PowerPoint Presentation

Colorectal Cancer

Bruce D. Greenwald, MD

Associate Professor of Medicine

University of Maryland

School of Medicine

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?

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

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

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.

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

How Does Colorectal Cancer Develop?

Janne PA, Mayer RJ. N Engl J Med 2000;342:1960.

Colon Polyp

Colon Cancer

How Does Colorectal Cancer Develop?

Janne PA, Mayer RJ. N Engl J Med 2000;342:1960.

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

Staging of Colorectal Cancer

Frequency of Colorectal Cancer by Dukes Stage

Survival by Dukes Stage

Treatment of Colorectal Cancer by Stage

Is Colorectal Cancer Preventable?

YES!

• Screening

• Chemoprevention

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).

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)

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

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

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

FOBT improves survival

Years after diagnosis

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.

Double-contrast Barium Enema

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

Sigmoidoscopy/Colonoscopy

Site Distribution

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

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

Colonoscopy

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

Future techniques for colorectal cancer screening

• Stool DNA testing

• Capsule endoscopy (Givens capsule)

• CT colography (virtual colonoscopy)

Fecal Testing for Gene Mutations

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

Videocapsule

Videocapsule

Lymphoma

CT Colography

Colon Polyp

CT Colography

Colon Polyp

CT Colography

Colon Cancer

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

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