Transcript Slide 1

Colorectal Cancer
Sunil T. Joseph, M.D.
Epidemiology
 Third leading cause of cancer-related death
in U.S. (lung)
 112,340 estimated new cases in 2007;
52,000 deaths1
 More than 90% cases in persons at least 50
years old2
 5-6% lifetime risk for Americans1 , 1 in 18
 $6.5 billion treatment costs in 20023
Epidemiology
 Annual incidence in U.S.:
- M: 62 per 100,000
- F: 47 per 100,000
 Increasing right sided colon cancers
 US has lowest mortality rate despite highest
incidence
CRC Death Rate
Epidemiology
Family History (10-30%)
HNPCC (5%)
Sporadic (65-85%)
FAP (1%)
Rare syndromes
(<0.1%)
Adenomas - Precursor
lesions
Polyps
Tubular Adenomas
-2/3 of polyps; 25% prevalence in> 50
Hyperplastic Polyps
Villous Adenomas
Serated Adenomas
Projected Annual Hospital Admissions for
Colon Cancer in the US: 1990-2050
Number of admissions (thousands)
500
400
300
200
Projected admissions,
50 yrs and over
100
0
1990
2000
2010
2020
2030
2040
2050
Year
Seifeldin and Hantsch, Clin Ther 1999; 21: 1370
Average Annual Age-Specific US Incidence and
Mortality Rates of CRC, 1992-1996
Number / 100,000 population
600
Incidence in men
500
400
300
Incidence in women
Mortality in men
Mortality in women
200
100
0
30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84
85+
Age group (years)
Natl Cancer Inst, SEER Cancer Statistics Review 1973-1996
Signs and Symptoms
• Blood in the stool-40%
• Change in bowel habits-43%
• Bowel obstruction
• Abdominal/ Pelvic Pain-44%
Signs and Symptoms
• Weight Loss-6%
• Loss of appetite
• Fatigue-20%
• Anemia w/out GI symptoms-11%
Stages of Colon Cancer
Stage
I
II
III
IV
Mortality
90%
80%
50%
10%
Reasons to Screen for CRC
1)
2)
3)
4)
5)
6)
Long non-mailgnant pre-stage
Long phase before symptoms emerge
Early or pre-cancer stage detectable
Curative tx available in pre-cancer stage
Sensitive screening tests available
Low screening risks
Cost of Colorectal Cancer Screening
vs Other Medical Practices
Incremental cost /
life year saved (US$)
Colonoscopy every 10 years:
6,600
Breast cancer screening:
22,000
Heart transplantation:
160,000
Cervical cancer screening:
250,000
 Colon cancer screening from age 55 years is cost-effective,
but depends on compliance2
1Provenzale
2Lieberman
et al, Am J Gastroenterol 1999; 94: 268
et al, Gastroenterology 1995; 109: 1781
Adherence Rates –
Cancer Screening
Breast Cancer
Cervical Cancer
Prostate Cancer
Colorectal Cancer
U.S. Adherence Rates
69% *
86% *
75%**
45% *
63%**
* Seeff Cancer 2002;95:2211-22
**Sirovich JAMA 2003;289:1414-20
Factors Associated With CRC
Risk factors
Strong (RR > 4.0)
Advanced age
Country of birth
FAP / HNPCC
Long-standing ulcerative colitis
Moderate (RR 2.1 - 4.0)
High red meat diet
Previous adenoma or cancer
Pelvic irradiation
Protective factors
Moderate (RR < 0.6)
High physical activity
Aspirin / NSAIDs use
Modest (RR 0.9 - 0.6)
High vegetable / fruit diet
High fiber diet
High folate / methionine intake
High calcium intake
Postmenopausal hormone therapy
Modest (RR 1.1 - 2.0)
High fat diet
Smoking and alcohol consumption
Obesity
Cholecystectomy
Sandler, Gastroenterol Clin N Am 1996; 27: 717
Familial Adenomatous Polyposis
-Autosomal dominant inheritance
-100’s to 1000’s of polyps
-Associated with gastric cancer
-Polyps develop at age 20
-100% chance of developing colon
cancer
Lynch Syndrome (HNPCC)
-Autosomal Dominant Inheritance
-Proximal colon cancer
-70% lifetime risk of developing cancer
-Amsterdam criteria
-Association with stomach, kidney, pelvic,
and small bowel cancer
Family History of CRC
-Single 1st degree relative increases
risk 1.7 X
-Multiple relatives increases risk
-Age less than 60
-Family history of tubular adenomas
Guidelines
• Annual Fecal Occult Blood Testing (FOBT)
• Flexible Sigmoidoscopy Every 5 years
• Annual FOBT and Flex Sig Every 5years
• Colonoscopy Every10 years
• Barium Enema Every 5-10 years
Fecal Occult Blood Testing
Proper Performance of slide Guaiac Test
for Fecal Occult Blood
For 3 days before and during testing, patients should avoid:
• red meats
• peroxidase-containing vegetables/fruits(broccoli,
turnip, horseradish, cantelope, cauliflower, melon)
• The following medicines:
Vitamin C, Aspirin, NSAIDS
Two samples of each of 3 spontaneously passed stool tested
Slides should be developed within 4-6 days
Slides should not be rehydrated before developing
Limitations to FOBT
False-positive results

