Colorectal Cancer Screening

Colorectal Cancer Screening “We now have clearer insight into the natural history of colorectal cancer and clinical skills with which to intervene and make a difference for many people. Colorectal cancer screening has come of age.” --Sidney J. Winawer, MD Learning Objectives  Describe the scientific rationale for colorectal cancer (CRC) screening List the characteristics of the commonly recommended CRC screening tests   Explain the differences in CRC screening guidelines among governmental and professional groups Develop an evidence-based CRC screening recommendation for your patients > 50 years  Scope of the Problem  Second leading cause of cancer-related deaths in U.S. 6% lifetime risk of developing colorectal cancer (CRC), but 3% lifetime risk of dying from the disease Mortality related with stage at diagnosis     5-year survival for early stage ca: >90% 5-year survival for metastatic ca: <10% Age-Adjusted Incidence & Mortality Incidence* Whites Mortality* Males Females African-Americans 67.6 48.0 72.1 56.9 27.3 18.8 35.1 25.7 Males Females *Rates per 100,000 adjusted to 2000 US population From SEER data, US Mortality Age-Adjusted Rates, 1969-99 and Incidence Age-Adjusted Rates, 9 Registries, 1973-1999. What are Colorectal Cancers? Heterogenous group of diseases  Sporadic (no family history)  Familial    At least one affected 1st degree relative 15%-20% of those at high risk Early age of diagnosis (< age 45) Multiple primary tumors Hereditary   Natural History   Precursor of ~90% of colorectal cancers is the adenomatous polyp Adenoma to carcinoma sequence: 7 to 10 yrs  Carcinogenesis: a process of genetic mutations and losses partially identified Rate of carcinogenesis still unknown Polyps < 1 cm -- 1% are cancerous Polyps > 2 cm -- 30% are cancerous   Polyp size correlates to cancer probability   Epidemiology  30% - 50% of population will develop adenomatous polyps over lifetime   1% - 3% of polyps become malignant Most remain asymptomatic & undetected  Prevalence of polyps increases with age  50% of men, 40% of women by age 50  > 90% of CRC diagnosed after 55 yrs Risk for Colorectal Cancer  “Average risk”   AGE: population > 50 years ~ 75% of CRC cases occur in this group Factors include personal and/or familial history of CRC or polyps, genetic syndromes (hereditary CRC), history of inflammatory bowel disease ~ 25% of CRC cases occur in this group  “High risk”   Risk for Colorectal Cancer  Dietary factors    High fat diets correlate w/ high rates of CRC Protective effects of fiber are still unproven Excessive calorie intake may enhance risk  Behavioral factors  Physical activity may reduce risk  Excessive alcohol use and smoking have been associated with increased risk Development of Colorectal Neoplasia Genetically predisposed individual Environmental Factors (Diet, smoking, inactivity) Chromosomal changes Colonic cell proliferation Adenoma Dysplasia Source: D. Lieberman, 1992. Carcinoma Early Detection of Colorectal Cancer   Detecting and removing polyps has been shown to reduce incidence of CRC Commonly used screening tests include    Digital Rectal Exam Double-Contrast Barium Enema (DCBE) Fecal Occult Blood Test (FOBT)   Flexible Sigmoidoscopy (FS) Colonoscopy Digital Rectal Examination (DRE)  Part of a comprehensive physical exam but not effective as CRC screening test   Sensitivity for CRC less than 10% Often used to obtain stool sample for FOBT with chance for increased false positive results  DRE plus one-sample FOBT performed in office most common approach to screening in U.S. Double-Contrast Barium Enema   Radiologic study—barium is used as contrast material to visualize lumen of the colon Effectiveness as screening test debated     National Polyp Study: Sensitivity of 48% for polyps > 1 cm Further evaluation required if polyps detected Less risk of perforation than endoscopic exams May be recommended with flexible sigmoidoscopy for CRC screening Fecal Occult Blood Testing (FOBT)    Detects blood from cancers or large polyps Bleeding is intermittent and increases with polyp size and stage of cancer Hemoccult II (guaiac-based) most widely used and studied FOBT   Inexpensive and easy to perform Diet and medications affect results   False positives: oral iron, aspirin, NSAIDs, anticoagualants False negatives: vitamin C Evidence of FOBT Effectiveness   5 controlled trials with 320,000 subjects Minnesota’s Colon Cancer Control Study   33% CRC mortality reduction with annual screening 18 year follow up found a lower incidence of colorectal cancer (Mandel 2000)  Trials