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MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
MCC 2011 - Slide 18
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MCC 2011 - Slide 18

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  • 1. Screening for colorectal cancer Lars Påhlman Dept Surgery, Colorectal unit University Hospital, Uppsala, Sweden
  • 2. What is screening
  • 3. ‘ The presumptive identification of unrecognised disease or defect by application of tests, examinations or other procedures that can be applied rapidly’ U.S. Commission on Chronic Illness
  • 4. Ideal screening situation <ul><li>Cut - off value </li></ul><ul><li>No disease Disease </li></ul><ul><li> - test + test </li></ul>
  • 5. The common screening situation <ul><li>Cut - off value </li></ul><ul><li> No disease Disease </li></ul><ul><li> - test + test </li></ul>
  • 6. Colorectal cancer - Screening <ul><li>Screening is not a diagnostic test. </li></ul><ul><li>A positive test must in most situations be followed by another test. </li></ul>
  • 7. Colorectal cancer - Screening <ul><li>The disease must be difficult to treat once it is symptomatic. </li></ul><ul><li>There must be advantages with early detection. </li></ul><ul><li>The test must detect pre -clinical lesions </li></ul>
  • 8. Colorectal cancer - Screening <ul><li>High sensitivity ! </li></ul><ul><li>A negative predictive value is important, i.e., to give a correct answer when the test is negative. </li></ul><ul><li>High specificity ! </li></ul><ul><li>Important to avoid false positive test , i.e., reduce unnecessary investigations. </li></ul>
  • 9. Colorectal cancer - Screening <ul><li>Screening does not reduce the incidence. </li></ul><ul><li>Data on survival and stage are difficult to interpret; ( length time bias and lead-time bias ). </li></ul><ul><li>Mortality the ‘true’ endpoint </li></ul><ul><li>Risk for selection bias ( randomised trials preferable). </li></ul>
  • 10. A B Detectable by screening Clinically detectable Length biased sampling Time
  • 11. Length time bias <ul><li> X </li></ul><ul><li>X </li></ul><ul><li>X </li></ul><ul><li>X </li></ul><ul><li>X </li></ul><ul><li>X </li></ul>
  • 12. Time A B C D The disease starts Detectable Clinically presented Death Lead time Lead time bias
  • 13. Lead time bias <ul><li>X </li></ul><ul><li>X </li></ul><ul><li>X </li></ul><ul><li>X </li></ul><ul><li>X </li></ul><ul><li>X </li></ul>
  • 14. Prevention Cure Early diagnosis
  • 15. Colorectal cancer <ul><li>Prevention </li></ul><ul><li>Changing life style ? </li></ul><ul><li>No </li></ul>
  • 16. Colorectal cancer <ul><li>Chemo - prevention ? </li></ul><ul><li>ASA </li></ul><ul><li>Sulindac </li></ul><ul><li>COX - 2 inhibitors </li></ul>
  • 17. Colorectal cancer <ul><li>Cure </li></ul><ul><li>More effective treatment ? </li></ul><ul><li>Yes </li></ul>
  • 18.  
  • 19. Colorectal cancer <ul><li>Early diagnosis </li></ul><ul><li>Screening ? </li></ul><ul><li>Yes </li></ul>
  • 20. Colorectal cancer - Screening <ul><li>Identify risk groups </li></ul><ul><li>Inflammatory bowel disease </li></ul><ul><li>Polyposis coli </li></ul><ul><li>Cancer family syndrome </li></ul><ul><li>Known colorectal cancer </li></ul><ul><li>Known adenomas </li></ul>
  • 21. Colorectal cancer - Screening <ul><li>Inflammatory bowel disease </li></ul><ul><li>Pancolitis and low age at diagnosis </li></ul><ul><li>Family history of colorectal cancer </li></ul><ul><li>Sclerotic cholangitis </li></ul><ul><li>Best prevention is </li></ul><ul><li>Surgery ! </li></ul>
  • 22. Colorectal cancer - Screening <ul><li>Familiar polyposis coli </li></ul><ul><li>All known families in register </li></ul><ul><li>Early endoscopy </li></ul><ul><li>Gene - mapping </li></ul><ul><li>Surgery when adenomas occur </li></ul>
  • 23. Colorectal cancer - Screening <ul><li>Cancer family syndrome HNPCC </li></ul><ul><li>A rare condition ? </li></ul><ul><li>Gene - mapping </li></ul><ul><li>Right - sided colon cancer </li></ul><ul><li>Low age at diagnosis </li></ul><ul><li>Ovarian and uterus cancer </li></ul>
  • 24. Colorectal cancer - Screening <ul><li>Known colorectal cancer </li></ul><ul><li>A ‘clean’ colon perioperatively </li></ul><ul><li>Colonoscopy every 5th year </li></ul><ul><li>Metachronous cancer ( < 3%) </li></ul><ul><li>Selection due to age </li></ul>
  • 25. Colorectal cancer - Screening <ul><li>Known adenomas </li></ul><ul><li>‘ Clean’ the colon once </li></ul><ul><li>‘ High-risk’; - treat as a cancer </li></ul><ul><li>‘ Low-risk’; - no more follow-up </li></ul><ul><li>Selection due to age </li></ul>
