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Colon Cancer Screening. Loyola GI Susanne Shokoohi MD. Colon Cancer. Second leading cause of cancer death in the U.S. 1 in 3 who get it will die of it 20% of colon cancer in US diagnosed when it has already metastasized Colonoscopy most used screening test (61%).
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Colon Cancer Screening Loyola GI Susanne Shokoohi MD
Colon Cancer Second leading cause of cancer death in the U.S. 1 in 3 who get it will die of it 20% of colon cancer in US diagnosed when it has already metastasized Colonoscopy most used screening test (61%)
Ideal Disease for Screening • Disease is prevalent: 140,250 new cases in 2018 • Presence of precursor lesion • Tubular adenoma: precursor of 70% of CRC • Serrated lesions: 30% • Test/treatment available to detect and treat precursor lesion or early cancer
Percent of Adults Age 50-75 up to date with Colorectal Cancer Screening 2016 • Nationwide 67% in 2016 • 1/3 of adults not screened as recommended
Why do we care? 10-15 years
Types of polyps • Adenomatous polyps • By definition, all adenomas are dysplastic. • Tubular, tubulovillous, villous adenomas. • Villous adenomas are associated with more severe degrees of dysplasia. • Low grade dysplasia vs high grade dysplasia (includes carcinoma in situ). • Serrated polyps – serrated pathyway • Hyperplastic polyps – no increased risk of cancer.
Mechanism of carcinogenesis • Adenoma-Carcinoma Hypothesis • Generally accepted that colon cancers originate within previously benign adenomas and serrated polyps. • Progression from adenoma carcinoma results from accumulation of mutations. • Tumor initiation: Formation of the adenoma. • Tumor progression: Progression of the adenoma to carcinoma.
Risk Factors Nonmodifiable risk: Male gender, age > 50, AA race, genetics/family history
Gender and CRC Screening • Women have a lower age-adjusted risk of CRC and advanced adenoma • Lag time of 7-8 years • CRC risk • 50 year old Man = • 58 year old Woman • Hormonal delay of CRC from menopause Levin et al. Gastroenterology 2008; 134: 1570-1595
Race and CRC Screening • African Americans have higher CRC incidence and mortality • Access to care reduced • Failure of physicians to recommend screening • Biologic/genetic predisposition • Many groups (such as ACG) recommend screening for African Americans starting at age 45 Levin et al. Gastroenterology 2008; 134: 1570-1595
Family History • Possible hereditary syndrome if • CRC <50 • multiple family members with CRC • Familial Polyposis • Lynch Tumors • Uterine, gastric, ovarian, small bowel, pancreas Bresalier and Robert S. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 2016. 2248-2296
Familial Adenomatous Polyposis (FAP) • Autosomal Dominant • Polyps appear at age 16 • Average age of colon cancer is 39 • Increased risk for small intestine and gastric cancers, and other types of cancer • Treatment: surveillance, colectomy
Lynch Syndrome= HNPCC • Autosomal dominant • Earlier age of CRC onset ~ 45 years • Higher rates of synchronous CRC • Risk of endometrial, ovarian cancers, bladder, stomach, small bowel, • Treatment- colectomy, hysterectomy
Prognosis www.Cancer.org
Screening Justification • Major health problem • Effective therapy exists • Sensitive/specific screening test • Cost effective Bresalier and Robert S. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 2016. 2248-2296
Who to Screen • Average risk (no family history, no symptoms): age 50 • African Americans: age 45 • Family history: • Documented first degree relative with colon cancer or advanced adenoma age < 60 years OR • Two first degree relatives with these findings at any age • Colonoscopy q 5 years, beginning 10 years prior to diagnosis or age 40, whichever is earlier • What to do when the patient reaches 60
CRC Screening Based on Family History Levin et al. Gastroenterology 2008; 134: 1570-1595
Colon Cancer: Not decreasing for everyone • Incidence of CRC in adults younger than 50 is increasing • More than a tenth (11% of colon and 18% of rectal cancer) occur at age < 50 • More likely to present with advanced disease Kristin Freiborg, age 22. New York Times, February 28, 2017
Age < 50 Age > 50
SEER Study: 1975-2010 • By 2030, incidence rate will increase by 90% in 20-34 year old age group • Compared with adults born around 1950, those born in 1990 have double the risk of colon cancer and quadruple the risk of rectal cancer • Young patients more commonly have symptomatic, later stage, mucinous, and poorly differentiated tumors • Should screening begin at 40? So far no change in recommendations
