1. Update on Colon Cancer Screening and Prevention
Patrick R. Pfau, M.D.,
University of Wisconsin Medical School,
Director of Gastrointestinal Endoscopy
Section of Gastroenterology and Hepatology

2. Colorectal Cancer Lifetime incidence 5%
90% of cases occur after age 50
One-third of patients with colorectal cancer die from the disease
Only approximately 50 % of patients are screened for colorectal cancer
Colorectal cancer is a preventable disease

7. Colon polyps Two-thirds of polyps are adenomas (dysplasia)
Adenoma prevalence 25% at age 50 and 50% by age 70
Risk of cancer increases with polyp size, number, and histology
The polyp examined is representative of the individual’s propensity to form polyps and cancer

8. Adherence Rates – Cancer Screening
U.S. Adherence Rates
Breast Cancer 69% *
Cervical Cancer 86% *
Prostate Cancer 75%**
Colorectal Cancer 45% * 63%**
* Seeff Cancer 2002;95:
**Sirovich JAMA 2003;289:
Although awareness of colorectal cancer is increasing, adherence rates for colorectal cancer screening are below those of breast, cervical and prostate cancer, even though the evidence base to support colorectal cancer screening is stronger than for any of the other cancers, and colorectal cancer screening is more cost-effective than these cancers.

9. Colon Cancer Screening – When to Begin ?
Average risk – begin at age 50
Family risk factors
Primary degree relative doubles risk
Begin screening at age 40 or 10 years earlier than diagnosis of relative
Colon cancer syndromes (5-10% of colon CA)
Hereditary non-polyposis colorectal cancer (HNPCC)*
Colonoscopy every 1-2 years beginning at age 20-25
Familial Adenomatous Polyposis (FAP)

10. CRC Screening Guidelines- Average Risk
GI Consortium
Annual FOBT
Flex sig every 5 yrs
Combination of above
DCBE every 5 years
Colonoscopy every 10 years (preferred option – ACG)
Winawer Gastroenterology 2003;124:
American Cancer Society
Recommendations now identical to the GI consortium
Smith CA Cancer J Clin; 2004;54:41-52
One approach to colorectal screening guidelines is the so-called "menu of options". This approach was first presented in 1997 by a multidisciplinary consortium, sometimes called the "GI consortium". All of the options have acceptable and comparable cost-effectiveness, but they differ with regard to their upfront costs, risks, and effectiveness. The GI consortium guideline was revised in 2003, and since 1997, the American Cancer Society screening guidelines have been identical to those of the GI consortium. The menu of options approach is one that has been commonly endorsed in primary care practice. It provides the opportunity for physicians and patients to discuss the pros and cons of each option, and to have a greater chance of identifying an option that is acceptable to the patient.

12. Quantitative immunochemical FOBT
Improved detection of hemoglobin as compared to guaic based FOBT tests
Immunochemical FOBT testing uses antibodies to human globin expressed in colorectal bleeding.
94 % sensitivity for cancers and 67 % for advanced adenomas with approximate 90% sensitivity in high risk individuals (Ann Int Med 2007)
Has not yet been tested in asymptomatic average risk patients

13. A word about the digital rectal exam

16. Sigmoidoscopy Weaknesses
20-30 % of proximal advanced adenomas are missed with sigmoidoscopy
Sigmoidoscopy particularly poor in women missing 65 % of advanced polyps as opposed to colonoscopy (NEJM 2005)
Would you ever mammogram one breast ?

19. Screening Colonoscopy
Two large cohort studies (Winawer, et al, NEJM 1993 and Citarda, et al Gut 2001) have demonstrated significant reductions in colon cancer incidence if colonoscopy with polypectomy are performed
FOBT and sigmoidoscopy that lead to colonoscopy with polypectomy have been shown to significantly reduce colorectal cancer mortality

23. Screening colonoscopy
Combines the most complete examination of the colon with the direct therapy of removing dysplastic polyps
The role of polyps as a precursor to cancer provides the rationale for endoscopic screening illustrated by the benefit of adenoma removal by polypectomy at the time of colonoscopy

24. Novel and Emerging Advances in Colorectal Cancer Screening
CT colonography/Virtual colonoscopy
Fecal DNA analysis
Capsule endoscopy

25. CT colonography/Virtual colonoscopy
Computed tomography procedure that uses helical, multiple thin section images along with specialized computer programming to provide three-dimensional and two-dimensional images of the colon

