Transcript Advances in the Surgical Treatment of Colorectal Cancer

Benefits of Screening
Colonoscopy
Colorectal Cancer
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The third most common cancer in the U.S.
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148,810 new cases expected in 2008
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The second deadliest cancer
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49,960 deaths nationwide
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More than 1 million Americans living with colorectal cancer
Colorectal Cancer Risk Factors
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Age
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Gender
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Slight male predominance, but common in both men and women
Race/Ethnicity
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90% of cases occur in people 50 and older
African Americans have highest incidence and mortality rate of all groups in U.S.,
Hispanics the lowest (with considerable variation depending on country of origin)
Increased rates also documented in Alaska Natives, some American Indian tribes,
Ashkenazi Jews
Increased risk with:
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Personal history of inflammatory bowel disease, adenomatous polyps, colon cancer,
other conditions
Colorectal Cancer
Sporadic (average risk)
(65-85%)
Family History (10-30%)
Hereditary nonpolyposis
colorectal cancer (HNPCC)
(5% )
Familial adenomatous
polyposis (FAP) (1%)
Rare syndromes (<0.1%)
Risk Factors - Polyps
Different types
• Hyperplastic
 Minimal cancer potential
• Adenomatous
 Approximately 90% of colon and
rectal cancers arise from
adenomas
Normal to
Adenoma to
Carcinoma
Human colon carcinogenesis
progresses by the dysplasia/adenoma
to carcinoma pathway
Benefits of Screening
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Cancer Prevention
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Removal of pre-cancerous polyps prevent cancer
(unique aspect of colon cancer screening)
Improved Survival
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Early detection markedly improves chances of long
term survival
5-year Survival
Benefits of Screening
100
90
80
70
60
50
40
30
20
10
0
89.8%
Survival Rates by Disease Stage
67.7%
10.3%
Local
Regional
Stage of Detection
Distant
Colorectal Screening Rates
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Just 40% of colorectal cancers are detected at
the earliest stage
A little more than half of Americans over age 50
report having had a recent colorectal cancer
screening test
Slow but steady improvement in these numbers
over the past decade (but all are not benefiting
to the same degree)
Prevalence (%)
Trends in Recent Endoscopy Prevalence (%) by
Educational Attainment and Health Insurance Status,
Adults 50 Years and Older, US, 1997-2004
50
45
40
35
30
25
20
15
10
5
0
1997
1999
2001
2002
2004
Total
Less than high
school education
No health
insurance
Colorectal Stage vs Insurance
30
Percentage
25
20
Private
Uninsured
Medicaid
15
10
5
0
1
2
3
4
CRC Screening Guidelines
What’s New?
CRC screening tests are grouped into two categories:
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Tests that detect cancer and precancerous polyps
Tests that primarily detect cancer
* It is the strong opinion of the consensus guidelines group that colon
cancer prevention should be the primary goal of CRC screening.
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Exams that are designed to detect both early cancer and precancerous polyps
should be encouraged if resources are available and patients are willing to undergo
an invasive test
If the full range of screening tests are not available, physicians should make every
effort to offer at least one test from each category
CRC Screening Guidelines
What Else is New?
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Two new tests recommended:
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Stool DNA (sDNA) and
Computerized tomographic colonography (CTC)sometimes referred to as virtual colonoscopy
The guidelines establish a sensitivity threshold
for recommended tests
The guidelines delineate important qualityrelated factors for each form of testing
2008 CRC Screening Guidelines
Beginning at age 50, both men and women at average risk for developing
colorectal cancer should use one of the screening tests below:
Tests That Detect Adenomatous Polyps and Cancer
Flexible sigmoidoscopy (FSIG) every 5 years*, or
Colonoscopy every 10 years, or
Double contrast barium enema (DCBE) every 5 years*, or
CT colonography (CTC) every 5 years*
Tests That Primarily Detect Cancer
Annual guaiac-based fecal occult blood test (gFOBT) with high test sensitivity for
cancer*, **, or
Annual fecal immunochemical test (FIT) with high test sensitivity for cancer*, **, or
Stool DNA test (sDNA), with high sensitivity for cancer*, interval uncertain
*Colonoscopy should be done if test results are positive.
