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Colorectal Cancer
Bruce D. Greenwald, MD
Associate Professor of Medicine
University of Maryland
School of Medicine
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Outline
• Where is the colon and what does it do?• Why is colon cancer important?
• How many cases/year?• Who gets it?• Who dies from it?
• How does colon cancer develop?• How is colon cancer treated?• Is colon cancer preventable?
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2003 Estimated US Cancer Cases*
ONS=Other nervous system.*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2003.
Men675,300
Women658,800 210,816 Breast
79,056 Lung/bronchus
72,468 Colon & rectum
39,528 Uterine corpus
26,352 Ovary
26,352 Non-Hodgkin lymphoma
19,764 Melanoma of skin
19,764 Thyroid
13,176 Pancreas
13,176 Urinary bladder
62,238 All other sites
Prostate 222,849
Lung/bronchus 94,542
Colon/rectum 74,283
Urinary bladder 40,518
Melanoma of 27,012skin
Non-Hodgkin 27,012lymphoma
Kidney 20,259
Oral cavity 20,259
Leukemia 20,259
Pancreas 13,506
All other sites 114,801
Men675,300
Women658,800
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2003 Estimated US Cancer Deaths*
ONS=Other nervous system.*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2003.
Men285,900
Women270,600
67,650 Lung/bronchus
40,590 Breast
29,766 Colon & rectum
16,236 Pancreas
13,530 Ovary
10,824 Non-Hodgkin lymphoma
10,824 Leukemia
8,118 Uterine corpus
5,412 Brain/ONS
5,412 Multiple myeloma
62,238 All other sites
Lung/bronchus 88,629
Prostate 28,590
Colon & rectum 28,590
Pancreas 14,295
Non-Hodgkin 11,436lymphoma
Leukemia 11,436
Esophagus 11,436
Liver/intrahepatic 8,577bile duct
Urinary bladder 8,577
Kidney 8,577
All other sites 62,898
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Ethnic/Gender DifferencesIncidence per 100,000
0
5
10
15
20
25
30
35
40
Women Men
Survival (%)
6353
0
20
40
60
80
100
African-American White
Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002.
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Colon cancer rates for Baltimore City and Maryland, 1994-1998
0
10
20
30
40
50
60
70
Overall Men Women African-American
White
BaltimoreCity
Maryland
Source: Maryland Department of Health and Mental Hygience. Annual Cancer Report. September, 2001.Age-adjusted incidence per 100,000 population
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How Does Colorectal Cancer Develop?
Janne PA, Mayer RJ. N Engl J Med 2000;342:1960.
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Colon Polyp
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Colon Cancer
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How Does Colorectal Cancer Develop?
Janne PA, Mayer RJ. N Engl J Med 2000;342:1960.
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Symptoms of Colorectal Cancer
Time Course Symptoms Findings
Early None None
Occult blood in stool
Mid Rectal bleeding
Change in bowel habits
Rectal mass
Blood in stool
Late Fatigue
Anemia
Abdominal pain
Weight loss
Abdominal mass
Bowel obstruction
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Staging of Colorectal Cancer
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Frequency of Colorectal Cancer by Dukes Stage
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Survival by Dukes Stage
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Treatment of Colorectal Cancer by Stage
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Is Colorectal Cancer Preventable?
YES!
• Screening
• Chemoprevention
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Screening Techniques for Colorectal Cancer
Fecal occult blood test (FOBT) every year, or
Flexible sigmoidoscopy every 5 years,or
A fecal occult blood test every year plus flexible sigmoidoscopy every 5 years (recommended by the American Cancer Society), or
Double-contrast barium enema every 5 to 10 years, or
Colonoscopy every 10 years (recommended by the American College of Gastroenterology).
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Screening For Colon Cancer SAVES LIVES!!!
MortalityTest Reduction
Fecal occult blood testing 33%
Flexible sigmoidoscopy 66%(in portion of colon examined)
FOBT + flexible sigmoidoscopy 43%(compared to sigmoidoscopy alone)
Colonoscopy ~76-90%(after initial screening and polypectomy)
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Colorectal cancer screeningFirst assess RISK
AVERAGE RISK INDIVIDUAL• All patients age 50 years and older, the
asymptomatic general population
HIGH RISK• Personal history – polyp or cancer• Family history – polyp or cancer in first
degree relatives
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Why aren’t more people screened for colon cancer?
