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Update in Colon Cancer Screening

Update in Colon Cancer Screening . Jay R. Levinson, M.D. November 2, 2013. Colon Cancer in U.S. Third most common cancer diagnosed 149,000 new cases annually Lifetime incidence: 5% Second leading cause of cancer death 50,000 deaths annually. Colon Cancer Mortality. Five year survival:

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Update in Colon Cancer Screening

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  1. Update in Colon Cancer Screening • Jay R. Levinson, M.D. • November 2, 2013

  2. Colon Cancer in U.S. • Third most common cancer diagnosed • 149,000 new cases annually • Lifetime incidence: 5% • Second leading cause of cancer death • 50,000 deaths annually

  3. Colon Cancer Mortality • Five year survival: • 90%- localized disease • 68%- regional disease • 10%- metastatic disease • Mortality rates declining (53% of this effect may be due to screening)

  4. Goal of Colon Cancer Screening • To reduce cancer incidence and mortality • Detection of early stage lesions • Detection and removal of precursor lesions

  5. Pathogenesis • Adenoma-carcinoma sequence • Neoplastic changes due to both inherited and acquired genetic defects • Some cancers arise from flat/ depressed “non-polypoid” adenomas • Removal of adenomatous polyps prevents cancer

  6. Colon Polyps • 2/3 of polyps are adenomas- found in 15% of women and 25% of men • Prevalence increases with age • Small distal hyperplastic polyps are innocuous • Risk of CRC increases with adenoma size, number and histology

  7. Colon Polyps • Advanced adenoma: • > 10 mm • villous histology • high grade dysplasia

  8. Right vs. Left • A gradual shift toward right-sided cancers has been noted • Colonoscopy may be more effective in preventing left-sided CRCs • Biology may differ: serrated adenomas more common on the right • These lesions carry BRAF and V600E mutations giving rise to MSI CRCs

  9. Risk FactorsHereditary Syndromes • Familial adenomatous polyposis- 1% of CRCs- nearly 100% develop Ca by age 50 • Variants: Gardner’s syndrome, Turcot’s syndrome, MUTYH-associated polyposis, attenuated APC

  10. Risk FactorsHereditary Syndromes • Lynch syndrome/ HNPCC • 3% of all CRCs, early onset, right-sided • caused by mutations in DNA mismatch repair genes • associated w/ endometrial, ovarian, gastric, duodenal, pancreatico-biliary, renal, brain, skin cancers

  11. Lynch SyndromeDiagnosis • Amsterdam criteria (the 3,2,1 rule): 3 family members, 2 generations, 1 <age 50 • If tumor available, should be tested for MSI and IHC and if compatible- genetic testing • If confirmed Lynch: family members should have colonoscopy every 1-2 years beginning at age 25 or 10 yrs before onset of youngest cancer

  12. Risk Factors • Inflammatory bowel disease: • Ulcerative colitis- 3-15 fold increased risk • Cancers develop in areas of dysplasia rather than from polyps • Crohn’s disease: less risk than UC but still significant if >1/3 of colon involved • Surveillance: annual colonoscopy after 8 yrs of pan-colitis, 12 yrs of left-sided disease

  13. Risk Factors • Abdominal radiation • adult survivors of childhood malignancy treated w/ abdominal radiation are at risk (11 fold) • Colonoscopy every 5 years beginning at age 35

  14. Risk Factors • Race: African Americans • 20% increased mortality, earlier onset, more proximal distribution • ACP: begin screening age 40 • ACG & ASGE: begin screening age 45

  15. Risk Factors • Acromegaly- increased frequency of adenomas and CRC • colonoscopy recommended at Dx • Renal transplantation/immunosuppression- begin screening age 40 or 5 yrs after transplant

  16. Risk Factors • Gender: • CRC mortality 25% higher in men • Adenoma prevalence 10% higher in men • Proximal distribution of CRC in post-menopausal women

  17. Risk Factors • Obesity: • CRC risk increased 1.5 fold • Each 5 mg/m2 increase in BMI increases CRC incidence by 24% in men and by 9% in women

  18. Risk Factors • Smoking and CRC • Incidence: RR 1.18, 95% CI 1.11-1.25 • Mortality: RR 1.25, 95% CI 1.14-1.37 • Incidence of advanced adenomas and serrated polyps also higher

  19. Non-syndromic familial CRC • Family history of colon cancer is present in 10% of all adults but in 25% of cases of CRC • Lifetime risk related to family history ranges from 2-6 fold • All patients should be asked before age 40 about family history to identify risk

  20. Tests for Colon Cancer Screening • Tests that primarily detect cancer • gFOBT • iFOBT/ FIT • sDNA

  21. Fecal Tests • Advantages: • Non-invasive • Inexpensive • Can be done at home

  22. Fecal Tests • Disadvantages: • Non-specific • Poor sensitivity • Do NOT detect most polyps

  23. gFOBT • Guaiac based tests- detect blood in stool via pseudoperoxidase activity of heme • Collect 2 samples from 3 consecutive BMs • Avoid ASA/NSAIDs, red meat, poultry and some cruciferous raw vegetables (false +) • Avoid vitamin C (false -)

