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