NEJM 2013
Nurses Health Study & Health Professionals Follow-up Study

29. Virtual Colonoscopy

30. 3-D Endoluminal View

31. 2-D Planar View
Colon Cancer

32. 5 mm Descending Colon Polyp

33. Renal Cell Carcinoma

34. CTC Major Studies
Sensitivity Specificity
Polyp Size ≥6 mm ≥10 mm ≥6 mm ≥10 mm
ACRIN (n=2531) 78% 90% 88% 86%
Italian IMPACT
(n=1103)
85% 91% 88% 85%
MGH (n=605) 59% 91% 94% 85%
Munich (n=307) 91% 92% 98% 93%
NNMC (n=1233) 89% 94% 96% 80%
Pickhardt NEJM 2003, Johnson NEJM 2008, Regge Jama 2009, Graser Gut 2009, Zalis AIM 2012

35. CTC Pros & Cons
Disadvantages
No polypectomy or biopsy
Many pts will need colonoscopy
Still requires bowel preparation
Radiation exposure
May not be cost-effective
Flat polyps
No insurance coverage
Advantages
Quick
Safe, non-invasive
No sedation required
More convenient
Extracolonic findings
Well-tolerated & high
acceptance

36. CRC Incidence & Mortality By Sex
Siegel CA Cancer J Clin 2017
Due to
treatment &
screening
improvements
Due to
screening
improvements

37. CRC Incidence In Young Persons
Siegel CA Cancer J Clin 2017

38. CRC Mortality In Young Persons
Siegel CA Cancer J Clin 2017

39. New ACS Guidelines
Wolf CA Cancer J Clin 2018

40. • Modeling show screening at 45 is cost-effective
 MISCAN-CRC, SimCRC, CRC-SPIN
 Efficiency ratio
 Screening colonoscopy, FS, CTC, FIT & fecal DNA all
CE
• 45 year olds are associated with low colonoscopy
risk & at their peak productive years
• Modeling suggests there is enough colonoscopy
capacity in the US for screening all 45-49 year
olds
Wolf CA Cancer J Clin 2018
Joseph Cancer 2016
Basis For New ACS Guidelines

41. • Modeling results may not be accurate
• COST-EFFECTIVENESS does not equal COST
 Estimated 22 million more screening pts
 $5.5 billion to prevent 900 CRC deaths for 45-49 yo
• Adverse events from colonoscopy
• Increase in patients who undergo subsequent
surveillance colonoscopies for small adenomas
• GI endoscopic resources may be diverted to
screening & surveillance
• “Healthy user effect” may increase health care
disparities between groups
Imperiale CGH 2018
Liang Gastro 2018
Corley Gastro 2018
Bretthauer AIM 2018
Potential Problems

42. Take Home Messages
• The main objectives of CRC screening is to detect CRC
earlier & to prevent CRC by removing adenomas
 Screening decreases the incidence of CRC
 Screening also leads to a “stage shift”, making CRC easier to
treat & improving survival
• CRC screening has reduced CRC incidence & mortality in
Americans over 50
• But CRC incidence & mortality in Americans under 50 have
increased in the last decade
• Current CRC screening prevalence still suboptimal (<80%)
• Starting CRC screening at 45 is controversial
 Cost-effective, but likely to be very costly
 Not endorsed by USPSTF & insurance