in Denmark and United Kingdom: 15% to 18% reductions in CRC mortality with biennial screening Fecal Occult Blood Testing Issues  Processing slides with rehydration   Goal is to increase test sensitivity Tradeoff: increases sensitivity but lowers specificity and predictive value for cancer 2003 guidelines recommend against rehydration (Winawer et al. 2003)   Time delays between sampling and testing affect test results and interpretation Procedure for sampling and manner of stool collection may introduce test errors  FOBT Limitations   Limited sensitivity: 30% - 50% Specificity: highest value is 98% but decreases with rehydration of slides   Minnesota trial: 90% specificity w/ rehydration 38% of annually screened subjects received colonoscopy during 18 years of follow up Mortality benefit from “chance” colonoscopy?  More FOBT Limitations    Poor predictive value (5% -10%) False-positive rate rises with age Adherence to testing procedures a problem in controlled trials and population-based screening programs Evidence for most effective screening interval is inconclusive  Sigmoidoscopy    No controlled trials show efficacy in reducing mortality Case-control studies show a 60% to 85% reduction in mortality Advantages    Relatively accurate Quick procedure performed w/out sedation Inexpensive Sigmoidoscopy  Disadvantages   Misses 40% - 50% of CRC and polyps Risk of colon perforation is 1 to 2 per 10,000 exams Patient preparation a significant barrier to adherence   Evidence for most effective screening interval is inconclusive Colonoscopy   95% of CRC in reach of colonoscope Estimated effect of population screening: could eliminate 80% to 90% of CRC mortality in population over age 50 years Diagnostic use after positive results on FOBT or FS Recommended as initial screening test for high risk individuals   Colonoscopy  Disadvantages     Expensive Negative impact on patient’s daily life Trained endoscopists must perform Bowel perforation most serious complication--1 to 3 per 1000 procedures (Winawer et al. 1997)  No evidence from controlled trials that shows mortality reduction CRC Screening Guidelines (USPSTF)    FOBT annually and Flexible sigmoidoscopy (FS) every 5 years Screening should be individualized according to age and comorbidities Two screening options suggested   Double-contrast barium enema (DCBE) plus FS every 5 years Colonoscopy every 10 years  Other Screening Recommendations Agency for Health Care Research and Quality (AHRQ). American College of Gastroenterology, American Academy of Family Physicians, and American Cancer Society suggest one of five screening options for average risk individuals:  Annual FOBT  FS every 5 years  Annual FOBT and FS every 5 years**  DCBE every 5-10 years  Colonoscopy every 10 years **Preferred Emerging Screening Tests  Virtual Colonoscopy—thin-section, helical computerized tomography (CT) followed by off-line processing yields 3-dimensional images of the colon    Drawbacks: standard bowel prep and radiation exposure Benefits: noninvasive and no major complications Only being used in research setting; needs clinical studies of performance in average-risk patients  Altered DNA in stool—DNA recovered from stool can be analyzed for abnormalities characteristic of neoplasia   Sensitivity for CRC varies with number of abnormalities selected for analysis (sensitivity for cancer type an issue) Needs more testing in general population Cost Effectiveness of CRC Screening  Cost per year of life gained by CRC screening=$15,000 to $20,000 AHRQ Analysis: FS every 5 years and annual FOBT are most cost-effective screening strategies Patient and physician compliance with guidelines the most important variable affecting cost and cost effectiveness of screening (Lieberman 1995)   Paying for CRC Screening  CRC screening services (FOBT and FS) provided by law for all Medicare patients in January 1998 Medicare coverage of CRC screening colonoscopies for all, not just high risk individuals, began on July 1, 2001 Most third-party payers reimburse for FOBT and sigmoid exam in asymptomatic individuals   Summary of Issues  Screening for colorectal cancers with the fecal occult blood test and endoscopic exam, performed at regular intervals, reduces CRC-related mortality. Cost effectiveness of any CRC screening program ultimately relies on the willingness of clinician and patient to comply with screening recommendations.  Copyright 2003 Brown University Produced with funding from the National Cancer Institute Catherine E. Dubé, Ed.D. Principal Investigator Barbara Fuller MPH, Project Co-Director