MCC 2011 - Slide 18

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MCC 2011 - Slide 18

  1. 1. Screening for colorectal cancer Lars Påhlman Dept Surgery, Colorectal unit University Hospital, Uppsala, Sweden
  2. 2. What is screening
  3. 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. 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. 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. 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. 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. 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. 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. 10. A B Detectable by screening Clinically detectable Length biased sampling Time
  11. 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. 12. Time A B C D The disease starts Detectable Clinically presented Death Lead time Lead time bias
  13. 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. 14. Prevention Cure Early diagnosis
  15. 15. Colorectal cancer <ul><li>Prevention </li></ul><ul><li>Changing life style ? </li></ul><ul><li>No </li></ul>
  16. 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. 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>
  19. 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>
  20. 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>
  21. 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>
  22. 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>
  23. 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>
  24. 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>
  25. 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>
  26. 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>
  27. 28. Screening för kolorektal cancer <ul><li>FOBT </li></ul><ul><li>Tumörmarkörer i feaces </li></ul><ul><li>Skopier </li></ul>
  28. 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>
  29. 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>
  30. 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>
  31. 32. FOBT Screening - mortality from CRC Heitson et an. Cochrane Database of Systematic Reviews 2007
  32. 33. FOBT screening - total mortality Heitson et an. Cochrane Database of Systematic Reviews 2007
  33. 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>
  34. 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>
  35. 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>
  36. 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>
  37. 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>
  38. 39. Flex-sig screening - CRC mortality Atkin et al, Lancet 2010
  39. 40. Colorectal cancer - Screening <ul><li>Colonoscopy once ? </li></ul><ul><li>Why not ! </li></ul>
  40. 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>
  41. 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>
  42. 43. Colorectal cancer - Screening <ul><li>FOB - testing </li></ul><ul><li>the only evidence </li></ul><ul><li>based technique ! </li></ul>
  43. 44. Colorectal cancer - Screening <ul><li>How to </li></ul><ul><li>Implement </li></ul><ul><li>FOBT – testing ? </li></ul>
  44. 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>
  45. 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>
  46. 48. Colorectal cancer - Screening <ul><li>Do we know the endpoints ? </li></ul><ul><li>We can use surrogate endpoints </li></ul>
  47. 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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