1. Colorectal Cancer
Bruce D. Greenwald, MD
Associate Professor of Medicine
University of Maryland
School of Medicine

2. 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?

4. 2003 Estimated US Cancer Cases*
Men
Men Women
Prostate 222,849 210,816 Breast
675,300
675,300 658,800
Lung/bronchus 94,542 79,056 Lung/bronchus
Colon/rectum 74,283 72,468 Colon & rectum
Urinary bladder 40,518 39,528 Uterine corpus
Melanoma of 27,012 26,352 Ovary
skin
26,352 Non-Hodgkin
Non-Hodgkin 27,012 lymphoma
lymphoma
19,764 Melanoma of
Kidney 20,259 skin
Oral cavity 20,259 19,764 Thyroid
Leukemia 20,259 13,176 Pancreas
Pancreas 13,506 13,176 Urinary bladder
All other sites 114,801 62,238 All other sites
ONS=Other nervous system.
*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2003.

5. 2003 Estimated US Cancer Deaths*
Men Women
Lung/bronchus 88,629 67,650 Lung/bronchus
285,900 270,600
Prostate 28,590 40,590 Breast
Colon & rectum 28,590 29,766 Colon & rectum
Pancreas 14,295 16,236 Pancreas
Non-Hodgkin 11,436 13,530 Ovary
lymphoma
10,824 Non-Hodgkin
Leukemia 11,436 lymphoma
Esophagus 11,436 10,824 Leukemia
Liver/intrahepatic 8,577 8,118 Uterine corpus
bile duct
5,412 Brain/ONS
Urinary bladder 8,577
5,412 Multiple myeloma
Kidney 8,577
62,238 All other sites
All other sites 62,898
ONS=Other nervous system.
*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2003.

6. Ethnic/Gender Differences
Incidence per 100,000 Survival (%)
40 100
35
80
30
63
53
25 60
20
15 40
10
20
5
0 0
Women Men
African-American White
Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control
and
Population Sciences, National Cancer Institute, 2002.

7. Colon cancer rates for Baltimore City
and Maryland, 1994-1998
70
60 Baltimore
City
50 Maryland
40
30
20
10
0
Overall Men Women African- White
American
Source: Maryland Department of Health and Mental Hygience. Annual Cancer Report. September, 2001.
Age-adjusted incidence per 100,000 population

8. How Does Colorectal Cancer Develop?
Janne PA, Mayer RJ. N Engl J Med 2000;342:1960.

9. Colon Polyp

10. Colon Cancer

11. How Does Colorectal Cancer Develop?
Janne PA, Mayer RJ. N Engl J Med 2000;342:1960.

12. Symptoms of Colorectal Cancer
Time Course Symptoms Findings
Early None None
Occult blood in stool
Mid Rectal bleeding Rectal mass
Change in bowel Blood in stool
habits
Late Fatigue Weight loss
Anemia Abdominal mass
Abdominal pain Bowel obstruction

13. Staging of Colorectal Cancer

14. Frequency of Colorectal Cancer by
Dukes Stage

15. Survival by Dukes Stage

16. Treatment of Colorectal Cancer
by Stage

17. Is Colorectal Cancer Preventable?
YES!
• Screening
• Chemoprevention

18. 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).

19. Screening For Colon Cancer
SAVES LIVES!!!
Mortality
Test 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)

20. Colorectal cancer screening
First 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

21. 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;49:84
Mandelson et al. Am J Prevent Med 2000;19:149

22. 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

23. FOBT improves survival
Years after diagnosis

24. Trends in FOBT, 1997-2001
30
25
20
1997
Prevalence (%)
15
1999
10
2001
5
0
Total Men Women Less than High High School Some college
School graduate or greater
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.

25. Double-contrast Barium Enema

26. 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; 112:599
Rex, Endoscopy 1995; 27:200
Lieberman et al. N Engl J Med 2000; 343:163

27. Sigmoidoscopy/Colonoscopy

28. Site Distribution

29. 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; 69:2
Newcomb et al. JNCI 1992; 84:1572 Painter et al Endoscopy 1999; 3:269
Rex et al. Gastrointest Endosc 1999; 99:727

30. 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; 112:24-8
Postic et al. Am J Gastroenterol 2002; 97:3182-5

31. Colonoscopy

32. Chemopreventive agents
Fiber Not effective
Aspirin May be effective
NSAIDs (ibuprofen, etc) Probably effective
Vitamin E, vitamin C, beta Not effective
carotene
Folate Effective if obtained in
diet
Calcium Effective
Estrogen Effective, but has other
problems

33. Future techniques for colorectal
cancer screening
• Stool DNA testing
• Capsule endoscopy (Givens capsule)
• CT colography (virtual colonoscopy)

34. Fecal Testing for Gene Mutations

35. 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

36. Videocapsule

37. Videocapsule
Lymphoma

38. CT Colography
Colon Polyp

39. CT Colography
Colon Polyp

40. CT Colography
Colon Cancer

41. 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

42. 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