  • 26. Colorectal cancer - Screening <ul><li>Known adenomas </li></ul><ul><li>‘ High - risk’ group </li></ul><ul><li>> 3 adenomas </li></ul><ul><li>> 5 hyperplastic polyps in rectum </li></ul><ul><li>Size > 1 cm </li></ul><ul><li>Tubulovillous or villous </li></ul><ul><li>Dysplasia; severe or malignant </li></ul>
  • 27. Colorectal cancer - Screening <ul><li>Known adenomas </li></ul><ul><li>‘ Low - risk’ group </li></ul><ul><li>< 3 adenomas </li></ul><ul><li>< 5 hyperplastic polyps in rectum </li></ul><ul><li>Size < 1 cm </li></ul><ul><li>Tubular </li></ul><ul><li>Dysplasia; mild or moderate </li></ul>
  • 28. Screening för kolorektal cancer <ul><li>FOBT </li></ul><ul><li>Tumörmarkörer i feaces </li></ul><ul><li>Skopier </li></ul>
  • 29. Screening för kolorektal cancer <ul><li>EU rekommenderar screening </li></ul><ul><li>Riktlinjerna FoU </li></ul><ul><li>FOBT ej FoU </li></ul><ul><li>Skopier </li></ul>
  • 30. Colorectal cancer - Screening <ul><li>Faecal occult blood testing </li></ul><ul><li>Low sensitivity </li></ul><ul><li>40 % cancer missed </li></ul><ul><li>80 % adenomas missed </li></ul><ul><li>‘ Late stage’ lesions bleed </li></ul><ul><li>Frequent testing but inexpensive </li></ul>
  • 31. Colorectal cancer - Screening <ul><li>Faecal occult blood testing </li></ul><ul><li>Minnesota - trial USA </li></ul><ul><li>Funen - trial Denmark </li></ul><ul><li>Nottingham - trial UK </li></ul><ul><li>Gothenburg - trial Sweden </li></ul>
  • 32. FOBT Screening - mortality from CRC Heitson et an. Cochrane Database of Systematic Reviews 2007
  • 33. FOBT screening - total mortality Heitson et an. Cochrane Database of Systematic Reviews 2007
  • 34. Colorectal cancer - Screening <ul><li>Faecal occult blood testing </li></ul><ul><li>What do we know from these trials ? </li></ul><ul><li>There is a survival benefit ! </li></ul><ul><li>What type of test ? </li></ul><ul><li>Annually or biannually ? </li></ul>
  • 35. Colorectal cancer - Screening <ul><li>Flexible sigmoidoscopy </li></ul><ul><li>Case-control studies </li></ul><ul><li>J Clin Epidemiol 1988;41:427-34 </li></ul><ul><li>N Engl J Med 1992;326:653-7 </li></ul><ul><li>J Natl Cancer Inst 1992;84:1572-5 </li></ul>
  • 36. Colorectal cancer - Screening <ul><li>Flexible sigmoidoscopy </li></ul><ul><li>Rationale </li></ul><ul><li>Single sigmoidoscopy at age 60 </li></ul><ul><li>5 % of colorectal cancers occur before the age of 50 </li></ul><ul><li>4 % between ages 50-55 years </li></ul>
  • 37. Colorectal cancer - Screening <ul><li>Flexible sigmoidoscopy </li></ul><ul><li>Rationale </li></ul><ul><li>Cancers start as an adenoma </li></ul><ul><li>Small adenomas don't bleed </li></ul><ul><li>Treatment immediately </li></ul>
  • 38. Colorectal cancer - Screening <ul><li>Flexible sigmoidoscopy </li></ul><ul><li>Rationale </li></ul><ul><li>Identify the ‘high’ and ‘low risk’ patient </li></ul><ul><li>Colonoscopy for a ‘high risk’ patient </li></ul><ul><li>Follow the ‘high risk’ group every 5th year </li></ul>
  • 39. Flex-sig screening - CRC mortality Atkin et al, Lancet 2010
  • 40. Colorectal cancer - Screening <ul><li>Colonoscopy once ? </li></ul><ul><li>Why not ! </li></ul>
  • 41. Colorectal cancer - Screening <ul><li>Colonoscopy once </li></ul><ul><li>Incidence Adenomas </li></ul><ul><li>Cancers </li></ul><ul><li> Age 50 60 70 </li></ul>
  • 42. Colorectal cancer - Screening <ul><li>NordICC </li></ul><ul><li>Norway, Sweden </li></ul><ul><li>Poland, Holland </li></ul><ul><li>Baltic states </li></ul><ul><li> 50.000 </li></ul>
  • 43. Colorectal cancer - Screening <ul><li>FOB - testing </li></ul><ul><li>the only evidence </li></ul><ul><li>based technique ! </li></ul>
  • 44. Colorectal cancer - Screening <ul><li>How to </li></ul><ul><li>Implement </li></ul><ul><li>FOBT – testing ? </li></ul>
  • 45. Colorectal cancer - Screening <ul><li>How to continue </li></ul><ul><li>Implement it slowly </li></ul><ul><li>Check quality </li></ul><ul><li>Must be able to evaluate </li></ul><ul><li>Surrogate end - points </li></ul><ul><li>Must be able to stop the process </li></ul>
  • 46.  
  • 47. Colorectal cancer - Screening <ul><li>Stop the experiment </li></ul><ul><li>if the endpoints </li></ul><ul><li>are not reached </li></ul>
  • 48. Colorectal cancer - Screening <ul><li>Do we know the endpoints ? </li></ul><ul><li>We can use surrogate endpoints </li></ul>
  • 49. Colorectal cancer - Screening <ul><li>Surrogate endpoints </li></ul><ul><li>Compliance  60 % </li></ul><ul><li> Pos. pred. value FOB - test  12 % </li></ul><ul><li>Completion rate colonoscopy  85 % </li></ul><ul><li>Complication at colonoscopy  0.02 % </li></ul><ul><li>Stage I or II cancer  55 % </li></ul>

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