Professional Presentation Short Final

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.

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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.

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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.

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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.

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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 premalignant 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

FAP HNPCC IBD Personal or 10 relative with CRC or Adenomas

25% 75%

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 cancerrelated 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?

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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.

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Early Detection Saves Lives 5-Year Relative Survival Rates* for Iowa Patients Diagnosis With CRC Between 1995-2001 100% 96% 100 75

84%

100 75

50

50

25 0 Stage 0 Stage I Stage II

25 0

(Dukes’ A) (Dukes’ B)

Early Diagnosis: 60% of Patients

65%

8% Stage III Stage IV

(Dukes’ C) (Dukes’ D)

Late Diagnosis: 40% of 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.

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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 Polyps @ 50

74% after 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

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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.

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Fecal Occult Blood Testing

Winawer 2001

CRC Mortality/10 yr. (%)

0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0

Control Screened

But Only About 10-20% 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.

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Pros and Cons of FOBT Pros:

Cons:

• Evidenced based, finds most cancers, reduces mortality • Non-invasive • No bowel prep • Easy to perform, widely available • Cost-effectiveness is established

• Limited effectiveness • Requires annual testing • Patient role may be considered distasteful • Dietary restrictions used • High rate of false negatives and positives • Requires proper response 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.

NEJM 2000; 343:162)

The VA cooperative study ( 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.

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Flexible sigmoidoscopy Pros: • Office based • Easy prep • Primary care MD’s PA’s & RN’s can do • No sedation • Very cost effective • (can have same day colonoscopy) • 50-80% reduction of left-sided CRC’s

• • • •

Cons: No sedation = discomfort Limited insertion to L colon Miss rates are higher than BE/colonoscopy, especially right side • Finding polyps requires followup colonoscopy for removal • 40% of CRC in R colon

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.

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Double Contrast BE Pros: • Safe • Low cost • Cost effective • Full colon exam • High rate of reimbursement • Readily available, seldom used, no randomized trials

Cons: • Requires bowel prep • Not studied adequately • Missed 50% adenomas < 1cm, better if > 1cm • Sensitivity for pts. with (+)FOBT is 50-70% • Tolerance/expertise decr. • 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.

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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.

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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 entire colon adenomas

Can biopsy 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, 2001) examined the power of colonoscopy versus flexible sigmoidoscopy (FS) and fecal occult blood test (FOBT): How good is colonoscopy? The VA Colonoscopy Trial (

•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

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Colonoscopy Pros: • Highest accuracy • Diagnostic and therapeutic • Sedation leads to willingness to repeat • Cost effective in comparison to other tests.

Cons: • Requires bowel prep • Highest up front costs • Not always available • Highest risk of all tests (complications 1:2000) • How feasible as a national strategy?

See slide text

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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.

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Colonoscopy: Modify Indications To Increase Availability 25

(Reduce frequency) BRBPR

(FS acceptable)

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Polyp surveillance 15

(Do More)

Pain

(+)FOBT

Constipation Diarrhea

10

5

0

(Low yield)

Screen (+)FHx

Anemia

FS/BE IBD

. 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.

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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.

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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.

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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.

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Screening for CRC: What should be done? The present Benefit is proven: • • • • • •

FOBT FS FOBT + FS DCBE FS + DCBE Colonoscopy

The future Data dependent: • Virtual colonoscopy • Stool DNA testing • Genetic testing • Effective 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.

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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.

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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.

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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.

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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.

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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.

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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

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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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