Colorectal cancer screening

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Colorectal cancer screening

  1. 1. Update in Colorectal Cancer Screening Douglas K. Rex, M.D. Indiana University Medical Center Indianapolis, IN
  2. 2. Colorectal Cancer – Molecular BasisPathway Frequency Genes MSI Precursor SpeedCIN 65-70% APC No Adenoma Slow K-ras p53Lynch 3% MLH1 Yes Adenoma Fast MLH2 MLH6 PMS2CIMP 30-35% BRAF Sometimes Serrated Can be fast
  3. 3. Minimal Terminology of Serrated Lesions (WHO) § Hyperplastic polyp (HP) § Sessile serrated adenoma/polyp (SSA/P) – With cytological dysplasia – Without cytological dysplasia § Traditional serrated adenoma (TSA)
  4. 4. Therefore§ The WHO recommends that the term “serrated adenoma” always be preceded by a qualifier: – Sessile serrated adenoma/polyp (SSA/P) – Traditional serrated adenoma (TSA)
  5. 5. Features of major categories of serrated lesionsWHO Prevalence Shape Distribution Malignantclassification potentialHyperplastic Very Sessile/flat Mostly distal Very lowpolyp commonSessile Common Sessile/flat 80% proximal Significantserratedadenoma/polypTraditional Rare Sessile/ Mostly distal Significantserrated pedunculatedadenoma
  6. 6. Pathologic differentiation of SSA/P from HP§ HP § SSA/P
  7. 7. SSA/P without and with cytological dysplasia§ SSA/P without § SSA/P with dysplasia dysplasia
  8. 8. 2416 SSA/Ps mean age§ SSA/P 61y§ SSA/P with LGD 66y§ SSA/P with HGD 72y§ SSA/P with cancer 76y • Lash J Clin Pathol 2010;63:681-6
  9. 9. The serrated pathway Hyperplastic polyp ?↓?Sessile serrated adenoma/polyp ↓ probably slowSSA/P with cytologic dysplasia ↓ sometimes fast CIMP colon cancer
  10. 10. So……….§ SSA/P is the main precursor of CIMP-high CRC§ No reliable way to distinguish HP from SSA/P endoscopically • Kimura et al AJG 2012: “Type O” pit§ Agreement for pathologists distinguishing HP from SSA/P is moderate§ Most large serrated lesions in the proximal colon are SSA/P§ SSA/P with cytological dysplasia is a dangerous lesion
  11. 11. Clinical associations of serrated polyps with CIMP-high CRCs§ SSA/P histology (vs hyperplastic)§ Proximal location (vs distal) of serrated lesions§ Size (big vs small) of serrated lesions§ Number (more vs fewer) of serrated lesions
  12. 12. Can screening tests detect serrated lesion ? Sensitivity for serrated lesionsColonoscopy highly variableFIT ?Fecal DNA ?CT colonography ?Flex sig ?Capsule colonoscopy ?Serum assays ?
  13. 13. Colorectal Cancer Screening Tests§ Non-invasive tests § Imaging tests§ gFOBT √ § Colonoscopy √§ FIT √ § Flex sig (seldom§ Fecal DNA used)§ Serum tests § CT colonography (seldom used) § Capsule
  14. 14. How do we achieve excellence in screening?§ Utilize high quality colonoscopists – Should be able to quote ADR – Should see split dose preparations – Should see consistent photographic documentation of cecal intubation – Should see appropriate use of follow up exams§ Switch from gFOBT to FIT – Avoid exams on digital rectals
  15. 15. RCT of FIT vs g-FOBT§ 20,623 screenees§ RCT of FIT (OC- Sensor) vs g-FOBT (HII)§ Adherence 59.6% vs 46.9% (HII)§ Positivity 5.5% vs 2.4% (HII)Van Rossum; GASTRO 2008;135:82
  16. 16. Variable Performance of FITsHundt Ann Intern Med 2009;150:162-9
  17. 17. Performance of the Fecal DNA Versions 1.0, 1.1, 2.0 1.0 1.1 2.0
  18. 18. Septin 9 performance§ 7000 patient sceening trial: manuscript still not published§ 62% sensitivity for cancer – Sensitivity lower for early stage cancer§ No sensitivity for adenomas§ 88% specificity
  19. 19. Fecal DNA testing vs Septin 9 Ahlquist CGH 2012;10:272 Fecal DNA test Septin 9Sensitivity for cancer 91% 50%Stage I-IIISensitivity for cancer 75% 88%Stage IVSensitivity for large 82% 14%adenomasspecificity 93% 73%
  20. 20. CT colonography§ Not approved by the USPSTF – Radiation risk – Extracolonic findings§ Not approved by CMS – Insufficient data in the elderly – Less cost-effective than colonoscopy
