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Colorectal Cancer Screening Update

Colorectal Cancer Screening Update. Douglas K. Rex, M.D. Indiana University Medical Center Indianapolis, IN. Colorectal Cancer – Molecular Basis. WHO classification of serrated lesions. Hyperplastic polyps Sessile serrated adenomas (polyps) With cytological dysplasia

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Colorectal Cancer Screening Update

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  1. Colorectal Cancer Screening Update Douglas K. Rex, M.D. Indiana University Medical Center Indianapolis, IN

  2. Colorectal Cancer – Molecular Basis

  3. WHO classification of serrated lesions • Hyperplastic polyps • Sessile serrated adenomas (polyps) • With cytological dysplasia • Without cytological dysplasia • Traditional serrated adenoma

  4. Clinical features of serrated lesions

  5. Colorectal Cancer – Molecular Basis

  6. Flat Lesions – Paris Classification

  7. Pre-cancerous lesions in the colo-rectum: the basics

  8. Pedunculated polyps

  9. Sessile adenomas (1s)

  10. Flat Lesions seen with NBI

  11. Flat lateral spreading tumors

  12. Depressed lesions (Paris type IIc)

  13. Depressed lesion

  14. Flat serrated lesions

  15. Pre-cancerous lesions in the colo-rectum: the basics

  16. Operator dependence – adenoma detection

  17. What is the Adenoma Detection Rate (ADR)? • 2002 USMSTF • Normal colons persons age ≥ 50 y (no resection or IBD) • % of patients with one or more adenomas detected • Targets: ≥ 25% in men and ≥ 15 % in women • Rex et al AJG 2002;97:1296-308 • 2006 ACG/ASGE Task Force • Altered to make the target population screening colonoscopies • Rex et al GIE;2006;63:S16-28

  18. Operator dependence – cancer preventionKaminski et al NEJM2010;362:1795-803

  19. Post-Polypectomy Surveillance (assumes good prep, exam to cecum) CategoryInterval • One or two TA < 1cm 5-10 y • Follow up normal: 5-10 y • 3-10 adenomas, any 3 yvillous component, HGD • Follow up normal: 5y (indefinitely) • > 10 adenomas <3 y • Large sessile adenoma 2-6 mo removed piecemeal Winawer, Gastroenterology 2006

  20. ADR-Interval Interaction High ADR: patients doubly protected Low ADR: patients doubly unprotected Colons are poorly cleared More patients are told they are normal and can return at long intervals • Colons are better cleared • More patients come back at earlier intervals

  21. All Roads Leads to Colonoscopy

  22. How is colorectal cancer screening done in the U.S.? • Colonoscopy √ • FOBT (FIT) √ • Flexible sigmoidoscopy no • Barium enema no • CT colonography no • Fecal DNA testing no

  23. Is there another technology that is better for screening? • Another that is more effective? • Another that is more cost-effective? • Another that costs less? • Another that results in better adherence? • Is there another technology that is less operator dependent?

  24. Is another technology sensitive for serrated lesions?

  25. 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

  26. Variable Performance of FITs Hundt Ann Intern Med 2009;150:162-9

  27. 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

  28. Issues about FIT • Which FITs in the U.S. have the best performance characteristics?

  29. Fecal DNA Tests • 1.0 • APC, k-ras, p 53, DIA, BAT-26 • Imperiale NEJM 2004;351:2704-14 • 1.1 • 1.0 plus gel-based DNA capture and stabilization of DIA • Whitney J Mol Diag 2004;6:386-95 • 2.0 • DIA plus Vimentinhypermethylation • Itzkowitz CGH; 2007;5:111-7

  30. Performance of the Fecal DNA Versions 1.0, 1.1, 2.0 1.0 1.1 2.0

  31. CT colonography • USPSTF declines to recommend coverage • Extracolonic findings • Radiation risk • CMS elects not to cover • No data specific to the elderly • No evidence of increased adherence • Cost analysis not favorable

  32. First RCT of Colonoscopy vs CTCNetherlands (abstract 353;DDW 2011) Colonoscopy: 5,924 invited CTC: 2,920 invited Adherence: 32% Advanced adenomas per 100 participants: 5.2 Advanced adenomas per 100 invitees: 1.7 • Adherence: 21% • Advanced adenomas per 100 participants: • 8.4 • Advanced adenomas per 100 invitees: • 1.7

  33. Serum Assays • Epigenomics (SEPT9) • Europe (EpiproColon) • Asia (mS9 Colon Cancer Assay) • U.S. Quest Diagnostics (ColoVantage) • Oncomethylome • Hypermethylation of SYNE1 and FOXE1 • GeneNews • mRNA expression panel • Phenomenome Discoveries • Gastrointestinal tract acids (GTAs)

  34. Serum Tests • Efficacy • Septin 9 (3 well sensitivity): 51% for localized cancer, 75% for regional cancer, 16% for large adenomas • Does not appear better than FIT • Cost – first charges at $300 • Adherence requirements (abstract 220) • Assumes charge of $150 • More effective than FIT if FIT uptake ≤ 85 % • More cost-effective than FIT if FIT uptake ≤ 60%

  35. Capsule colonoscopy • PillCam 2 • Angle of view 172° from each end • Variable frame speed (4-35 fps) • Requires an extensive bowel preparation • Clear liquids • Full colonoscopy prep • Boosters after small bowel entry • Suppository if colon transit slow

  36. Second generation capsule colonoscopy trials

  37. Can capsule make an impact? Assets Liabilities Prep efficacy Prep acceptability Initial prep Logistics will require 2 preps if positive Cost (Would CMS cover it?) • Non-invasive • Imaging potential • No radiation • No extracolonic findings • Could be done by PCPs • Could be done at home and on weekends – could by pass MDs entirely

  38. Is there evidence of adherence gains?

  39. Less operator dependence than colonoscopy? • Flexible sigmoidoscopy no • Barium enema no • CT colonography unclear • FIT yes • Fecal DNA yes

  40. Is there a better screening test than colonoscopy?

  41. The endoscopist perspective is pre-eminent in the U.S. • Public acceptance of the endoscopic approach rests on evidence of the superior effectiveness of colonoscopy

  42. RR of CRC after colonoscopy in Ontario

  43. Residual risk after colonoscopy:right vs left colon

  44. Residual right colon riskSingh, H et al GASTRO 2010;139:1128-37

  45. Right colon cancers after colonoscopyBaxter et al GASTRO 2011;140:65-72

  46. Polypectomy rates (relative to rates ≤ 10%) – Residual right colon cancer

  47. Right colon protection from colonoscopy • Occurs but is very operator dependent • Is not as great as left-sided protection

  48. Why poor protection in the right colon? • Altered biology • Interval tumors have increased rate of MSI • Interval cancers more likely to be CIMP positive • Technical issues • Poor preparation • Failure to document the cecum • Missing flat and depressed lesions • Missing serrated lesions • Should right colon be retroflexed?

  49. Serrated lesions

  50. Variable detection of proximal colon serrated lesions among GI docs

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