1. Colorectal Cancer Awareness in TN: Risk Factors, Screening, Outreach Keith D. Gray, M.D. Assistant Professor of Surgery Division of Surgical Oncology The University of Tennessee Medical Center

2. CRC Facts 2008, 150K new cases and 50K deaths Lifetime risk of developing colon cancer is 1 in 19 2 nd leading cause of cancer death among men and women combined Death rate has been decreasing over last 20 years, due to earlier screening and better imaging and treatment

3. Uncontrollable Risk Factors for Developing Colorectal Cancer Age – 50 or olderAge – 50 or older Family history of cancer of the colon or rectumFamily history of cancer of the colon or rectum Personal history of cancer of the colon, rectum, ovary, endometrium or breastPersonal history of cancer of the colon, rectum, ovary, endometrium or breast History of polyps of the colonHistory of polyps of the colon Inflammatory bowel disease – ulcerative colitis or Crohns diseaseInflammatory bowel disease – ulcerative colitis or Crohns disease Hereditary conditionsHereditary conditions

4. Controllable Risk Factors for Developing Colorectal Cancer ObesityObesity Physical inactivityPhysical inactivity Cigarette smokingCigarette smoking Diet high in red or processed meatDiet high in red or processed meat Heavy alcohol consumptionHeavy alcohol consumption Inadequate screeningInadequate screening

5. 50-75% of cancers can be prevented by lifestyle and dietary changes

6. CRC Burden in TN TN = 52.3 (50.5, 54.2)

7. CRC Burden in TN TN = 18.9 (17.8 -20)

8. Disparate CRC Outcomes

9. TN Risk Profile (2007) 13.5% (12.4%) below poverty – 15 th –Median per capita income = $13,282 in Central Appalachia, lowest in the nation 24.1% (19.6%) < HS education – 7 th –9.6% < 9 th grade education (5 th) 31.5% sedentary – 2 nd 67.4% obese (BMI>25) – 4 th –High fat diets, physical inactivity 26.4% (16.3% - 32.5%) consume 5+ fruits/veges per day 24.3% currently smoke (5 th )

10. TN Screening Report (2006) FOBT (>50) –Last 2yrs: 25.6% (12.1 – 26.6%) –Last 1yr: 15.7% (6.6 – 22.5%) Colonoscopy (>50) –Ever: 56.2% (49.8 – 69.2%) –<10yrs: 53.4% (46.6 – 66.4%) –<5yrs: 49.9% (40.6 – 60.9%)

11. Establishment of CRC Screening Guidelines ACS established CRC early detection guidelines in 1980 –1997 – 1 st update –2000 – 2 nd update 1995-2000 Medline data Colorectal Cancer Advisory Committee –2003 - technology update Immunochemical FOBT (iFOBT) added as acceptable screening method –2006 - ACS and US Multi-Society Task Force issued a joint guideline update for postpolypectomy and postcolorectal cancer resection surveillance Follow-up intervals were often too short, increasing cost and potential patient risk –2008 - Virtual Colonoscopy accepted as screening tool Eddy D. CA Cancer J Clin 1980;30:193-240 Smith RA, et al. CA Cancer J Clin 2001:51:38-75 Mysliwiec PA, et al. Ann Intern Med 2004;141:264-271 Ko CW, et al. Gastrointest Endosc 2007;65:648-56

12. CRC Screening Methods Fecal Occult Blood Test (FOBT) –2 samples from each of 3 consecutive stool samples at home –Avoid NSAIDS (7d), Vit C sources (3d), red meat (3d) –Stool sample from DRE is inadequate! Low sensitivity (< 5%) as bleeding often intermittent and blood may not be present in entire stool Sole method of FOBT in up to 33% of PCPs Nadel MR, et al. Ann Intern Med 2005;142:86- 94 –Advantages Cheap, private, no bowel prep Clinical trials show 33% reduction in CRC mortality with proper use; these results may not be realized in community settings because common use of in-office tests and inappropriate follow-up of positive results Nadel MR, et al. Ann Intern Med 2005;142:86-94 Smith RA, et al. CA Cancer J Clin 2001:51:38-75

13. Fecal Immunochemical Test (FIT) Mono/polyclonal antibody detect intact globin protein portion of human Hgb –Specific for globin in LGI tract since globin wont survive passage through UGI tract No cross-reactivity with non-human Hgb or foods Smith A, et al (Cancer 2006) demonstrated sensitivity of 87% for cancer and 43% for high risk adenomas in 2000+ patients –Similar findings by InSure ACS statement: in comparison with guaiac-based test for the detection of occult blood, immunochemical test are more patient-friendly, and are likely to be equal or better in sensitivity and specificity. Less commonly used Levin B, et al. CA Cancer J Clin 2003;53:44-55 Smith A, et al. Cancer 2007;107:2152-2159

14. Endoscopy v. DCBE DCBE –Instilling of barium and air to define colonic mucosa –Less sensitive for subcentimeter lesions –Often used with near-obstructing lesions Flexible Sigmoidoscopy –Veterans Affairs Cooperative Study Group; 3121 patients Exam to splenic flexure detects majority of CRCs but misses >50% of proximal colon cancers Lieberman DA, NEJM 2000;20-162-168 –No need for sedation –Best is combined with FOBT/FIT Colonoscopy –Gold standard when cecum is reached –Risk of perforation –All Roads Lead to Colonoscopy!

