1. Update on Colorectal Cancer Screening Tests Source: Levin Bernard et al. Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA A Cancer Journal for Clinicians 58(3):130- 160, May/June 2008.

2. Colorectal Cancer America’s # 2 Cancer Killer America’s # 2 Cancer Killer

3. Expert Panel Opinion u Colorectal cancer prevention (not CRC mortality reduction) should be primary goal of CRC screening. u Tests designed to detect both early cancer and adenomatous polyps should be encouraged if resources available and patients willing to undergo test.

4. Testing Options for Early Detection of Colorectal Cancer and Adenomatous Polyps for Average-risk Women and Men Aged 50 Years and Older u Partial or full structural exams (invasive tests that detect adenomatous polyps and cancer) –Flexible sigmoidoscopy every 5 years –Colonoscopy every 10 years –Double-contrast barium enema every 5 years –Computed tomographic colonography every 5 years u Fecal tests with high test sensitivity* (noninvasive tests that primarily detect cancer) –Annual guaiac-based fecal occult test (gFOBT) –Annual fecal immunochemical test (FIT) –Stool DNA test *Note: Expert panel does NOT recommend gFOBT testing in doctor’s office as a single-panel test following digital rectal exam.

5. Limitations and Requirements of Fecal Tests u Less likely to prevent cancer compared with invasive tests u Must be repeated at regular intervals to be effective u If abnormal, an invasive test (colonoscopy) will be needed

6. Stool DNA Test New Recommended Test

7. Colorectal cancer A series of genetic defects Normal Carcinoma 5q(APC) alterations K-RAS mutation 17p (p53) alterations Colonic epithelium Benign neoplasia Larger Tumor Malignant neoplasia 18q alterations Adenoma Advanced Adenoma

8. Stool DNA Test u Prototype assay of this test (version 1.0) –23 DNA markers assayed »21 point mutations in K-ras, APC, and p53 »1 microsatellite instability marker: BAT-26 »DNA Integrity Assay (DIA) –Minimum 30 grams of stool required –Specific for human DNA - diet not needed u Currently available assay (version 1.1) –Same DNA marker panel –Incorporates technical advances in processing and specimen preservation to increase test sensitivity

9. Stool DNA Screening Process Physician Sends Requisition to Lab Lab Provides Collection and Shipping Materials to Patient Patient Collects Stool at Home Patient Returns Specimen to Lab Physician : Communicates Results to Patient Stool DNA Analysis Is Performed in Lab and Reported to DNA Alteration Identified Perform colonoscopy No DNA Alteration Identified Continue screening Ice Pack

10. Stool DNA Test Pros: u Noninvasive, private u No dietary restriction or cathartics u One specimen & no need to handle stool u Acceptable sensitivity u High acceptance by patient and provider u Detects other cancers Cons: u Sensitivity less than colonoscopy u Cost high relative to FIT or gFOBT u Performance intervals unknown u Cost-effectiveness needs further study u Panel of markers identifies majority, but not all, of CRC u Significance of positive test result in patient with negative follow-up evaluation unknown

11. Stool DNA Test Key Issues for Informed Patient Decisions u Adequate stool sample must be obtained and packaged with appropriate preservative agents in shipping to laboratory u Unit cost of currently available test significantly higher than other forms of stool testing (e.g., $575 – DNAdirect Genetic Testing Online) u If test positive, colonoscopy recommended u If test negative, appropriate interval for repeat test uncertain (manufacturer recommending 5-year interval)

12. Virtual Colonoscopy or CTC (Computed Tomographic Colonography) New Recommended Test u Minimally invasive CT imaging examination of the entire colon and rectum u Adequate bowel prep and gaseous distention of colorectum essential to quality exam u Uses advanced 2-dimensional and 3-dimensional image display techniques for interpretation u Since introduction in mid-1990s, rapid advancements in CTC technology have occurred

13. CT-scanner for Virtual Colonography Colonoscopy View Virtual Colonography View

14. Virtual Colonoscopy or CTC Pros: u Time-efficient procedure u Good accuracy u Minimal invasiveness u No sedation or recovery time u Patient can return to work same day u Potential for same day colonoscopy u Detection of non-GI abnormalities Cons: u Reimbursement for screening CTC currently limited u Professional capacity to deliver limited u Requires bowel prep u Quality of interpretation highly operator dependent u Controversy over radiation dose effects u Relatively expensive ($400 - $800)

15. Virtual Colonoscopy or CTC Key Issues for Informed Patient Decisions u Complete bowel prep required u If patient has one or more polyps >= 6 mm, colonoscopy recommended; if same day colonoscopy not available, second complete bowel prep required u Risks are low; rare cases of perforation reported u Extracolonic abnormalities may be identified

16. Summary Colorectal Cancer Screening Report from Expert Panel u Promote colorectal cancer prevention as primary goal u Endorses two new screening tests – Stool DNA and CTC u Recommends fecal tests with high test sensitivity