1. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View menu, select the Slide Show option * To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide

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3. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. in the clinic Screening for Colorectal Cancer

4. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. Can patients reduce their risk for CRC by modifying their health behaviors or using certain drugs?  Health behaviors that may reduce risk  Moderate intake red meat and saturated & unsaturated fat  Regular physical activity  Maintenance of normal body weight  Avoidance of alcohol and tobacco  Consumption of 5–7 daily servings fresh fruits, vegetables  Diet rich in calcium, folate, selenium, vitamins A, D, E  Postmenopausal estrogen, aspirin and other NSAIDs  Balance of benefits vs. harms doesn’t favor use of estrogen or NSAIDS for primary prevention

5. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. Does screening prevent CRC?  Prevents disease-associated morbidity and mortality  Also reduces cancer incidence  Precancerous adenomatous polyps identified and removed

6. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. CLINICAL BOTTOM LINE: Prevention…  Health behaviors can decrease CRC risk  Improving dietary intake  Increasing physical exercise  Taking aspirin regularly  Screening plays a major role in primary prevention  Powerful way to reduce CRC incidence and mortality  Proven public health benefit

7. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. What are the precursors of CRC?  Adenomatous polyps  Focal point of screening: identifying and removing polyps  Terminology for adenomas: tubular, tubulovillous, villous, mixed, serrated  Advanced adenomas  Measure ≥1 cm  Foci of high-grade dysplasia  Tubulovillous or villous component  Increased long-term risk for cancer  Merit more frequent surveillance  Prevalence at screening colonoscopy: 5%–10%

8. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1.  Serrated lesions  Originally not believed to be associated with cancer  Subset now known to be colon cancer precursors: “Sessile serrated adenoma” and “sessile serrated polyp”  Number + type of adenoma dictate surveillance interval  Occurrence of CRC after screening = interval cancer  Due, in part, to missed lesions (suboptimal colonoscopy)  Accounts for 5%–8% of all cases  Adenoma detection rate (ADR): % cases in which adenomas detected  Guidelines recommend overall ADR ≈25% for endoscopist  Lower ADRs: increased risk for (preventable) CRC

9. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1.  Fecal occult blood testing (FOBT)  Positive results require follow-up colonoscopy  Many false-positives; repeated testing needed What methods are effective in CRC screening?  Fecal immunochemical testing (FIT)  Measures intact human globin protein (vs. heme)  Requires 1 stool specimen vs. 3 for FOBT; less stool handling, more specific for lower GI bleeding  Detects more advanced adenomas than FOBT  Lower cutoff for positive results increases sensitivity for neoplasia detection  Flexible sigmoidoscopy  Greater benefit in the distal vs proximal colon

10. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1.  Colonoscopy  Visual exam of entire colon, combines Dx and treatment  Increased detection of adenomas and carcinomas compared with FOBT, FIT, or flexible sigmoidoscopy  Disadvantages: colonic prep, sedation, lost work time and need for transport, cost, invasive nature; complication risk  CT Colonography  Noninvasive and can examine entire colon  Minimal complication rate  Effective visualizing lesions that protrude into lumen  Colonic preparation required  Colonoscopy required to remove detected polyps

11. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. What are the emerging CRC screening techniques?  Fecal DNA testing  Colonic mucosal cells continually shed into fecal stream  So are cells shed by colonic neoplasms  Test allows identification of cells with specific genetic or epigenetic changes  Noninvasive detection of CRC, perhaps large adenomas  May detect serrated polyps  Fecal DNA + FIT: 92% sensitivity, 87% specificity for CRC  Cost: primary obstacle that inhibits broader adoption

12. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. How should clinicians and patients select from among different screening methods?  No clear evidence that one outperforms another  Each test has advantages and disadvantages  Colonoscopy favored in U.S., but not necessarily best test  Compliance better with simpler, less demanding fecal test?  When choosing screening option, weigh:  Costs  Availability  Convenience  Patient preference

13. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. Is CRC screening cost-effective?  CRC screening is considered cost effective  Reduces cancer incidence  Leads to fewer patients requiring treatment  Cost for treating established CRC has accelerated  Newer targeted therapies are expensive  Ensuring the cost-effectiveness of screening

14. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. What are the risks for patients?  Most adenomas detected and removed via screening are unlikely to progress to CRC  The screening process operates on “overkill”  We can’t tell which adenomas will progress, so all removed  Approach substantially reduces CRC mortality + incidence

15. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. At what age should patients begin screening?  Average-risk persons:  Initiate screening at age 50

16. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. How frequently should patients repeat screening?  If no adenomas are found…  FOBT or FIT: repeat annually  Flexible sigmoidoscopy: repeat every 5 years  Colonoscopy: repeat every 10 years  If adenomas detected: next recommended interval test…  Hyperplastic polyp: 10 years  1-2 Nonadvanced adenomas: 5–10 years  ≥3 Nonadvanced adenomas: 3 years  Advanced adenoma (≥1cm, with villous components, or with high-grade dysplasia): 3 years  Type, number, size of polyps guides follow-up frequency

17. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. At what age should average-risk patients stop screening?  Depends on life expectancy and anticipated benefit  Limited life expectancy reduces potential benefit  Harms of screening may increase for elderly patients  OK to stop at age 75 years or if life expectancy <10 yrs

18. © Copyright Annals of Internal Medicine, 2014 Ann Int Med. 160 (5): ITC5-1. CLINICAL BOTTOM LINE: Screening…  For general population: Screening is a key component of preventive health  Cost-effective  Should begin at 50 years of age  Continue at regular intervals well into later adulthood  Unless there is a compelling contraindication  Accomplished through a number of accepted methods  Fecal testing, flexible sigmoidoscopy, colonoscopy