Exogenous peroxidase
activity




Red meat
uncooked fruits and vegetables
any source of GI blood
loss(gingival, epistaxis,
hemorrhoids, etc)
medications

ASA, NSAIDS
False-Negative Results





Storage of slides
Ascorbic acid(Vitamin C)
Improper sampling/
developing
Lesion not detected at the time
of stool collection
Degradation of hemoglobin by
colonic bacteria
Barium Enema
Barium Enema
Positive Points
Negative Points
1)
Less Invasive
1)
No sedation
2)
No ride required
2)
Full prep
Low risk
3)
Only diagnostic
4)
Poor sensitivity
5)
Radiation
3)
exposure
Endoscopy
Flex Sig/Colonoscopy
Polypectomy
Endoscopy
Flex Sig
Colonoscopy
-Enemas
-Full Prep
-No sedation/No ride
-Sedation
-1/3 of colon
-Entire colon
-Less risk
-Dx and Therapeutic
-Increased risk
Cumulative Incidence of Colorectal Cancer in
National Polyp Study Cohort
Cumulative incidence of colorectal cancer (%)
5
No. expected
from Mayo Clinic data
4
No. expected
from St. Mark’s data
3
2
No. expected
from SEER data
1
No. observed
0
0
1
2
3
4
5
6
7
8
Years of follow-up
Winawer et al, New Engl J Med 1993; 329: 1977
Colonoscopy in Asx Pt’s
• 3121 asx pt’s underwent full colonoscopy
• TA in 37.5%, TA >1cm or villous in 7.9%,
and invasive cancer in 1.0%
• 52 % with proximal AN had no distal lesion
• 0.3% complication rate, no perforations
Lieberman et al, NEJM 2000; 343: 162-168.
Withdrawl Times



12 private practice gastroenterologists
performed 2053 screening colonoscopies in 15
months
23.5% of patients with adenomatous polyps
Direct relation of colonoscope withdrawl time
with adenoma detection; >6 minutes
Greenlaw et al, NEJM 2006; 355: 2533-41.
Flex Sig and Women
• 1483 Asx women recruited from 4 sites
• 4.9% had AN and 15.5% had small TA
• Only 34.7% of AN detected on flex sig
• 94% of prox AN with no distal findings
• Colonoscopy may be recommended test
for women
Schoenfeld et al, NEJM 2005; 352: 2061-8.
African-Americans and CRC





Younger mean age at diagnosis (60-66y)
Higher incidence rates
Higher mortality rates
More proximal distribution of cancers
and adenomas
ACG now recommends that screening
begin at age 45 in African-Americans
CT Colonography
CT Colonography
1)
Preparation: Go-Lytely vs. Fleets
2)
Rectal tube: CO2 vs. Room air
3)
Prone and Supine-Glucagon
4)
Breath hold: 3-4X30 second/1X20 second
5)
2D/3D reconfiguration
Advantages
1)
Non-invasive
2)
No sedation
3)
Short exam time-20 minutes
4)
Patient preference
5)
Extra-colonic findings
6)
Localization and both sides of folds
Disadvantages
1)
Prepped colon
2)
Purely diagnostic
3)
Radiation exposure
4)
Significant learning curve
5)
False positive: bowel distension/stool
6)
Flat lesions
What Can I Do to
Prevent Colon
Cancer?
Prevention
1) Diet high in fruits and
vegetables
2) Minimize red meat intake
3) Increased fiber intake
4) Folic acid/Vitamin D/Calcium
5) Increased physical activity
Prevention
6) Aspirin/NSAID’s
7) Statins
8) Hormone replacement therapy
Websites
American Cancer Society
Colon Cancer Alliance
www.cancer.org
www.ccalliance.org
American Gastroenterolgy www.gastro.org
Association