Update on Colorectal Cancer Screening Tests

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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.
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Colorectal Cancer
Americas 2 Cancer Killer

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Expert Panel Opinion

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

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Testing Options for Early Detection of Colorectal
Cancer and Adenomatous Polyps for Average-risk
Women and Men Aged 50 Years and Older

• 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
• 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 doctors office as a single-panel
test following digital rectal exam.
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Limitations and Requirements of Fecal Tests

• Less likely to prevent cancer compared with
  invasive tests
• Must be repeated at regular intervals to be
  effective
• If abnormal, an invasive test (colonoscopy) will
  be needed

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Stool DNA TestNew Recommended Test
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Colorectal cancerA series of genetic defects
5q(APC) alterations
K-RAS mutation
17p (p53) alterations
18q alterations
Carcinoma
Advanced Adenoma
Normal
Adenoma

Colonic epithelium
Benign neoplasia
Larger Tumor
Malignant neoplasia
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Stool DNA Test

• 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
• Currently available assay (version 1.1)
• Same DNA marker panel
• Incorporates technical advances in processing and
  specimen preservation to increase test sensitivity

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Stool DNA Screening Process
Physician
Stool DNA Analysis Is Performed in Lab and
Reported to
Patient Collects
Sends
Stool at Home
Requisition
to Lab
Physician
Ice Pack
Lab Provides
Patient Returns
Physician Communicates Results to Patient
Collection and
Specimen to Lab
DNA Alteration Identified Perform colonoscopy
Shipping Materials
to Patient

No DNA Alteration Identified Continue screening
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Stool DNA Test

• Pros
• Noninvasive, private
• No dietary restriction or cathartics
• One specimen no need to handle stool
• Acceptable sensitivity
• High acceptance by patient and provider
• Detects other cancers

• Cons
• Sensitivity less than colonoscopy
• Cost high relative to FIT or gFOBT
• Performance intervals unknown
• Cost-effectiveness needs further study
• Panel of markers identifies majority, but not
  all, of CRC
• Significance of positive test result in patient
  with negative follow-up evaluation unknown

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Stool DNA TestKey Issues for Informed Patient
Decisions

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

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Virtual Colonoscopy or CTC (Computed Tomographic
Colonography)New Recommended Test

• Minimally invasive CT imaging examination of the
  entire colon and rectum
• Adequate bowel prep and gaseous distention of
  colorectum essential to quality exam
• Uses advanced 2-dimensional and 3-dimensional
  image display techniques for interpretation
• Since introduction in mid-1990s, rapid
  advancements in CTC technology have occurred

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CT-scanner for Virtual Colonography
Colonoscopy View
Virtual Colonography View
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Virtual Colonoscopy or CTC

• Pros
• Time-efficient procedure
• Good accuracy
• Minimal invasiveness
• No sedation or recovery time
• Patient can return to work same day
• Potential for same day colonoscopy
• Detection of non-GI abnormalities

• Cons
• Reimbursement for screening CTC currently limited
• Professional capacity to deliver limited
• Requires bowel prep
• Quality of interpretation highly operator
  dependent
• Controversy over radiation dose effects
• Relatively expensive (400 - 800)

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Virtual Colonoscopy or CTCKey Issues for
Informed Patient Decisions

• Complete bowel prep required
• If patient has one or more polyps 6 mm,
  colonoscopy recommended if same day colonoscopy
  not available, second complete bowel prep
  required
• Risks are low rare cases of perforation reported
• Extracolonic abnormalities may be identified

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Summary

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