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Colorectal Cancer Screening for Family Physicians - What's New

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Colorectal cancer is the the most common cancer in Singapore and in many developed countries. The past decade has seen many countries implement colorectal cancer screening programs to decrease its mortality. Established cancer programs utilize tests such as fecal occult blood and colonoscopy to detect colorectal cancer in its early stages or even in its precancerous adenoma stage. Studies in recent years reinforce the benefit, accuracy and risks of these screening modalities. Nonetheless, screening rates remain suboptimal. The past 5 years have seen many new advances in colorectal cancer screening, including new screening modalities. Of these, 3 new modalities have already been approved by the US FDA and in various parts of the world. There are: stool DNA test, blood septin 9 test, and capsule colonoscopy. We discuss about these new developments in colorectal cancer screening and how they may impact our practice in the near future.

Publié dans : Santé & Médecine
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Colorectal Cancer Screening for Family Physicians - What's New

  1. 1. Colorectal Cancer (CRC) Screening for the Family Physician What’s New? Dr Jarrod Lee Gastroenterologist & Advanced Endoscopist 1
  2. 2. 2 Scope • Rational for CRC Screening • New Data, Current Tests • New Screening Tests • New Guidelines 2
  3. 3. The Rationale for CRC Screening • CRC is a major public health problem; screening lowers morbidity and mortality • Most (>80%) occur in average risk individuals; screening should be applied to general population • No reliable early symptoms; screening is only way for early detection • Natural history favours screening: • Precancerous stage (adenoma) progress slowly to cancer • Adenomas can be removed to prevent cancer 3
  4. 4. Natural History of CRC 41. Amersi et al. 2005. 2. Zauber et al. 2012
  5. 5. CRC Development Pathway 5
  6. 6. Sessile Serrated Adenomas • Cause up to 1/3 of CRC • Do not bleed • Hard to detect 6
  7. 7. Likelihood of Adenoma to Contain CRC or HGD 7Pickhardt et al. 2010
  8. 8. National Polyp Study: CRC Incidence 8Winawer et al. 1993.
  9. 9. National Polyp Study: CRC Mortality 9Zauber et al. 2012
  10. 10. New Data, Current Tests 10
  11. 11. 11 Stool FIT
  12. 12. Annual FIT • Mortality benefit for gFOBT proven by large pragmatic RCTs • Reduces CRC specific mortality by 9-22% • FIT more sensitive than gFOBT • Sensitivity: 73-88% for CRC, 22-40% for AA • Specificity: 91-96% for CRC, 91-97% for AA • Does not require bowel preparation • Limited compliance: 53-67% 12
  13. 13. 13 CT Colonography (CTC)
  14. 14. CT Colonography (CTC) • Diagnostic accuracy: • Sensitivity: 67-94% for AA; 73-98% for polyps > 5mm • Specificity: 86-98% for AA; 80-93% for polyps > 5mm • Flat polyps will be missed • Sensitivity lower without bowel preparation • Risks: • Perforation: 2 per 10,000 scans • Ionizing radiation dose 1-7 mSv • Extracolonic findings: 5-37% need further diagnostic work up, < 3% need definitive treatment 14
  15. 15. Colonoscopy 15
  16. 16. Colonoscopy • Sensitivity: 89-98% for AA; 75-93% for polyp > 5mm • Mortality benefit for flexible sigmoidoscopy proven by large pragmatic RCTs • Risks: • Perforation and major bleeding • 12 per 10,000 screening colonoscopies • Overdiagnosis and overtreatment of smaller lesions • Highly operator dependent 16
  17. 17. Operator Factors 17
  18. 18. Poor Bowel Preparation • Higher rate of missed lesions: • Per adenoma miss rate 47.9% (18% high risk) • Minimum standard for CRC screening program: • 90% good preparation (Target: 95%) 18
  19. 19. Endoscopist factors proven in several important studies •1% increase in ADR  3% decrease in CRC mortality 19
  20. 20. 20
  21. 21. What’s New? 21
  22. 22. Stool DNA Test 22
  23. 23. Overview of Stool DNA 23
  24. 24. Biological Basis of Stool DNA 24
  25. 25. Cologuard • FDA approval Aug 14 based on pivotal DeeP-C study • Subsequent studies with similar design showed similar results: Alaska and Netherlands studies • Automated assay for tumour related DNA changes 25
  26. 26. Cologuard Biomarkers 26
  27. 27. 27
  28. 28. 28
  29. 29. • Pivotal Study: DeeP-C Trial • 10,000 average risk asymptomatic patients • Cologuard vs FIT; colonoscopy as reference • Overall CRC sensitivity 92.3%, specificity 86.6% 29
