8/13/2019 Greenwald Pp t

1/42

Colorectal Cancer

Bruce D. Greenwald, MD

Associate Professor of Medicine

University of Maryland

School of Medicine

8/13/2019 Greenwald Pp t

2/42

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?

8/13/2019 Greenwald Pp t

3/42

8/13/2019 Greenwald Pp t

4/42

8/13/2019 Greenwald Pp t

5/42

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-Hodgkinlymphoma

10,824 Leukemia

8,118 Uterine corpus

5,412 Brain/ONS

5,412 Multiple myeloma

62,238 All other sites

Lung/bronchus 88,629Prostate 28,590

Colon & rectum 28,590

Pancreas 14,295

Non-Hodgkin 11,436lymphoma

Leukemia 11,436

Esophagus 11,436

Liver/intrahepatic 8,577

bile ductUrinary bladder 8,577

Kidney 8,577

All other sites 62,898

8/13/2019 Greenwald Pp t

6/42

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 andPopulation Sciences, National Cancer Institute, 2002.

8/13/2019 Greenwald Pp t

7/42

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

8/13/2019 Greenwald Pp t

8/42

How Does Colorectal Cancer Develop?

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

8/13/2019 Greenwald Pp t

9/42

Colon Polyp

8/13/2019 Greenwald Pp t

10/42

8/13/2019 Greenwald Pp t

11/42

How Does Colorectal Cancer Develop?

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

8/13/2019 Greenwald Pp t

12/42

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

8/13/2019 Greenwald Pp t

13/42

Staging of Colorectal Cancer

8/13/2019 Greenwald Pp t

14/42

8/13/2019 Greenwald Pp t

15/42

Survival by Dukes Stage

8/13/2019 Greenwald Pp t

16/42

Treatment of Colorectal Cancer

by Stage

8/13/2019 Greenwald Pp t

17/42

Is Colorectal Cancer Preventable?

YES!

Screening

Chemoprevention

8/13/2019 Greenwald Pp t

18/42

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 flexiblesigmoidoscopy every 5 years (recommended bythe Am erican Cancer Society),or

Double-contrast barium enema every 5 to 10years, or

Colonoscopy every 10 years (recommended bythe American Co l lege of Gastroenterolog y).

8/13/2019 Greenwald Pp t

19/42

8/13/2019 Greenwald Pp t

20/42

Colorectal cancer screening

First assess RISK

AVERAGE RISK INDIVIDUAL

All patients age 50 years and older, the

asymptomatic general population

HIGH RISK

Personal historypolyp or cancer

Family historypolyp or cancer in firstdegree relatives

8/13/2019 Greenwald Pp t

21/42

Why arent 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

8/13/2019 Greenwald Pp t

22/42

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

8/13/2019 Greenwald Pp t

23/42

FOBT improves survival

Years after diagnosis

8/13/2019 Greenwald Pp t

24/42

Trends in FOBT, 1997-2001

0

5

1015

20

25

30

Total Men Women Less than High

School

High School

graduate

Some college

or greater

Prevale

nce(%)

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.

8/13/2019 Greenwald Pp t

25/42

8/13/2019 Greenwald Pp t

26/42

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

8/13/2019 Greenwald Pp t

27/42

Sigmoidoscopy/Colonoscopy

8/13/2019 Greenwald Pp t

28/42

Site Distribution

8/13/2019 Greenwald Pp t

29/42

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

8/13/2019 Greenwald Pp t

30/42

Colonoscopy

Pros Examines entire colon

Removal of polyps performed at time of exam

Well-tolerated with sedation

Easier bowel preparation, usually done withoutsedation

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

8/13/2019 Greenwald Pp t

31/42

Colonoscopy

8/13/2019 Greenwald Pp t

32/42

Chemopreventive agents

Fiber Not effective

Aspirin May be effective

NSAIDs (ibuprofen, etc) Probably effective

Vitamin E, vitamin C, betacarotene

Not effective

Folate Effective if obtained in

diet

Calcium Effective

Estrogen Effective, but has other

problems

8/13/2019 Greenwald Pp t

33/42

8/13/2019 Greenwald Pp t

34/42

Fecal Testing for Gene Mutations

8/13/2019 Greenwald Pp t

35/42

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

8/13/2019 Greenwald Pp t

36/42

Videocapsule

8/13/2019 Greenwald Pp t

37/42

Videocapsule

Lymphoma

8/13/2019 Greenwald Pp t

38/42

CT Colography

Colon Polyp

8/13/2019 Greenwald Pp t

39/42

8/13/2019 Greenwald Pp t

40/42

CT Colography

Colon Cancer

8/13/2019 Greenwald Pp t

41/42

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

8/13/2019 Greenwald Pp t

42/42

Summary

Colorectal cancer is the third most commoncancer 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 withscreening is poor