Reasons for refusal of fecal occult blood testing• Fear of further testing and surgery • Feeling well • Unpleasantness of stool collection procedure
But:• Strongest predictor of whether a patient will be
screened = physician encouragement
Hynam et al. J Epidemiol Comm Health 1995;49:84Mandelson et al. Am J Prevent Med 2000;19:149
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Fecal Occult Blood Testing
• Examination of stool for occult (“hidden”) blood
• Can detect one teaspoon or less of blood in a bowel movement
• Uses chemical reaction between blood and reagent
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FOBT improves survival
Years after diagnosis
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Trends in FOBT, 1997-2001
0
5
10
15
20
25
30
Total Men Women Less than HighSchool
High Schoolgraduate
Some collegeor greater
Prev
alenc
e (%) 1997
1999
2001
Source: Behavioral Risk Factor Surveillance System, 1996-1997, 1999, 2001, National Center for Chronic Disease
Prevention and Health Promotion, Centers for Disease Control and Prevention and Prevention, 1999, 2000, 2002.
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Double-contrast Barium Enema
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Double-contrast Barium Enema
• Pros• Examines entire colon• Relatively low cost
• Cons• Never studied as a screening test• Missed 50% of polyps > 1cm in one study• Detects 50-75% of cancers in those with
positive FOBT• Interval between exams unknown
Winawer et al. Gastroenterology 1997; 112:599Rex, Endoscopy 1995; 27:200Lieberman et al. N Engl J Med 2000; 343:163
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Sigmoidoscopy/Colonoscopy
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Site Distribution
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Flexible sigmoidoscopy• Pros
• May be done in office• Inexpensive, cost-effective• Reduces deaths from rectal cancer• Easier bowel preparation, usually done without
sedation• Cons
• Detects only half of polyps• Misses 40-50% of cancers located beyond the view
of the sigmoidoscope• Often limited by discomfort, poor bowel preparation
Selby et al N Engl J Med 1992; 336:653 Stewart et al Aust NZ J Surg 1999; 69:2Newcomb et al. JNCI 1992; 84:1572 Painter et al Endoscopy 1999; 3:269Rex et al. Gastrointest Endosc 1999; 99:727
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Colonoscopy
• Pros• Examines entire colon• Removal of polyps performed at time of exam• Well-tolerated with sedation• Easier bowel preparation, usually done without
sedation• Cons
• Expensive• Risk of perforation, bleeding low but not negligible• Requires high level of training to perform• Miss rate of polyps < 1 cm ~25%, > 1 cm ~5%
Rex et al. Gastroenterology 1997; 112:24-8Postic et al. Am J Gastroenterol 2002; 97:3182-5
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Colonoscopy
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Chemopreventive agents
Fiber Not effective
Aspirin May be effective
NSAIDs (ibuprofen, etc) Probably effective
Vitamin E, vitamin C, beta carotene
Not effective
Folate Effective if obtained in diet
Calcium Effective
Estrogen Effective, but has other problems
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Future techniques for colorectal cancer screening
• Stool DNA testing
• Capsule endoscopy (Givens capsule)
• CT colography (virtual colonoscopy)
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Fecal Testing for Gene Mutations
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Fecal Testing for Gene Mutations
• Pros• No sedation or preparation necessary• Home-based (sample mailed to physician)• No risk
• Cons• Current tests not very good (~50% of cancers
missed)• Cost• Frequency of exam unknown• Not therapeutic• Not covered by insurance
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Videocapsule
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Videocapsule
Lymphoma
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CT Colography
Colon Polyp
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CT Colography
Colon Polyp
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CT Colography
Colon Cancer
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CT Colography
• Pros• No sedation necessary• 20 min procedure vs. 25 min for colonoscopy• Low risk• Extracolonic lesions may be detected
• Cons• Preparation (residual fluid cannot be aspirated)• Air insufflation• Cost (? need for more frequent exams)• Radiation dose (similar to barium enema)• Not therapeutic• Not covered by insurance
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Summary
• Colorectal cancer is the third most common cancer and cause of cancer death in the U.S.
• Chemopreventive agents have modest benefit in average risk individuals
• Screening for colorectal cancer saves lives!
• Patient and physician compliance with screening is poor