Screening Tests Structural tests Stool based tests • Barium Enema • CT Colonography • Sigmoidoscopy • Colonoscopy • Fecal Occult Blood Testing (FOBT) • Fecal Immunochemical Testing (FIT) • Fecal DNA testing Levin et al. Gastroenterology 2008; 134: 1570-1595 Bresalier and Robert S. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 2016. 2248-2296
FOBT • Detection of occult blood in the stool through a chemical reaction (looks at peroxidase activity). • One stool sample not adequate (3 samples from 3 consecutive BMs) • Convenient, easy to use, cheap • Interval: annual • Decreased mortality • 15-33% • Downsides: Can be falsely positive due to diet: red meat, vitamin C (> 250 mg daily), NSAIDs. • Positive FOBT should not trigger consult for GI bleed! Levin et al. Gastroenterology 2008; 134: 1570-1595 Bresalier and Robert S. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 2016. 2248-2296
FOBT Red meat Broccoli Turnips Cauliflower Radishes Cantaloupe Iron supplements Aspirin NSAIDs Less sensitive for proximal colon Only 1 specimen Specimen hydration Bresalier and Robert S. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 2016. 2248-2296
FIT(Fecal Immunochemical Testing) • Uses antibodies directed against human hemoglobin • One stool sample • Annual testing • Hemoglobin in upper GI tract is broken down by time reaches colon thus not detected by FIT • No diet or drug restrictions • Preferred form of FOBT in screening guidelines Bresalier and Robert S. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 2016. 2248-2296
FIT Test • One sample. Paper that goes across rim of toilet, poop on that, poke poop a few times with applicator and put in collection tube, mail it in. • $22 • Recommended annually
Cologuard • Combination of FIT test plus DNA analysis of cells shed from polyps and tumors • Collection kit with two sample containers (one for FIT, one for DNA, only need one poop) • No dietary modification • Store at room temperature, mail within 72 hours • ~$600
Pivotal study • 9,989 average risk patients who received FIT and Cologuard, followed by colonoscopy1 • NNT (number need to screen to detect one cancer): • Colonoscopy 154 • Cologuard 166 • FIT 208 1. Imperiale T et al. Multi-target stool DNA testing for colorectal cancer screening. NEJM 2014;370:1287-1297.
Positive Cologuard: What Happens With Colonoscopy • Study of patients with positive cologuard • Compared colonoscopy findings when the endoscopist knew cologuard was positive versus not knowing • More adenomas/SSAs found in the unblinded group (70% vs 53%, p =0.013) and advanced neoplasms (28% vs 21%, p=NS) Johnson, D et al. GIE 2017;85:657-665.
Capsule Colonoscopy • Approved by FDA for imaging the proximal colon in patients with prevous incomplete colonoscopy • Patients who need colorectal imaging but are not candidates for colonoscopy or sedation
Capsule Colonoscopy • Not approved for screening average risk people • Extensive bowel prep required • 88% sensitive for adenoma > 6 mm • Ineffective for serrated lesions • 9% of pts in rigorous study had inadequate bowel prep
Colonoscopy • Gold-standard • Reduces cancer and mortality • Direct mucosal inspection of the entire colon Levin et al. Gastroenterology 2008; 134: 1570-1595 Bresalier and Robert S. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 2016. 2248-2296
Risks of Colonscopy • Sedation • Bleeding • Range from 0.2-10% for polypectomy • Can be delayed up to 2 weeks • Perforation • Approximately 1 in 2,000-10,000 Colonoscopy: Principles and Practice. 2nd edition Edited by Jerome D. Waye, Douglas K. Rex and Christopher B. Williams. 2009 Blackwell Publishing Ltd. Levin et al. Gastroenterology 2008; 134: 1570-1595
Colonoscopy Limitations • Requires a bowel preparation • Usually perceived as most unpleasant part • Usually done with sedation • Patients need transportation • Miss a day of work • Requires a chaperone • Operator dependent • Missed lesions • Small but present risks Levin et al. Gastroenterology 2008; 134: 1570-1595 Bresalier and Robert S. Sleisenger and Fordtran's Gastrointestinal and Liver Disease 2016. 2248-2296
Colonoscopy Intervals Levin et al. Gastroenterology 2008; 134: 1570-1595
Surveillance Guidelines Assumption • Baseline exam was of high quality; good prep and everything removed completely • Monitor adenoma detection rates and withdrawal times • ADR benchmark is currently > 25% overall, >30% for males and > 20% for females • Higher ADR = more protective • Kaminiski M et al. NEJM 2010;362:1795-1803 • Baxter N et al. Gastroenterol 2011;140:65-72