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*

Prostate Lung/bronchus 222,849 94,542 Men Men 675,300 675,300 Women 658,800 210,816 Breast 79,056 Lung/bronchus

Colon/rectum
Melanoma of skin

74,283
27,012

72,468 Colon & rectum

39,528 Uterine corpus 26,352 Ovary 26,352 Non-Hodgkin lymphoma 19,764 Melanoma of skin 19,764 Thyroid

Urinary bladder 40,518

Non-Hodgkin lymphoma
Kidney Oral cavity

27,012
20,259 20,259

Leukemia
Pancreas All other sites

20,259
13,506 114,801

13,176 Pancreas
13,176 Urinary bladder 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.

2003 Estimated US Cancer Deaths*

Lung/bronchus Prostate Pancreas Non-Hodgkin lymphoma 88,629 28,590 14,295 11,436 Men 285,900 Women 270,600 67,650 Lung/bronchus 40,590 Breast

Colon & rectum 28,590

29,766 Colon & rectum

16,236 Pancreas 13,530 Ovary 10,824 Non-Hodgkin lymphoma 10,824 Leukemia 8,118 5,412 5,412 Uterine corpus Brain/ONS Multiple myeloma

Leukemia
Esophagus

11,436
11,436

Liver/intrahepatic 8,577 bile duct

Urinary bladder
Kidney All other sites

8,577
8,577 62,898

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.

Ethnic/Gender Differences
Incidence per 100,000
40 35
80 100

Survival (%)

30 25 20 15 10
20 40

53
60

63

5 0 Women Men
African-American White
0

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

70 60 50 40 30 20 10 0
Overall Men Women AfricanAmerican White

Baltimore City 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 Early Symptoms None Findings None Occult blood in stool

Mid

Rectal bleeding Change in bowel habits

Fatigue Anemia Abdominal pain

Rectal mass Blood in stool

Weight loss Abdominal mass Bowel obstruction

Late

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!!!

Test
Fecal occult blood testing Flexible sigmoidoscopy
(in portion of colon examined)

Mortality Reduction 33% 66% 43% ~76-90%

FOBT + flexible sigmoidoscopy

(compared to sigmoidoscopy alone)

Colonoscopy
(after initial screening and polypectomy)

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

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

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

30
Prevalence (%)

25 20 15 10 5 0
Total Men Women Less than High High School Some college School graduate or greater

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; 112:599 Rex, Endoscopy 1995; 27:200 Lieberman 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
Stewart et al Aust NZ J Surg 1999; 69:2 Painter et al Endoscopy 1999; 3:269

Selby et al N Engl J Med 1992; 336:653 Newcomb et al. JNCI 1992; 84:1572 Rex 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; 112:24-8 Postic et al. Am J Gastroenterol 2002; 97:3182-5

Colonoscopy

Chemopreventive agents
Fiber Aspirin NSAIDs (ibuprofen, etc) Not effective May be effective Probably effective

Vitamin E, vitamin C, beta Not effective carotene Folate Calcium Estrogen Effective if obtained in diet Effective 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