Prevention and Early Detection

of Colorectal Cancer

America’s
#2
Cancer
Killer
A presentation sponsored by
Iowa Colorectal Cancer Screening Task Force
American Cancer Society

This presentation, “Prevention and Early Detection of Colorectal Cancer”, was

developed by Dr. Robert Summers, Professor of Internal Medicine and
Gastroenterology at the University of Iowa as an education program directed to
the interests of health care professionals. It was sponsored by the Iowa
Colorectal Cancer Task Force and the American Cancer Society.

1
 Prevention and Early Detection
of Colorectal Cancer

America’s
#2
Cancer
Killer

Message: You Can Stop this Killer by

Integrating Screening Into Your Practice!

Only lung cancer kills more people each year than colorectal cancer. The main
message of this talk is that this ugly picture of colon cancer can be wiped out
with an integrated screening program in your medical practice.
The key to saving lives is prevention and early detection. This approach is far
more important than treating the disease after it has occurred.

2
 Prevention
• Environmental factors can be modified to
prevent or reduce the occurrence of CRC
– Increase exercise
– Reduce obesity
– Calcium
– Vitamin D
– NSAIDs
• May be a very important strategy in future

Epidemiologic and experimental trials have shown that the risk of developing
colon polyps and colorectal cancer can be reduced through the use of diet and
dietary supplements. The benefits are currently quite modest. The discovery
of more effective treatments may make this a viable option for developing a
prevention strategy in the future. However at present, we can not rely on these
preventive measures for control of colon cancer.

3
 Outline of Talk
• Epidemiology and natural history
• The case for screening
• Recommended screening tests
– Fecal occult blood tests (FOBT)
– Flexible sigmoidoscopy
– Double contrast barium enema (DCBE)
– Colonoscopy
• New tests on the horizon-virtual colonoscopy,
genetic testing, stool DNA
• Summary/Conclusions

In this talk, we will be discussing some of the background material that

provides a means of diagnosing early and highly curable lesions. The case for
providing early screening is very strong and the slides will outline the common
and effective clinical tests that are available. We will discuss:
Epidemiology and natural history
The case for screening
Recommended screening tests
Fecal occult blood tests (FOBT)
Flexible sigmoidoscopy
Double contrast barium enema (DCBE)
Colonoscopy
New tests on the horizon-virtual colonoscopy, genetic testing, stool DNA
Summary/Conclusions

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 Colorectal Cancer: Epidemiology
(The bad news):
•Incidence: (in 2006)
•148,610 new cases will be diagnosed in U.S.
•Lifetime risk is 6% (1 in 18)
•Deadly:
•Second leading cause of cancer deaths
•55,170 deaths/yr; 5-year mortality 33%
•Expensive:
•The most costly cancer to treat

First, the bad news! CRC is very common and nearly 150,000 new cases will
be diagnosed this year. It occurs in 6% of the population and the lifetime risk
of developing the disease is 1 in 18. This is a number that shocks most people.
Furthermore, more than 33% of these or 55,170 people died from the disease in
2006.

5
 Colorectal Cancer: Epidemiology

(The good news)

• If detected early, 91% 5-year relative
survival rate (adjusted for normal life
expectancy)
• The most preventable form of
visceral cancer if screening is
performed

And now, the good news! There is a very high survival and cure rate if colon
cancer is detected early and most cancers can be prevented by removal of pre-
malignant adenomatous polyps.

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 Natural History: Polyp to Cancer

Normal Adenoma Carcinoma

Ten years allows time to intervene

A series of molecular events transforms normal colonic epithelieal cells into

adenomatous polyps and then into colon cancer. This process takes ten years,
thus there is time to intervene. Screening examinations which lead to the
removal of polyps can prevent this process.

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 Risk Factors for Colorectal Cancer
Average Risk
>50 years old, asymptomatic High-Risk Cases
High Risk
25%
FAP
HNPCC
75%
IBD
Personal or 10 relative
with CRC or Adenomas Average-Risk Cases
American Cancer Society. Cancer Facts & Figures 2002. Atlanta, GA: American
Cancer Society; 2002:20 27.