  21. 21. First RCT of Colonoscopy vs CTC Netherlands (abstract 353;DDW 2011)§ Colonoscopy: 5,924 § CTC: 2,920 invited§ invited 21% Adherence: § Adherence: 32%§ Advanced adenomas per § Advanced adenomas per 100 participants: 100 participants: – 8.4 – 5.2§ Advanced adenomas per § Advanced adenomas per 100 invitees: 100 invitees: – 1.7 – 1.7
  22. 22. Expected vs actual burden- prep§ Colonoscopy § CTC
  23. 23. Expected vs Actual burden - procedure§ Colonoscopy § CT colonography
  24. 24. Capsule colonoscopy§ Not FDA approved§ PillCam 2 – Angle of view 172° from each end – Variable frame speed (4-35 fps)§ Sensitivity > 80% for polyps ≥ 6mm§ Specificity < 80%§ Requires an extensive bowel preparation
  25. 25. Colonoscopy
  26. 26. Operator dependence of screening tests§ Low (good) § High (bad)§ Fecal DNA § Colonoscopy§ FIT § Flex sig – Commercial variability § CT colonography § Capsule colonoscopy§ ? gFOBT – Interpretation – Digital exams
  27. 27. Flat Lesions – Paris Classification
  28. 28. Pre-cancerous lesions in the colo-rectum: the basicsLesion Paris shape Distribution Prevalence PathologyTraditional 1p Left Low Mostly LGDadenomatouspolyps 1s Throughout Common Mostly LGDFlat 2a Greater to Common Mostly LGDadenomas right(lesions)Sessile 1s or 2a Right colon Common Distinctionserrated from HP mayadenoma not be reliable(polyp)TSA 1s or 1p Left colon rare UncertainDepressed 2c Greater to rare ↑↑HGD and(adenomas) 2a + 2c right invasive CA 2c+ 2a
  29. 29. Residual risk after colonoscopy: right vs left colon
  30. 30. Associations with interval cancers§ Serrated § Other associations§ associationsinterval Features of § Colonoscopy by cancers non-GI doctors – Proximal location § Doctors with low – MSI positive ADRs – CIMP positive § Low cecal intubation rates § Low polypectomy rates § Indication of FOBT
  31. 31. The Adenoma Detection Rate§ % of persons age ≥ 50 undergoing screening colonoscopy with ≥ 1 adenoma detected and removed – Rex et al (USMSTF) 2002 • AJG 2002;97:1296 – Rex et al (ACG/ASGE Task Force on Quality) 2006 • GIE 2006;63:S16
  32. 32. Operator dependence – cancer prevention Kaminski et al NEJM2010;362:1795-803 Adenoma Hazard ratio detection rate (ADR) < 11% 10.94 11.0 14.9% 10.75 15.0-19.9% 12.50
  33. 33. Polypectomy rates (relative to rates ≤ 10%) – Residual right colon cancer
  34. 34. Residual right colon protection Singh, H et al GASTRO 2010;139:1128-37
  35. 35. Right colon cancers after colonoscopy Baxter et al GASTRO 2011;140:65-72
  36. 36. Variable detection of adenomas among GI docs Number of Lowest ADR Highest ADR Range doctorsBarclay 12 9.4% 32.7% 3.5Illinois2006Chen 9 15.5% 41.1% 2.7Indiana2007Imperiale 25 7% 44% 6.3Indiana2009Shaukat 51 10% 39% 3.9Minnesota2009
  37. 37. Variable detection of proximal colon serrated lesions among GI docs Lowest proximal Highest proximal colon Number of colon serrated lesion serrated lesion Range doctors detection rate detection rateHetzel 13 1.1% 7.6% 6.9Boston Kahi 15 1% 18% 18Indiana
  38. 38. What underlies variable detection?§ Training – Lesion recognition – Withdrawal technique – Withdrawal time§ Personality – Poor documentation of procedures§ Visual gaze patterns§ Withdrawal time
  39. 39. Flat adenoma§ White light § Narrow-band imaging
  40. 40. Sessile serrated polyp§ White light § Narrow-band imaging
  41. 41. Serrated lesions
  42. 42. Serrated lesion
  43. 43. Depressed lesion
  44. 44. Depressed lesions
  45. 45. Pseudodepression (2a dip)
  46. 46. Bowel Preparation and Polyp Detection Rates Europe (N=5,832) Adequate Inadequate Completion (%) 90.4 71.1* Time to cecum (min) 11.9 16.1* Withdrawal time (min) 9.8 11.3* Any adenoma 29.4 23.9* Adenoma >1 cm (%) 6.4 4.3* *P<0.05 for all measures. Froehlich et al. Gastrointest Endoscop. 2005;61:378-384.
