update on colon cancer screening and prevention patrick r. pfau, m.d., university of wisconsin...
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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
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
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
Adherence Rates – Cancer Screening
U.S. Adherence Rates
Breast Cancer 69% *
Cervical Cancer 86% *
Prostate Cancer 75%**
Colorectal Cancer 45% * 63%**
* Seeff Cancer 2002;95:2211-22
**Sirovich JAMA 2003;289:1414-20
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)
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;124:544-560
American Cancer Society
• Recommendations now identical to the GI consortium
– Smith CA Cancer J Clin; 2004;54:41-52
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
A word about the digital rectal exam
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 ?
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
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
Novel and Emerging Advances in Colorectal Cancer Screening
• CT colonography/Virtual colonoscopy
• Fecal DNA analysis
• Capsule endoscopy
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
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
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
JAMA615 39.0% 55.0% 2D
Primary
Gastro
Rockey, et al
Lancet
449 51.0 % 59.0% 2D Primary
Gastro
Per Patient Analysis of Polyp Detection at UW
Virtual Colonoscopy
Program
N=1100
Colonoscopy
Program
N=1079
P value
Total # of patients with
polyps
120 (10.8%) 365 (33.8%) P < 0.0001
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%) P < 0.0001
Advanced Adenoma Comparison
CTC
(n= 3,120)
Colonoscopy
(n = 3163)
Polyps removed
617 3, 016 P<0.001
Adenomas > 10 mm
103 103 P=0.92
Advanced neoplasms
123 121 P=0.81
Adenoma ComparisonVirtual
Colonoscopy
Program
N = 1110
Colonoscopy
Program
N = 1079
P value
Total adenomas recovered
60 246 P < 0.0001
Total advanced adenomas
32 43 P = 0.16
Advanced adenomas <
10 mm
0 4 P < 0.09
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
2 100 6.0 13.5 8.7 10.9 30 .73
3 100 7.9 12.7 9.6 10.7 25 .73
4 98 5.7 9.8 4.3 7.0 30 .67
5 91 9.8 10.0 7.0 8.0 13 .43
6 100 7.0 7.2 4.5 5.6 21 .39
7 100 8.6 7.8 4.4 5.6 20 .26
8 100 8.9 5.5 3.4 4.0 21 .24
9 98 9.8 9.8 6.2 7.4 16 .23
10 95 9.6 8.4 5.4 6.2 7 .09
VC 4 .05
Can you tell the difference between these polyps ?
Remember there is a person attached to every polyp
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
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%)
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
Mouth to Cecum
Teeth EpiglottisEpiglottis
Small IntestineSmall Intestine Ileocecal valveIleocecal valve Wall of right colonWall of right colon
Multiple telangiectasia on Multiple telangiectasia on a gastric folda gastric fold
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
•Screen your patient – PCP most important physician in colon cancer