**For gFOBT or FIT used as screening test, the take-home multiple sample method should be used.
gFOBT or FIT done during a digital rectal exam in the doctor’s office is not adequate for screening.
CRC Screening Guidelines
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New recommendations provide information on
performance and quality issues related to each
form of testing.
An overriding goal of this update is to provide a
practical guideline for physicians and the public
Guidelines continue to emphasize options for
testing
2008 CRC Guidelines Continue to
Emphasize Options Because:
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Evidence does not yet support any single test as “best”
Uptake of screening remains disappointingly low
Individuals differ in their preferences for one test or another
Primary care physicians differ in their ability to offer, explain,
or refer patients to all options equally
Access is uneven geographically, and in terms of test charges
and insurance coverage
Uncertainty exists about performance of different screening
methods with regard to benefits, harms, and costs (especially
on programmatic basis)
If tests that an prevent CRC are preferred,
why not recommend them alone?
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Greater patient requirements for successful completion
Endoscopic and radiologic exams require a bowel prep and an office or
facility visit
No true “gold standard”
Colonoscopy misses 5-10% of significant lesions in expert settings
Higher potential for patient injury than fecal testing
Risk levels vary between tests, facilities, practitioners
Patient preference
Many individuals don’t want an invasive test or a test that requires a bowel
prep
Some prefer to have screening in the privacy of their home
Some may not have access to the invasive tests due to lack of coverage or
local resources
Quality Issues
2008 CRC Screening Guidelines
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The medical literature reflects quality concerns
related to essentially all forms of testing
Examples include:
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Inadequate flex sig insertion depth
Abbreviated colonoscopy withdrawal times
Poor sensitivity of in-office FOBT
FOBT Sensitivity:
Take Home vs In-Office
Sensitivity
FOBT method
(Hemoccult II)
All Advanced
Lesions
Cancer
3 card,
take-home
23.9%
43.9%
Single sample,
In-office
4.9%
9.5%
In-Office FOBT should be abandoned
Conclusion:
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In-office FOBT is essentially worthless as a screening tool for
CRC and must be strongly discouraged
However:
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In a recent national survey, nearly 30% of physicians reported
using single-sample, in-office FOBT as their primary method
of screening for colorectal cancer.
2008 CRC Screening Guidelines
New Tests
Stool DNA
Stool DNA Test (sDNA)
• Rationale
• Fecal occult blood tests detect
blood in the stool – which is
intermittent and non-specific
• Colon cells are shed continuously
• Polyps and cancer cells contain
abnormal DNA
• Stool DNA tests look for
abnormal DNA from cells that are
passed in the DNA
**all positive tests should be followed with colonoscopy
Genetic Model of Colorectal Cancer
Bat-26 (HNPCC)
APC
K-ras
Bat-26 (Sporadic)
p53
Mutation
Normal
Epithelium
Dwell Time:
Adenoma
Late
Adenoma
Early
Cancer
Many decades
2-5 years
2-5 years
Optimum phase for
early detection
Late
Cancer
sDNA – Sample Collection
sDNA – Sample Collection
Collection
bucket
inserted into
bracket and
installed
under toilet
seat
Patient
supplies
whole stool
sample; no
diet or
medication
restrictions
Patient seals
sample in
outer
container and
freezer pack
Patient seals
container and ships
back to designated
lab (all packing
materials and labels
supplied)
Performance Characteristics of Stool
DNA in the Detection of CRC
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Three versions of the previously marketed
sDNA test have been evaluated
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Version 1 (K-ras, APC, p53, BAT-26, DIA) was evaluated
in the Imperiale trial
Version 1.1 (K-ras, APC, p53), PreGen-Plus is the
currently marketed test
Version 2 (Vimentin only, or Vimentin + DIA)
Earlier and more recent tests were evaluated in
smaller, mixed populations