27. Virtual Colonoscopy Quiz How many insurance carriers in the United States and internationally have approved CT colonography for colon cancer screening ?
Physicians Plus
Unity
Group Health

28. Virtual Colonoscopy - Sensitivity
Study
Patients
Polyps
6-9mm
Polyps > 10mm
Method
Profession of First Author
Pickhardt, et al NEJM
1233
88.8%
93.8%
3D Primary
Radiologist
Cotton, et al
JAMA
615
39.0%
55.0%
2D Primary
Gastro
Rockey, et al
Lancet
449
51.0 %
59.0%

29. Per Patient Analysis of Polyp Detection at UW
Virtual Colonoscopy
Program
N=1100
Colonoscopy
N=1079
P value
Total # of patients with polyps
120 (10.8%)
365 (33.8%)
P <
Patients with polyps > = 10 mm
43 (3.9%)
46 (4.3%)
P = 0.64
Patients with polyps 6-9 mm
77 (6.9%)
113 (10.5%)
P < 0.003
Patients with polyps < = 5 mm NR
287 (26.6%)

30. Advanced Adenoma Comparison
CTC
(n= 3,120)
Colonoscopy
(n = 3163)
Polyps removed
617
3, 016
P<0.001
Adenomas > 10 mm
103
P=0.92
Advanced neoplasms
123
121
P=0.81

31. Adenoma Comparison Virtual Colonoscopy Program N = 1110 Colonoscopy
P value
Total adenomas recovered 60
246
P <
Total advanced adenomas 32 43
P = 0.16
Advanced adenomas < 10 mm 4
P < 0.09

32. Physician
Cecal Intub.%
Intub.
time (min)
W/drawal time. Polyp
W/drawal time. No Polyp
W/drawal time
total
% pts w/ Ademona
Adenoma Det. Rate 1
100
8.1
14.0
9.0
12.5 37
.82 2
6.0
13.5
8.7
10.9 30
.73 3
7.9
12.7
9.6
10.7 25 4 98
5.7
9.8
4.3
7.0
.67 5 91
10.0
8.0 13
.43 6
7.2
4.5
5.6 21
.39 7
8.6
7.8
4.4 20
.26 8
8.9
5.5
3.4
4.0
.24 9
6.2
7.4 16
.23 10 95
8.4
5.4
.09 VC
.05
VC 43 patients > 10 ; 77 patients with 6-9 ; 65 concordant lesions seen on OC – 45 patients had at least one neoplastic lesion

33. Can you tell the difference between these polyps ?

35. Remember there is a person attached to every polyp

36. Fecal DNA Analysis
Colorectal cancer is a disease in which many DNA mutations associated with carcinogenesis have been characterized
Stool DNA is stable, shed continuously and through amplification tests can be detected in minute amounts
Most studied stool test for DNA mutations is a multicomponent test that targets point mutations at 15 “hot spots” on K-ras, APC, p53, Bat-26, and long DNA

37. Fecal DNA Analysis
Alquist, et al. Gastroenterology 2000 studied patients with colon cancers, large adenomas, and normal colons
Sensitivity of 91% for colon cancer, 82% for large adenomas and a specificity of 93%
Imperiale, et al. NEJM 2004 studied patients in a screening population
Poor sensitivity for invasive cancers (52%) and advanced polyps (15%)

38. M2A® Capsule Endoscope M2A captures images at 2 fps
More than 50,000 images are taken
Field of view: 140º
Min. detectable object: Less than 0.1 mm

39. Multiple telangiectasia on a gastric fold
Mouth to Cecum
Teeth
Epiglottis
Multiple telangiectasia on a gastric fold
c,d) approaching the pylorus
Small Intestine
Ileocecal valve
Wall of right colon

40. Summary – Colon Cancer Screening
FOBT, barium enema, sigmoidoscopy
All recommended but all with significant weaknesses
Will iFOBT make a come back ?
Screening Colonoscopy
Standard of care – Diagnosis along with therapy
CT colonography
Here today – Further verification using one technology in multicenter study and more importantly how CT colongraphy will work with standard colonoscopy
Fecal DNA analysis and Capsule Endoscopy
Here tomorrow – Further refinement and technical improvements needed

41. Screen your patient – PCP most important physician in colon cancer