1. Screening for colorectal cancers What ’ s new?

2. Screening Routine examination of asymptomatic population of a disease Routine examination of asymptomatic population of a disease Criteria Criteria 1. Important health issue 2. Acceptable treatment a/v 3. Facilities for Dx and Rx a/v 4. Condition can be recognised at early/ latent stage 5. Suitable test for screening a/v 6. Screening test acceptable to population 7. Natural history of disease well understood 8. Agreed policy on whom to treat 9. Cost of dx and rx economically balanced 10. Case finding should be continued

3. Colorectal Cancer Suitable for screening Suitable for screening High incidence among both male and female High incidence among both male and female 2nd most commonly diagnosed cancer and 2nd most common cause for cancer death in Hong Kong* 2nd most commonly diagnosed cancer and 2nd most common cause for cancer death in Hong Kong* Benign adenomatous polyps as premalignant stage Benign adenomatous polyps as premalignant stage Removal of polyps can prevent development into invasive cancer Removal of polyps can prevent development into invasive cancer Treatment for invasive cancer well established Treatment for invasive cancer well established *HK cancer registry 2006

4. What ’ s new? When not to screen? When not to screen? New screening tools New screening tools New guidelines New guidelines

5. Who to screen? Asymptomatic people > 50 years Asymptomatic people > 50 years Start screening earlier for known high risk groups Start screening earlier for known high risk groups Personal history of CRC Personal history of CRC Family history of CRC Family history of CRC Known inheritance of genetic cancer syndromes Known inheritance of genetic cancer syndromes Inflammatory bowel disease Inflammatory bowel disease

6. When not to screen? When harm of screening rises significantly to outweigh the potential benefits When harm of screening rises significantly to outweigh the potential benefits First seen in recommendations in year 2008 First seen in recommendations in year 2008 Consider screening for age 76-85 years for special cases only Consider screening for age 76-85 years for special cases only Cat C recommendation* Cat C recommendation* Do not consider in any case > 85 years Do not consider in any case > 85 years Cat D recommendation* Cat D recommendation* * Screening for colorectal cancer: US precventive services task force recommendation statement

7. Which screening test to use? Colonoscopy 10 yearly preferred Colonoscopy 10 yearly preferred Alternatives Alternatives Flexible sigmoidoscopy 5 yearly Flexible sigmoidoscopy 5 yearly Flexible Sigmoidoscopy 5 yearly with annual FOBT Flexible Sigmoidoscopy 5 yearly with annual FOBT Annual FOBT Annual FOBT * ASGE guidelines :Colorectal cancer screening and surviellance Gastrointestinal Endoscopy 2006;63:546-7 * ASGE guidelines :Colorectal cancer screening and surviellance Gastrointestinal Endoscopy 2006;63:546-7

8. Which screening test to use? USPSTF recommedations 08 Screening tests recommended (Cat A) Screening tests recommended (Cat A) Colonoscopy every 10 years Colonoscopy every 10 years Annual sensitive FOBT/ FIT Annual sensitive FOBT/ FIT Flexible sigmoidoscopy every 5 years with a mid-interval sensitive FOBT/ FIT Flexible sigmoidoscopy every 5 years with a mid-interval sensitive FOBT/ FIT Consider stop screening by 75 years old (Cat C/D) Consider stop screening by 75 years old (Cat C/D) Evidence inadequate to assess benefits and harms of CT colonography and fecal DNA testing Evidence inadequate to assess benefits and harms of CT colonography and fecal DNA testing Ann G. Zauber, Iris Lansdorp-Vogelaar, Amy B. Knudsen, Janneke Wilschut, Marjolein van Ballegooijen, and Karen M. Kuntz Evaluating Test Strategies for Colorectal Cancer Screening: A Decision Analysis for the U.S. Preventive Services Task Force Ann Intern Med. 2008;149:659-669. Ann G. Zauber, Iris Lansdorp-Vogelaar, Amy B. Knudsen, Janneke Wilschut, Marjolein van Ballegooijen, and Karen M. Kuntz Evaluating Test Strategies for Colorectal Cancer Screening: A Decision Analysis for the U.S. Preventive Services Task Force Ann Intern Med. 2008;149:659-669.