Patients who are over 50 and have no symptoms are considered to be at

average-risk and they constitute the majority (75%) of colon cancer cases.
Patients who are members of families with familial polyposis (FAP),
hereditary non-polyposis colon cancer (HNPCC), who have inflammatory
bowel disease (IBD) or have a personal or family history of adenomas or
colorectal cancer are considered to be at high risk of developing colon cancer.
Persons at high risk have a 1 in 5 chance of developing colon cancer, however,
they account for only 25 % of colon cancer cases.

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 Colorectal Cancer Screening
• Compelling rationale
– Early detection and treatment proven to
decrease in cancer-related mortality
• Suitable and effective tests
– Are widely available
• Favorable cost-effectiveness
– Removal of polyps prevents invasive
cancer and saves money

• So, what’s the problem?

It is important to define what we are talking about.

Screening - Testing asymptomatic persons with no prior history of neoplasia
Surveillance - Follow-up testing of high risk patients with prior history of
adenomas, cancer, or pan-colitis
Diagnostic - Testing when there is a need to investigate symptoms such as
bleeding, pain, or altered bowel habits
Screening is the most important category because it is where we can have the
greatest impact on reducing deaths from colon cancer.

There are several important reasons to consider doing colorectal cancer

screening.
Compelling rationale
Early detection and treatment have been proven to decrease cancer-
related mortality
Suitable and effective tests
Are widely available
Favorable cost-effectiveness
Removal of polyps prevents invasive cancer and saves money
So, what is the problem?

9
 The U.S. population is not being
screened!

• Only 26% of the eligible population have

had a FOBT in the past 3 years
• Only 33% have ever had a FOBT
• Approximately 60% of the eligible US
population are never screened for CRC

2004 Behavior Risk Factor Surveillance System {database}

Atlanta Centers for Disease Control and Prevention; 2004

The U.S. population is not being screened for colorectal cancer.

Only 26% of the eligible population have had a FOBT in the past 3 years
Only 33% have ever had a FOBT
Approximately 60% of the eligible people in the US are never screened for
CRC

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 U.S. CRC Screening Rates
How is Iowa Doing?

Iowa is not the best or worst, but we can do better

2004 Behavior Risk Factor Surveillance System {database}
Atlanta Centers for Disease Control and Prevention; 2004

How are we doing in the state of Iowa?

According to the CDC, only about 52% of eligible Iowans are being screened
for colorectal cancer. Thus, we are neither the best nor the worst, but no one
is doing an adequate job and we can do better.

11
 Early Detection Saves Lives
5-Year Relative Survival Rates* for Iowa Patients
Diagnosis With CRC Between 1995-2001
100% 96%
100 84% 100
65%
75 75
50 50
25 25
8%
0 0
Stage 0 Stage I Stage II Stage III Stage IV
(Dukes’ A) (Dukes’ B) (Dukes’ C) (Dukes’ D)
Early Diagnosis: Late Diagnosis:
60% of 40% of
Patients Patients
SEER*Stat -- Version 6.2.4
* Adjusted for normal life expectancy

This slide shows the 5 year survival of Stages 0, I, and II cancer to be greater
than 80%. Unfortunately, only 60% of cancers are diagnosed at these stage.
40% of cancers are diagnosed at Stages III or IV where survival is dismal, at
less than 65%. Screening either prevents the problem or makes the diagnosis
at earlier stages before symptoms arise.

12
 Why aren’t patients screened?

• The most common reasons -

• “My doctor never told me I should be screened.”
• “I’m embarrassed!”
• “The screening tests cost too much!”
• “I don’t think that insurance covers screening.”
• “I don’t have a family history of colorectal cancer.”
• “I don’t have any symptoms of colorectal cancer.”
• Therefore, we must recommend screening and
help our patients dispel the limitations of
understanding, fear and embarrassment
2004 Iowa Behavior Risk Factor Surveillance System {database}
Iowa Department of Public Health; 2004

Why aren’t patients screened?