  47. 47. Split-Dosing Provides More Satisfactory Results Than Traditional Dosing (cont) 60 Group A Group A 90 Group B Group B 76.5 50.7 80 50 44.1 70 39.7 40 56.2 60 32.4 Percent Percent 50 43.8 30 40 19.1 20 30 23.5 20 10 5.5 4.1 4.4 10 0 0 Poor Fair Good Excellent Satisfactory Unsatisfactory Group A = 4 L of PEG on the night before the procedure; Group B = 2 L of PEG on the evening before and 2 L on the morning of the procedure. 47Reprinted from Aoun et al. Gastrointest Endosc. 2005;62(2):213-218.
  48. 48. Efficacy of Suprep in 2 studies§ Study 1 § Study 2OSS PEG-EA OSS PEG-EASuccess Success82.4% 80.3% 97.2% 95.6%Excellent Excellent44.6% 37.3% 63.3% 52.5%Good Good37.8% 43.0% 33.9% 43.2%Fair Fair
  49. 49. The impact of split dosing Not split Split
  50. 50. Arguments Against Split-Dosing Regimens§ Inconvenient to the patient – Unlikely to be a factor once the process is explained to the patient – Patients not more likely to be incontinent en route to the endoscopy unit§ Anesthesiologists will not allow split- dosing – Clear liquids allowed up until 2 hours prior to sedation 50
  51. 51. How do we judge preps?§ Efficacy – Split or same day dosing§ Safety – Sodium phosphate use dramatically decreased – Safe preps: • PEG-ELS (Golytely etc) and SF-ELS (Nulytely) • Sodium sulfate (SuPrep)§ Tolerability –
  52. 52. How to achieve effective preparation§ Split dose all preps§ Low volume preps appropriate for routine patients without severe constipation, on anti-motility agents§ Have fall back approach for patients with clinical factors or proven track record of being hard to prepare§ Discuss importance of preparation in your written instructions
  53. 53. What makes up good detection?§ Bowel preparation§ Adequate time§ Technique: – Looking behind folds – Cleaning up – Adequate distention§ Central gaze in the monitor§ Other factors: – Personality?
  54. 54. Withdrawal technique
  55. 55. Right colon retroflexion
  56. 56. Are there technical solutions to ADR & variable detection?§ Flat lesions Effective? – Chromoendoscopy yes – NBI no – FICE no – iScan limited data – Autofluorescence mixed results – High definition mixed results§ Hidden mucosa – Cap-fitted mixed results – Third-eye maybe
  57. 57. Conclusion regarding technical solutions§ Any gains in detection from technical solutions are much smaller than the variations in detection between examiners using white light§ More study in low detectors needed
  58. 58. Excellence in colonoscopy§ Use effective bowel preparation regimens§ Achieve high cecal intubation rates safely and document with landmarks and photography§ Examine carefully; know the full spectrum of precancerous lesions in the colon – Know your ADR – You should see proximal colon serrated lesions on a regular basis
  59. 59. How do we achieve excellence in screening?§ Utilize high quality colonoscopists – Should be able to quote ADR – Should see split dose preparations – Should see consistent photographic documentation of cecal intubation – Should see appropriate use of follow up exams§ Switch from gFOBT to FIT – Avoid exams on digital rectals

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