15. ACS recommendations for CRC screening in average-risk, asymptomatic people TestFrequency ( starting at age 50) FOBT or FIT*Annually Stool DNA TestInterval uncertain Flex Sig*Q 5 years FOBT + Flex Sig*Annual FOBT/FIT and Flex Sig q 5 years DCBE*q 5 years CT colonographyq 5 years Colonoscopyq 10 years * All positive test should be followed up with colonoscopy. DCBE +/- Flex sig is a suitable alternative.

16. Individuals at increased risk of developing CRC 2x average risk in this population; accounts for 15-20% of colon cancers Whos at increased risk? –h/o of AP/CRC in any 1 st degree relative <60, or >2 1 st degree relatives with h/o AP/CRC of any age (w/o hereditary syndrome) Colonoscopy at age 40 or 10 years before youngest case Repeat q 5-10 years, pending findings –h/o polypectomy and/or resection of CRC

17. Postpolypectomy Surveillance Colonoscopy Recommendations - 2006 Update Small rectal hyperplastic polyps –nl colonoscopy, 10-year f/u –Hyperplastic polyposis syndrome should be screened more frequently <2 small tubular adenomas with LGD –5-10 years 3-10 adenomas, any >1cm, any with villous features or HGD –3 year f/u if completely removed –Subsequent 5 year f/u if nl or above > 10 adenomas –f/u <3 years and consider familial syndrome Piecemeal removal of sessile adenomas –Repeat endoscopy in 2-6 months –After complete removal confirmed, subsequent surveillance based on judgment Winawer SJ, et al. CA Cancer J Clin 2006;56:143-159

18. Postcancer Resection Surveillance Colonoscopy Recommendations - 2006 Update High quality perioperative colonoscopy –Consider CT colonography or DCBE for obstructing lesions Consider colonoscopy 3-6 mo post-op to clear synchronous lesions Colonoscopy within 1 year of perioperative clearance –3-year f/u if this exam nl, then 5 year f/u if 3-year exam nl –For abnormal findings, stratify by risk Consider q3-6 month proctoscopy after LAR x 2-3 years –Independent of surveillance colonoscopies for metachronous disease

19. ACS recommendations for CRC screening among people at high risk Risk CategoryAge to BeginRecommendationComment FH of FAPPubertyEarly endoscopic surveillance and genetic counseling/testing Colectomy for (+) genetic testing FH of HNPCC21Colonoscopy & genetic counseling/testing If genetics (+) or unavailable, colonoscopy; q1-2 years until 40, then annually Inflammatory Bowel Disease 8 years after pancolitis or 12- 15 years after left colitis Colonoscopy with biopsies of dysplasia q1-2 years Prophylactic colectomy for persistent dysplasia Adapted from Smith RA, et al. CA Cancer J Clin 2001:51:38-75

20. Emerging Technology CT (virtual) colonography –May be used in cases of failed or incomplete colonoscopy or in cases of obstructing cancer –Accepted as a screening tool –Medicare will not pay for it –High rate of false positives –Need colonoscopy if positive Stool DNA mutation testing –Uses multicomponent DNA-based stool assay targeting point mutations at hot spots on colon oncogenes (i.e. K-ras, APC, and p53 genes) –Single stool sample needed, DNA shed continuously –Multicenter study by Colorectal Cancer Study Group in average risk patients: Fecal DNA panel v. FOBT Fecal DNA more sensitive in detecting adenomas and cancer, equal specificity –Not yet accepted as a screening tool Large stool collection kits; requires entire stool sample Expensive >$400/test; additional markers increases cost

21. Outreach Efforts (CRC) 2006 = 5, 2007 = 9; 2008 = 5; 2009 = 6 –CRC and skin outreach are least developed programs Colonoscopies: –2006 = 4945; 2008 = 5756 225 new CRC diagnosed 2006 – 2008 –No change in stage distribution

22. Key Points Colon cancer is common in the U.S.Colon cancer is common in the U.S. Prevention and early detection save lives.Prevention and early detection save lives. Everyone over 50 should undergo colon cancer screening as part of annual exam.Everyone over 50 should undergo colon cancer screening as part of annual exam. Education improves screening.Education improves screening.

23. Improving CRC Outcomes Be familiar with CRC screening guidelines Meet people where they are with outreach Target underserved areas Continue to advocate for CRC screening legislation Emphasize prevention/healthy habits Use patient educators, testimonials