The most common reasons -
Only about half of patients surveyed said their health care professional
ever talked about screening.
Of those offered to be screened, 75% say they get the test.
Therefore, we must recommend screening and help our patients dispel
the limitations of understanding, fear and embarrassment.
Comment: Colon screening requires colonic cleansing which can cause
discomfort. However, newer preparations for the procedure and the use
of conscious sedation minimizes these problems and the procedure is
very well tolerated by the vast majority of patients.
In addition, some people are not screened until age 65, because they
wait to be covered by Medicare before getting screened.

Although a test should not be done to merely avoid medical-legal liability, it

should be noted that successful suits are being brought for:
•Failure to evaluate rectal bleeding
•Failure to investigate (+) FOBT
•Failure to recommend screening

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 Age Distribution of Colorectal Cancer (In Situ and Malignant),
Males and Females Combined, Iowa, 2000-2003
(N=8,509)

25% have 74% after

Polyps @ 50 Age 65+

•Reduce mortality
•Detect/resect curable cancers (Dukes A/B), before advanced
life-threatening disease
• Reduce incidence
•Identify/eradicate/prevent premalignant benign adenomatous
polyps
•Improve risk management
•It is becoming increasingly difficult to defend failure to screen or
diagnose CRC
•It is the standard of care !

This is the age distribution of the occurrence of colorectal cancer in Iowa

during the last decade. It shows that 94% of cases are diagnosed after age 50
and 74% after age 65. BUT 25% of those screened will have a polyp at age
50! This is one of the reasons why screening in the average risk population is
recommended to begin at age 50

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 Recommended CRC Screening Strategies:
Average risk (ACS, AGA, ACG Guidelines)

Options beginning at age 50 years:

• Annual fecal occult blood testing (FOBT) or
• Flexible sigmoidoscopy (FS) every 5 years, or
• Annual FOBT + FS every 5 years or
• Double -contrast barium enema every 5 yrs.,
• Colonoscopy every 10 yrs.
The only unacceptable option is NOT to screen
Digital rectal exam is not an appropriate screening method
Winawer S et al. Gastroenterology 2003: 124:544-560

These are the recommended screening strategies for the average risk patient by
the American Cancer Society, the American Gastroenterological Association
and the American College of Gastroenterology.
•Annual fecal occult blood testing (FOBT) or
• Flexible sigmoidoscopy (FS) every 5 years, or
• Annual FOBT + FS every 5 years or
• Double -contrast barium enema every 5 yrs.,
• Colonoscopy every 10 yrs.
The only unacceptable option is NOT to screen
Digital rectal exam is not an appropriate screening method

15
 Coverage for average risk
Medicare patients
• Screening with annual FOBT and
sigmoidoscopy are allowed every 4 yrs
• Direct colonoscopic screening is allowed
every 10 yrs
• Barium enema may be used as an
alternative to either sigmoidoscopy or
colonoscopy and is allowed every 5 yrs
(since July 1, 2001)

Since 2001, colorectal cancer screening is covered by Medicare. It is also

covered by most insurance carriers and HMOs. The procedures covered
include:
•Screening with annual FOBT and sigmoidoscopy are allowed every 4 years
• Direct colonoscopic screening is allowed every 10 years
• Barium enema may be used as an alternative to either sigmoidoscopy or
colonoscopy and is allowed every 5 yrs
Although Medicare covers colorectal cancer screening, a person should not
wait until age 65 (when Medicare coverage begins) to seek screening. Most
insurance providers cover some, if not all costs of screening. Patients should
consult their insurance plan or provider for more information.

16
 Fecal Occult Blood Testing

Winawer 2001

0.8 Control
0.7 Screened
0.6 But
0.5
Only
0.4
0.3
About
CRC Mortality/10 yr. (%) 10-20%
0.2
0.1
0
England Denmark Minnesota

Fecal occult blood testing is a simple chemical test to detect minute amounts of
blood in the stool. A positive test is not specific for colon cancer, but it
requires a diagnostic evaluation involving an examination of the colon in most
situations. Fecal occult blood testing requires three consecutive stools. It is
OK to do on rectal exam and if on coumadin or ASA. If the patient with a
positive test has had a diagnostic colonic exam in a reasonable time prior to the
test, it is usually not necessary to repeat a barium enema or colonoscopy to
evaluate for colon cancer.

