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.

Colorectal Cancer

America’s# 2

CancerKiller

America’s# 2

CancerKiller

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.

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 doctor’s office as a single-panel test following digital rectal exam.

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

Stool DNA TestNew Recommended Test

Colorectal cancerA series of genetic defects

NormalNormal CarcinomaCarcinoma

5q(APC)alterations

K-RASmutation

17p (p53)alterations

Colonic epithelium

Benignneoplasia

LargerTumor

Malignantneoplasia

18q alterations

Adenoma AdvancedAdenoma

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

Stool DNA Screening Process

PhysicianSends

Requisitionto Lab

Lab ProvidesCollection and

Shipping Materialsto Patient

Patient CollectsStool at Home

Patient ReturnsSpecimen to Lab

Physician

:

PhysicianCommunicates

Results to Patient

Stool DNA AnalysisIs Performed in Lab

and Reported to

DNA AlterationIdentified

Perform colonoscopy

No DNA AlterationIdentified

Continue screening

Ice Pack

Stool DNA TestPros: 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

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)

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

CT-scanner for Virtual Colonography

ColonoscopyView

VirtualColonography

View

Virtual Colonoscopy or CTCPros: 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)

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

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