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