Performance Characteristics of Stool
DNA in the Detection of CRC
• Testing evaluates stool for the
presence of altered DNA in the
adenoma-carcinoma sequence
• No dietary restrictions
• No stool sampling (utilizes the
entire stool)
• Several studies suggesting strong
patient acceptance
• Testing interval uncertain
• Uncertainty about the meaning of
false positives
Study with OneTime Testing (v)
Sensitivity
For Cancer
Ahlquist, et al Gastro,
200 (1)
91%
Imperiale, et al NEJM,
2004 (1)
51.6%
Syngal, et al Cancer,
2006 (1)
63%
Whitney, et al J Mol
Diagn, 2004 (1)
70%
Chen, et al JNCI, 2005
(2)
46%
Itkowitz, et al DDWAB, 2006 (2)
88%
Stool DNA
Limitations
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Misses some cancers
Sensitivity for adenomas with current commercial version of test is low
Technology (and test versions) are in transition
Costs much more than other forms of stool testing (approximately $300$400 per test)
Not covered by most insurers
Appropriate re-screening interval is not known
Not clear how to manage positive stool DNA test if colonoscopy is negative
FDA issues
Test availability
CT Colonography (CTC)
CTC Image
Optical Colonoscopy
CT Colonography
Rationale
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Allows detailed evaluation of the entire colon
A number of studies have demonstrated a high level of
sensitivity for cancer and large polyps
Minimally invasive (rectal tube for air insufflation)
No sedation required
CT Colonography
2-D view
3-D view
Polyp
CTC Virtual “Fly Through”
CTC vs Optical Colonoscopy:
Sensitivities for Polyps > 5mm
Sensitivity
Study
Patients
Polyps
> 5mm
No. Per Polyp (%)
No. Per Patient
(%)
6-9mm
>10mm
6-9mm
>10mm
Boston
University,
Fenton et al
100
58
36 (82)
22 (91)
--- (92)
--- (96)
Mayo Clinic,
Fletcher et al
180
263
142 (47)
121 (75) --- (88)
--- (85)
UCSF, Yee et al
300
223
141 (80)
82 (90)
(93)
(100)
CTC vs Optical Colonoscopy
Meta-Analyses
Polyp Size
CTC
performance
> 10mm
6-9mm
Cancer
Pooled
Sensitivity
85-93%
70-86%
85.7%
Pooled
Specificity
97%
86-93%
----
CTC vs Optical Colonoscopy:
Sensitivities for All Polyps
Polyp Size
>10mm
>8mm
>6mm
CTC
92.2%
92.6%
85.7%
Colonoscopy
88.2%
89.5%
90.0%
CTC – Extra-Colonic Findings
Most have limited clinical impact, but some are
important:
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Asymptomatic cancers outside of colon and rectum
Aortic aneurysms
Renal and gall bladder calculi
CT Colonography
Limitations
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Requires full bowel prep (which most patients find to be the most
distressing element of colonoscopy)
Colonoscopy is required if abnormalities detected, sometimes necessitating
a second bowel prep
Steep learning curve for radiologists
Limited availability to high quality exams in many parts of the country
Most insurers do not currently cover CTC as a screening modality
Extra-colonic findings can lead to additional testing (may have both
positive and negative connotations)
Questions regarding:
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Significance of radiation exposure
Management of small polyps
Comparison of
Recommendations
Screening Method
ACS/USMSTF/ACR
USPSTF
Stool Testing
Guaiac based FOBT (gFOBT)
Annual screening with high sensitivity
guaiac based tests
Annual screening with high sensitivity
guaiac tests
Immunochemical-based FOBT (FIT)
Annual screening
Annual screening
Stool DNA (sDNA)
sDNA is an acceptable option
Insufficient evidence to recommend for or
against sDNA
Flexible Sigmoidoscopy
Screening every 5 years. Screening every
5 years, with annual gFOBT or FIT is an
option
Screening every 5 years, with gFOBT
every 3 years
Colonoscopy
Screening every 10 years
Screening every 10 years
CT Colonography
Screening every 5 years
Insufficient evidence to recommend for or
against CT Colonography
Double Contrast Barium Enema
(DCBE)
Screening every 5 years
Not addressed
The 2008 CRC Guidelines Update
was a Joint Effort of 5 Organizations
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American Cancer Society
U.S. Multi-Society Task Force on Colorectal
Cancer
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American Gastroenterological Association
American College of Gastroenterology
American Society of Gastrointestinal Endoscopists
American College of Radiology