Annual hemoccult testing reduces mortality from colon cancer if and only if
appropriate follow-up testing is done. Each of these studies shown in the
graph on the right side of the slide shows a statistically significant reduction in
mortality showing that FOBT is an appropriate and accepted screening test.
However, the reduction is only about 10-20% and other screening tests may be
provide greater benefit.

17
 Pros and Cons of FOBT
Pros: Cons:
• Evidenced based, • Limited effectiveness
finds most cancers, • Requires annual testing
reduces mortality • Patient role may be
• Non-invasive considered distasteful
• No bowel prep • Dietary restrictions used
• Easy to perform, • High rate of false
widely available negatives and positives
• Cost-effectiveness • Requires proper response
is established by PCP, investigate (+) !
Rex DK Rev Gastroenterol Disord. 2002

See slide

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 Flexible Sigmoidoscopy

Flexible sigmoidoscopy allows direct visualization of the lower 1/3 of the

rectum and colon. It can be performed with minimal preparation and usually
does not require sedation. If a polyp or cancer is detected, then the entire colon
must be examined by a full colon examination, usually colonoscopy so that a
polypectomy or biopsy can be performed.

The VA cooperative study ( NEJM 2000; 343:162) showed

the following data. 68% of advanced neoplasms (large polyps or cancers) were
detected with flexible sigmoidoscopy. This means that either the cancer, polyp
or other abnormality was seen that led to a further examination of the entire
colon and discovery of the neoplasm. Also, when combined with FOBT, the
yield improved further to 76%. This is a pretty good pickup rate, but it must
be recognized that sigmoidoscopy as a screening test misses about 1 of 4
cancers.

19
 Flexible sigmoidoscopy
Pros: • Cons:
• Office based • No sedation = discomfort
• Easy prep • Limited insertion to L colon
• Primary care MD’s • Miss rates are higher than
PA’s & RN’s can do BE/colonoscopy, especially
right side
• No sedation
• Finding polyps requires follow-
• Very cost effective up colonoscopy for removal
• (can have same day • 40% of CRC in R colon
colonoscopy)
• 50-80% reduction of
left-sided CRC’s

See slide

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 Double Contrast Barium Enema

“Apple Core”
Lesion

The double contrast barium enema is a time-honored test. It allows coating of

the wall of the colon with contrast (liquid containing barium that is consumed
prior to the test) and when distended with air, it provides a very good image of
the entire colon.

21
 Double Contrast BE
Pros: Cons:
• Safe • Requires bowel prep
• Low cost • Not studied adequately
• Cost effective • Missed 50% adenomas <
• Full colon exam 1cm, better if > 1cm
• High rate of • Sensitivity for pts. with
reimbursement
(+)FOBT is 50-70%
• Readily available,
seldom used, no • Tolerance/expertise decr.
randomized trials • Colonoscopy must be
done if a polyp is found

See slide
Unfortunately, with the advances in radiologic imaging, the interest and “art”
of doing a really good barium enema is disappearing.

22
 Combination

Double contrast barium enema

plus flexible sigmoidoscopy is
a reasonably good alternative
when colonoscopy is not available

Although this combined approach has not been tested, it is likely a good
screening tool when colonoscopy is not readily available. It can require two
preparations and does not offer a therapeutic option. A lesion seen on X-ray
requires colonoscopy for biopsy or removal. However, it does examine the
entire colon.

23
 Colonoscopy

The most effective weapon

against colon cancer currently available

Colonoscopy is the most effective weapon against colon cancer

currently available

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 Benefits of Colonoscopy

Can examine Can remove Can biopsy

entire colon adenomas carcinomas

It examines the entire colon and rectum and is highly effective. A typical
tubular adenoma on a stalk is seen in the middle photo and an invasive
carcinoma is shown on the right. The procedure requires a vigorous prep and
conscious sedation, but offers therapeutic options.