9. Which screening test to use? ACS-MSTF recommendations 08 For detecting polyps + cancer For detecting polyps + cancer Colonoscopy 10 yearly Colonoscopy 10 yearly Flexible sigmoidoscopy 5 yearly Flexible sigmoidoscopy 5 yearly DCBE 5 yearly DCBE 5 yearly CT colonography CT colonography For primarily detecting cancer For primarily detecting cancer Annual high sensitivity gFOBT/ FIT Annual high sensitivity gFOBT/ FIT Stool DNA test ? Interval Stool DNA test ? Interval (any positive test would warrant a colonoscopy) (any positive test would warrant a colonoscopy) * Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology CA Cancer J Clin 2008 * Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology CA Cancer J Clin 2008

10. Which screening test to use? Asia Pacific consensus 2008 Screening should start at 50 years Screening should start at 50 years Male sex, smoking, obesity and family history are risks factors Male sex, smoking, obesity and family history are risks factors Recommended tests Recommended tests FOBT (gFOBT or FIT) FOBT (gFOBT or FIT) Flexible sigmoidoscopy Flexible sigmoidoscopy Colonoscopy Colonoscopy DCBE and CT colonography not preferred DCBE and CT colonography not preferred * Asia Pacific Consensus Recommendations for Colorectal cancer screening Gut2008;57:1166-76

11. What new tools in the current update? Immunochemical FOBT (FIT) Immunochemical FOBT (FIT) Fecal DNA testing Fecal DNA testing CT colonography CT colonography

12. Immunochemical FOBT (FIT) Proposed advantage Proposed advantage Detect human globin Detect human globin not subject to false – ve with high dose Vit C not subject to false – ve with high dose Vit C Globin digested in upper GI tract, more specific for lower GI tract bleeding Globin digested in upper GI tract, more specific for lower GI tract bleeding Compare with high senstivity gFOBT Compare with high senstivity gFOBT Similar in sensitivity and specificity Similar in sensitivity and specificity *Allison JE, et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst 2007;99:1462–1470 *Gopalswamy N et al. A comparative study of eight fecal occult blood tests and HemoQuant In patients in whom colonoscopy is indicated. Arch Fam Med 1994;3:1043–1048 *Greenberg PD, et al. A prospective multicenter evaluation of new fecal occult blood tests in patients undergoing colonoscopy. Am J Gastroenterol 2000;95:1331–1338 *Wong BC, et al. A sensitive guaiac faecal occult blood test is less useful than an immunochemical test for colorectal cancer screening in a Chinese population. Aliment Pharmacol Ther 2003;18:941–946 *Smith A, et al. Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia. Cancer 2006;107:2152–2159 *Levi Z, et al. A quantitative immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med 2007;146:244–255

13. Fecal DNA testing Variable reported performance Variable reported performance sensitivity 52-91%, specificity 93-97% sensitivity 52-91%, specificity 93-97% Better than traditional gFOBT Better than traditional gFOBT No conclusive difference with high sensitivity gFOBT/ FIT No conclusive difference with high sensitivity gFOBT/ FIT Issue of positive fDNA but – ve Ix Issue of positive fDNA but – ve Ix Newer version now available in market Newer version now available in market not widely tested not widely tested ?any improvement of performance ?any improvement of performance Best test interval remained unknown Best test interval remained unknown Recommeded by manufacturer to be 5 yearly Recommeded by manufacturer to be 5 yearly *Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 2004;351:2704–2714

14. CT colonography Radiological method to examine the colon Radiological method to examine the colon Multidetector CT scanners with 2D and 3D reconstruction Multidetector CT scanners with 2D and 3D reconstruction Bowel preparation as for colonoscopy Bowel preparation as for colonoscopy Stool and Fluid tagging to reduce false positive rates Stool and Fluid tagging to reduce false positive rates Colonic distension during scan Colonic distension during scan Need training for radiologist for interpretation Need training for radiologist for interpretation