  30. 30. CRC and AA Detection 30
  31. 31. Advanced Adenoma Sensitivity 31
  32. 32. Evolution of Stool Tests 32
  33. 33. 33 Septin 9 Test
  34. 34. The SEPT9 Gene • Septins: • Multifunctional ‘scaffolding’ proteins that provide structural support during cytokinesis • SEPT9 gene produces septin-9 • Appears to act as a tumour suppressor • Active in cells throughout body • In CRC cells: SEPT9 gene is hypermethylated and the DNA is released into peripheral blood • Methylated SEPT9 DNA can be detected by PCR 34
  35. 35. 35
  36. 36. Outcomes • PRESEPT: 7941 patients vs colonoscopy • CRC: sensitivity 68%; specificity 80% • Advanced polyps: sensitivity 21% • FIT comparison study: 301 patients vs FIT • CRC sensitivity: 73% vs 68% • CRC specificity: 81% vs 97% • Admit study • 420 patient noncompliant with screening guidelines • 99.5% adherence 36
  37. 37. FDA Approval April 2016 • Controversial decision; voting as follows: • Test is safe: 9 yes; 1 abstain • Test is effective: 5 yes; 6 no • Benefits outweigh risks: 5 yes; 4 no; 1 abstain • Main concern was failure to outperform FIT • Approved for CRC screening in average risk patients who refuse FIT or colonoscopy • Potential to increase overall participation rates 37
  38. 38. 38
  39. 39. China CRC Screening Guidelines In 2015 National Guidelines, recommended as the ‘standard’ test with FOBT for CRC screening. 39
  40. 40. In Practice • Easy to participate; no diet preparation or medication alteration required • Effective for CRC at all stages, and at all sites • Colonoscopy required if positive • Performed annually if negative 40
  41. 41. Colon Capsule 41
  42. 42. 2nd Generation Colon Capsule • 2 video cameras: • 172 degrees each • 4 images per second • Battery: >10H • Wireless Transmission • Adaptive frame rate (AFR) • Activated in small bowel • Stationary: 4 fps; Moving: 35 fps • Detects 85-90% more polyps (compared to PCC1) 42
  43. 43. PillCam Colon (PCC) 2 In Practice • Bowel preparation crucial • Need to use ‘boosters’ • Completion rate >90% • Complications: • Capsule retention 1% • Related to bowel preparation • Contraindications: same as small bowel capsule 43
  44. 44. 44
  45. 45. Official Recommendations • FDA approval in 2012: • Only after incomplete colonoscopy • Patients should be able to undergo colonoscopy if a clinically significant abnormality is found • EU approval in 2006 • ESGE guidelines 2012: • Feasible and safe and appears to be accurate when used in average risk individuals (Evidence level 2++, grade C recommendation) • No formal role in CRC Screening as yet 45
  46. 46. 46 • 1292 patients with PCC2 vs colonoscopy • Polyps > 6mm – Sensitivity 86% – Specificity 88.1% • Polyps > 10mm – Sensitivity 87% – Specificity 95.3% • Cancers: 100%
  47. 47. CCE vs CTC • Few studies to date • Spada et al. Gut 2015. • 100 patients with incomplete colonoscopy • Polyps > 5mm: CCE 24.5% vs CTC 12.2% • Polyps > 10mm: CCE 5.1% vs CTC 3.1% • Relative sensitivity 1.67 – 2.0 • Rondonotti et al. Clin Gastro Hepatol 2014 • 66 patients with positive FIT • Similar sensitivity 88% for polyps > 5mm • 78% preferred CCE to CTC 47
  48. 48. The Future • 3D visualization • Panaromic visualization • Automatic detection: current accuracy for polyps: >90% 48
  49. 49. Cloud Based Data Management 49
  50. 50. 50 New Guidelines 2016
  51. 51. New Guidelines 2016 • USPSTF Guidelines published JAMA 2016 • “Screening tests are not presented in any preferred or ranked order” • “Goal is to maximize the total number of persons who are screened because that will havethe largest effect on reducing colorectal cancer deaths” 51
  52. 52. Life Years Gained per 1000 Invidividuals Screened 52
  53. 53. CRC Deaths Averted per 1000 Individuals Screened 53
  54. 54. Complications of CRC screening Per 1000 Individuals Screened 54
  55. 55. Recommendations • Start CRC screening at 50 years, stop at 75 years • Screening for 75-85 years should be individualized • Numerous screening tests available • No head to head studies to demonstrate any test to be more effective • Clinicians should engage patients in informed decision making about the screening strategy • Patient’s preference • High adherence over time 55
  56. 56. 56
  57. 57. Conclusion • CRC Screening is effective • New data reinforces current tools • New tools offer promise • CRC screening will continue to evolve 57
  58. 58. Thank You 58

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