Lieberman,
How good is colonoscopy? The VA Colonoscopy Trial (

2001) examined the power of colonoscopy

versus flexible sigmoidoscopy (FS) and
fecal occult blood test (FOBT):
•2885 patients had FOBT and colonoscopy
•Of advanced adenomas, 23% had (+) FOBT
•FS found 70% of advanced adenomas, FS + FOBT found 76%
•Of adv. adenomas were missed by FS - 52% were proximal (asc. & trans.
colon)
•Conclusion: Colonoscopy screening is superior to FS or FS + FOBT

25
 Colonoscopy
Pros: Cons:
• Highest accuracy • Requires bowel prep
• Diagnostic and • Highest up front costs
therapeutic • Not always available
• Sedation leads to • Highest risk of all tests
willingness to repeat (complications 1:2000)
• Cost effective in • How feasible as a
comparison to other national strategy?
tests.

See slide text

26
 Do we have the Capacity?

• 14.2 million colonoscopies performed in 2002

• Direct colonoscopy screening of those over age
50 would require up to 2.6 million more
procedures per year -Total - 16.8 million
• Surveys in Iowa suggest that we have adequate
resources

Rex and Lieberman, 2001

Seeff, Richards, Shapito, Nadel, Manninen, Given, et al., 2004

Do we have the capacity to screen everyone over age 50? A recent study done
by the Iowa Department of Public Health suggests that we do have adequate
resources. In most communities, the waiting time to perform a screening
colonoscopy is about one month.

27
 Colonoscopy: Modify Indications
To Increase Availability
25
(Reduce frequency) (FS acceptable)
BRBPR
20

Polyp surveillance Pain (Low yield)

15

(Do More) (+)FOBT Constipation

10 Diarrhea

Anemia FS/BE IBD

5
Screen

0
(+)FHx Cancer .
Surveillance CORI: National Endoscopic Database, 2000-2001

One way we can increase the capacity for screening colonosocpy is to look
carefully at the indications. The common indications for doing colonoscopy
(Nat’t Endoscopy Data Base) are shown here. Those indications with a blue
background are entirely appropriate and should be continued, but those with
red backgrounds should be reduced. Although polyp surveillance is important,
the current guidelines should be followed and they recommend longer intervals
between tests. Flexible sigmoidoscopy is adequate for most patients with
hematachezia. Colonoscopy for pain and constipation is a low yield test and
other approaches should be considered in evaluating such patients.

The main point is that more screening capacity would be obtained by

reducing or eliminating colonoscopy use for reasons listed in red.

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 How Does One Decide Which
Patients to Test?

• First, take a detailed family history

• Determine whether siblings, parents, uncles or
aunts, grandparents had colon cancer or polyps
• At what age and where did these cancers or
polyps (type of polyps) occur?
• Any non-GI cancers? (breast, uterine ovarian,
CNS tumors, other GI, GU)

It is critical to take a thorough family history.

29
 If There is a Family History of CRC,
The Screening Strategy is Different!
15-20 %
5%

Lynch et al. Cancer 2004

25% of cancers are clustered in several familial groupings noted in the slide.
These patients must be considered at high risk of developing colon cancer.
The most well known syndrome is familial adenomatous polyposis or FAP.
The largest group of patients includes patients with a family history of colonic
polyps or colon cancer. Another large and important group are those with
hereditary non-polyposis colon cancer otherwise known as Lynch syndrome.
However, as you can see there are increasing numbers of less well known
syndromes that have an increased risk of developing colon cancer, and it is
highly likely that additional familial syndromes will be discovered in the
future..
We do not have time to describe all of these syndromes, but several of them
are also at risk of developing other cancers and thus a detailed family history is
critical to recognize and manage these patients adequately.

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 What to do with a Family
History of Concern ?

• Consider genetic testing

• Obliged to test and counsel family
• If possible, find tumor for analysis
• Continue with screening if appropriate

It is increasingly important to consider genetic testing in patients who may in a

high risk family. It is also important to test and counsel the family members if
the testing is possible. If a previous tumor pathology specimen is available, it
can be very helpful in directing testing. If a familial syndrome is diagnosed,
screening procedures can be directed more specifically for members at high
risk.