15. CT Colonography Preferred over barium enema Preferred over barium enema Colon proximal to an obstructing lesion Colon proximal to an obstructing lesion incomplete colonoscopy incomplete colonoscopy Accuracy Accuracy Similar to colonoscopy for lesions >10mm Similar to colonoscopy for lesions >10mm (sensitivity 94% specificity 96% for >10mm)* (sensitivity 94% specificity 96% for >10mm)* Inferior for smaller polyps and flat polyps Inferior for smaller polyps and flat polyps (sensitivity 89% specificity 90% for <6mm)* (sensitivity 89% specificity 90% for <6mm)* Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003;349:2191-200

16. CT Colonography Outstanding issues Outstanding issues reporting of polyps 5 mm or smaller reporting of polyps 5 mm or smaller threshold polyp size for colonoscopy referral threshold polyp size for colonoscopy referral intervals for repeated examinations intervals for repeated examinations radiation exposure radiation exposure extra-colonic findings and implications extra-colonic findings and implications Reported 7-15% of CT colonographies Reported 7-15% of CT colonographies - ASGE Techology Committee Update on CT colonography Gastrointestinal endoscopy 2009 Vol 69 No 3 - USPSTF recommendation statement 2008 - ASGE Techology Committee Update on CT colonography Gastrointestinal endoscopy 2009 Vol 69 No 3 - USPSTF recommendation statement 2008

17. Recommendations TestsACSMSTFUSPSTF USPSTF modeling Other modeling Asia Pacific Consensus Traditional gFOBT NYsuboptimalmixedY Sensitive gFOBT/FIT YYYYY fDNA 5 yearly Y insufficient evidence not evaluated suboptimal FS 5 yearly YYsuboptimalsuboptimalY CTC 5 yearly Y insufficient evidence not evaluated Y not preferred C ’ scope 10 yearly YYYYY

18. Recommendations TestsACSMSTFUSPSTF USPSTF modeling Other modeling Asia Pacific Consensus Traditional gFOBT NYsuboptimalmixedY Sensitive gFOBT/FIT YYYYY fDNA 5 yearly Y insufficient evidence not evaluated suboptimal FS 5 yearly YYsuboptimalsuboptimalY CTC 5 yearly Y insufficient evidence not evaluated Y not preferred C ’ scope 10 yearly YYYYY

19. Recommendations TestsACSMSTFUSPSTF USPSTF modeling Other modeling Asia Pacific Consensus Traditional gFOBT NYsuboptimalmixedY Sensitive gFOBT/FIT YYYYY fDNA 5 yearly Y insufficient evidence not evaluated suboptimal FS 5 yearly YYsuboptimalsuboptimalY CTC 5 yearly Y insufficient evidence not evaluated Y not preferred C ’ scope 10 yearly YYYYY

20. Recommendations TestsACSMSTFUSPSTF USPSTF modeling Other modeling Asia Pacific Consensus Traditional gFOBT NYsuboptimalmixedY Sensitive gFOBT/FIT YYYYY fDNA 5 yearly Y insufficient evidence not evaluated suboptimal FS 5 yearly YYsuboptimalsuboptimalY CTC 5 yearly Y insufficient evidence not evaluated Y not preferred C ’ scope 10 yearly YYYYY

21. Recommendations TestsACSMSTFUSPSTF USPSTF modeling Other modeling Asia Pacific Consensus Traditional gFOBT NYsuboptimalmixedY Sensitive gFOBT/FIT YYYYY fDNA 5 yearly Y insufficient evidence not evaluated suboptimal FS 5 yearly YYsuboptimalsuboptimalY CTC 5 yearly Y insufficient evidence not evaluated Y not preferred C ’ scope 10 yearly YYYYY

22. Take Home Message Different recommendations for colorectal screening Different recommendations for colorectal screening Most consistently recommended for screening of colorectal cancer Most consistently recommended for screening of colorectal cancer Colonoscopy 10 yearly Colonoscopy 10 yearly High sensitivity gFOBT/ FIT yearly High sensitivity gFOBT/ FIT yearly New technology coming up New technology coming up Stool DNA Stool DNA CT colonography CT colonography