Colorectal Cancer Sunil T. Joseph, M.D.

 Third leading cause of cancer-related death in U.S. (lung)  112,340 estimated new cases in 2007; 52,000 deaths 1  More than 90% cases in persons at least 50 years old 2  5-6% lifetime risk for Americans 1, 1 in 18  $6.5 billion treatment costs in 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 Epidemiology

CRC Death Rate

Epidemiology Sporadic (65-85%) Family History (10-30%) HNPCC (5%) 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: Seifeldin and Hantsch, Clin Ther 1999; 21: 1370 Year Number of admissions (thousands)

Average Annual Age-Specific US Incidence and Mortality Rates of CRC, Natl Cancer Inst, SEER Cancer Statistics Review Incidence in men Incidence in women Mortality in men Mortality in women Age group (years) Number / 100,000 population

Signs and Symptoms Blood in the stool-40% Blood in the stool-40% Change in bowel habits-43% Change in bowel habits-43% Bowel obstruction Bowel obstruction Abdominal/ Pelvic Pain-44% Abdominal/ Pelvic Pain-44%

Signs and Symptoms Weight Loss-6% Weight Loss-6% Loss of appetite Loss of appetite Fatigue-20% Fatigue-20% Anemia w/out GI symptoms-11% Anemia w/out GI symptoms-11%

Stages of Colon Cancer Stage Mortality I 90% I 90% II 80% II 80% III 50% III 50% IV 10% IV 10%

Reasons to Screen for CRC Reasons to Screen for CRC 1) Long non-mailgnant pre-stage 2) Long phase before symptoms emerge 3) Early or pre-cancer stage detectable 4) Curative tx available in pre-cancer stage 5) Sensitive screening tests available 6) Low screening risks

Cost of Colorectal Cancer Screening vs Other Medical Practices Incremental cost / life year saved (US$) Colonoscopy every 10 years: Breast cancer screening: Heart transplantation: Cervical cancer screening: 6,600 6,600 22,000 22,000160,000250,000  Colon cancer screening from age 55 years is cost-effective, but depends on compliance 2 1 Provenzale et al, Am J Gastroenterol 1999; 94: Lieberman et al, Gastroenterology 1995; 109: 1781

Adherence Rates – Cancer Screening U.S. Adherence Rates U.S. Adherence Rates Breast Cancer69% * Cervical Cancer86% * Prostate Cancer75%** Colorectal Cancer45% *63%** * Seeff Cancer 2002;95: **Sirovich JAMA 2003;289:

Factors Associated With CRC Risk factors Protective factors Strong (RR > 4.0) Advanced age Country of birth FAP / HNPCC Long-standing ulcerative colitis Moderate (RR ) High red meat diet Previous adenoma or cancer Pelvic irradiation Modest (RR ) High fat diet Smoking and alcohol consumption Obesity Cholecystectomy Moderate (RR < 0.6) High physical activity Aspirin / NSAIDs use Modest (RR ) High vegetable / fruit diet High fiber diet High folate / methionine intake High calcium intake Postmenopausal hormone therapy 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 % 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 1 st 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) Annual Fecal Occult Blood Testing (FOBT) Flexible Sigmoidoscopy Every 5 years Flexible Sigmoidoscopy Every 5 years Annual FOBT and Flex Sig Every 5years Annual FOBT and Flex Sig Every 5years Colonoscopy Every10 years Colonoscopy Every10 years Barium Enema Every 5-10 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: 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 red meats peroxidase-containing vegetables/fruits(broccoli, turnip, horseradish, cantelope, cauliflower, melon) The following medicines: Vitamin C, Aspirin, NSAIDS

Limitations to FOBT False-positive results Exogenous peroxidase activity Exogenous peroxidase activity Red meat Red meat uncooked fruits and vegetables uncooked fruits and vegetables any source of GI blood loss(gingival, epistaxis, hemorrhoids, etc) any source of GI blood loss(gingival, epistaxis, hemorrhoids, etc) medications medications ASA, NSAIDS 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

Positive Points 1) Less Invasive 2) No ride required 3) Low risk Negative Points 1) No sedation 2) Full prep 3) Only diagnostic 4) Poor sensitivity 5) Radiation exposure

Endoscopy

Flex Sig/Colonoscopy

Polypectomy

Endoscopy Flex Sig -Enemas -No sedation/No ride -1/3 of colon -Less risk Colonoscopy -Full Prep -Sedation -Entire colon -Dx and Therapeutic -Increased risk

Cumulative Incidence of Colorectal Cancer in National Polyp Study Cohort Winawer et al, New Engl J Med 1993; 329: Years of follow-up Cumulative incidence of colorectal cancer (%) No. expected from Mayo Clinic data No. expected from St. Mark’s data No. expected from SEER data No. observed

Colonoscopy in Asx Pt’s 3121 asx pt’s underwent full colonoscopy 3121 asx pt’s underwent full colonoscopy TA in 37.5%, TA >1cm or villous in 7.9%, and invasive cancer in 1.0% 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 52 % with proximal AN had no distal lesion 0.3% complication rate, no perforations 0.3% complication rate, no perforations Lieberman et al, NEJM 2000; 343:

Withdrawl Times 12 private practice gastroenterologists performed 2053 screening colonoscopies in 15 months 12 private practice gastroenterologists performed 2053 screening colonoscopies in 15 months 23.5% of patients with adenomatous polyps 23.5% of patients with adenomatous polyps Direct relation of colonoscope withdrawl time with adenoma detection; >6 minutes Direct relation of colonoscope withdrawl time with adenoma detection; >6 minutes Greenlaw et al, NEJM 2006; 355:

Flex Sig and Women 1483 Asx women recruited from 4 sites 1483 Asx women recruited from 4 sites 4.9% had AN and 15.5% had small TA 4.9% had AN and 15.5% had small TA Only 34.7% of AN detected on flex sig Only 34.7% of AN detected on flex sig 94% of prox AN with no distal findings 94% of prox AN with no distal findings Colonoscopy may be recommended test for women Colonoscopy may be recommended test for women Schoenfeld et al, NEJM 2005; 352:

African-Americans and CRC Younger mean age at diagnosis (60-66y) Younger mean age at diagnosis (60-66y) Higher incidence rates Higher incidence rates Higher mortality rates Higher mortality rates More proximal distribution of cancers and adenomas More proximal distribution of cancers and adenomas ACG now recommends that screening begin at age 45 in African-Americans ACG now recommends that screening begin at age 45 in African-Americans

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 American Gastroenterolgy Association