31
 Screening of Individuals with a
Family History of CRC
• One first degree relative with CRC or
adenomatous polyp after age 60
– Low family risk - standard screening
beginning at age 40
• One first degree relative with CRC or polyps
before age 60, right side, multiple primaries,
multiple relatives with CRC or polyps
– High familial risk - colonoscopy every 1-2
years beginning at age 25
– There is a place for prophylactic colectomy

These are some screening principles for patients who have a positive family
history.

32
 How to Reduce Deaths due to
Colon Cancer

When all is said and done, our message is that screening can reduce deaths due
to colorectal cancer.

33
 Screening for CRC:
What should be done?
The present The future
Benefit is proven: Data dependent:
• FOBT • Virtual colonoscopy
• FS • Stool DNA testing
• FOBT + FS
• DCBE • Genetic testing
• FS + DCBE • Effective
• Colonoscopy Chemoprevention

At present, any of these six approaches on the left are accepted and
recommended screening strategies. They can reduce mortality and are cost
effective. In the future, the five approaches on the right may also be accepted
and recommended, but for several of them, the data supporting their use is
incomplete.

34
 What the Physician Considers
Test Sensitivity Specificity Cost Invasive
FOBT Low Low (Low) No
Flex sig Mod Mod Mod Yes
DCBE Mod Low Mod Yes
Colonoscopy High High High Yes
Virtual C’ High Low High No
Stool DNA Mod Mod High No
Ahlquist ‘2001

These are the factors that physicians consider in deciding on a screening

strategy for a patient. The best test should exhibit high sensitivity, high
specificity, low cost, and should not be invasive. At this time, colonoscopy is
considered the most sensitive and specific test available and its use is
increasing. However, availability and patient acceptability are additional
factors that enter into the decision of which test to choose for an individual
patient.

35
 What The Patient Considers
• Which test is most accurate?
• Which test is most convenient?
• Which causes the least discomfort, fear
or embarrassment?
• Cost-insurance, Medicare coverage?
• What do other people say about it?
• What does my doctor recommend?

The patient has other considerations and these must be considered when
choosing a screening test. However, it is essential to recognize that what other
people say about the test and what the patient’s physician recommends are
very important for the patient’s decision and response.

36
 What the Insurer Considers

Screening Test Estimated Charge

FOBT $10-30
FS $150-300
DCBE $250-500
Stool-based DNA test $600-800
CT colonography $800-1000
Video colonoscopy $600-1500

At this time, insurance coverage for screening is not universal in the state of
Iowa. The costs listed are for a single test and the recommended intervals vary
by the test. FOBT is an annual examination and its cost is relatively high
because of the false positives that require further testing. The screening
interval for colonoscopy is 10 years if no polyps are found.

Costs are different for each insurance provider, Medicare, and screening
provider. Patient should consult their insurance plan or provider to obtain full
details on cost and coverage of colorectal cancer screening tests.

37
 The Cost of NOT Screening

– Expense of cancer care

– Emotional costs for patients
– Missed opportunity for prevention
– Legal consequences for providers

There are significant costs involved if screening is NOT performed.

38
 The End

You can prevent colorectal cancer

by screening!

We hope that we have convinced you of the value of screening for colorectal
cancer. It is truly a life-saving procedure and should be an important element
of high quality and preventive patient care.

39
 Acknowledgements
• American Cancer Society
• Centers for Disease Control & Prevention
• Exact Sciences
• John Bond, MD, Univ. of Minnesota
• Douglas Rex, MD, Univ. of Indiana

Prepared by
Robert W. Summers, MD, Univ. of Iowa

40
Colorectal Cancer Web Links

www.cancer.org
www.ccalliance.org
www.preventcancer.org/colorectal
www.hopkinskimmelcancercenter.org
www.colorectal-cancer.net
www.cdc.gov/cancer/screenforlife/index.htm

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