  24. iFOBT/ FIT • Detects human globin • More specific than guaiac therefore does not require dietary restriction • More specific for LGI source (globin degraded by digestive enzymes) • Sample collections less demanding/ less direct stool handling

  25. sDNA • Tests for presence of known DNA alterations • Because there is not a single gene mutation, a multitarget assay is required • Multiple markers: 21 separate mutations in K-ras, APC, P53 genes; a probe for BAT-26 (a marker of MSI) and a marker of DNA integrity analysis (DIA) • Requires 30 gm sample

  26. sDNA • Expensive • Non-standardized as yet • Significance of false positive findings unknown as yet

  27. Tests for Colon Cancer Screening • Tests that detect adenomas and cancer • Flex sigmoidoscopy • Colonoscopy • DCBE • CT colography

  28. Flexible SigmoidoscopyAdvantages • Minimal patient preparation (although this limits exam quality) • Does not require sedation • Often performedd by non-specialists • Lower cost than colonoscopy

  29. Flexible SigmoidoscopyDisadvantages • Exam quality variable • Adenoma detection rates significantly lower than colonoscopy • Requires follow up exam with colonoscopy if polyps >5 mm or multiple polyps detected • Patient discomfort • Guidelines require every 5 years • Usage greatly declining

  30. Double Contrast Barium Enema • Has been adopted as an option by ACS, USPSTF, MSGC in 1997 • Visualizes the entire colon • Relatively safe • Only detects 50% of polyps > 1 cm • Use has declined, therefore procedural expertise declining

  31. CT ColographyAdvantages • Comparable to colonoscopy in detecting cancer and large polyps • Minimally invasive (although rectal insufflation of air/ CO2 required) • Radiation exposure/ health risk minimal

  32. CT ColographyDisadvantages • Finding of polyps > 5 mm requires subsequent colonoscopy • False positive rate and lack of consensus on management of small polyps • Cost relatively high • Extracolonic findings often triggers further evaluation with little evidence of benefit

  33. ColonoscopyAdvantages • High sensitivity and specificity • Lesions can be removed at the same procedure

  34. ColonoscopyDisadvantages • Most invasive of the screening tools • Carries a risk of perforation and bleeding • Some polyps difficult to detect due to location: • Studies have questioned how well colonoscopy prevents right sided CRC

  35. Colon Cancer Screening Guidelines • “Menu of options” approach: • Last revised 2008 by a joint committee of the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology • “Preferred strategy” approach: • Proposed by the ACG revised in 2008

  36. Menu of Options- Ave RiskAsymptomatic Adults age > 50 • Cancer prevention tests: • Flex sig every 5 yrs, OR • DCBE every 5 yrs, OR • CT colography every 5 yrs, OR • Colonoscopy every 10 yrs

  37. Menu of Options- Ave RiskAsymptomatic Adults age > 50 • If the flex sig shows a polyp (unless small polyp biopsied as hyperplastic) or if the radiologic tests show more than one polyp or any polyp > 5mm, a colonoscopy is needed.

  38. Menu of Options- Ave RiskAsymptomatic Adults age > 50 • Cancer detection tests: • gFOBT every year, OR • iFOBT every year, OR • sDNA- interval uncertain (?every 2 yrs)

  39. Menu of Options- Ave RiskAsymptomatic Adults age > 50 • If any of the stool tests are positive, this should be followed by a colonoscopy • If the FOBT tests are negative, they need to be repeated ANNUALLY • FOBT done by a single rectal exam in PCP or gyn office do NOT suffice as an adequate screening exam

  40. Menu of Options- Ave RiskAsymptomatic Adults age > 50 • Once an adenoma has been detected and removed, the patient progresses to an adenoma surveillance model with colonoscopy and NOT the initial test that detected the polyp

  41. Preferred Strategy- Ave Risk Asymptomatic Adults age > 50 • ACG recommends a “preferred” strategy to simplify and shorten discussions with patients • Patients more likely to undergo screening with a preferred strategy compared with menu of options; practitioners more likely to follow a simplified approach • Quality colonoscopy is the ACG’s preferred strategy

  42. ACG Current Guidelines Summary • Owing to its high level of effectiveness in CRC prevention and extensive study of outcomes associated with its use, quality colonoscopy every 10 years beginning at age 50 remains the preferred CRC screening strategy

  43. ACG Current Guidelines Summary • Patients who decline colonoscopy, or for whom colonoscopy is unavailable or not feasible should be offered an alternative CRC prevention test (flex sig or CT colography every 5 years) OR the preferred CRC detetion test (FIT)

  44. ACG Current Guidelines Summary • CRC in average-risk persons should begin at age 50 (age 45 in African Americans) • Family history of polyps need not invoke earlier onset or other adjustment of screening unless convincing evidence that the polyps were advanced adenomas

  45. Measures to improve quality and cost-effectiveness of colonoscopy • Bowel preparation should be given in split doses (with half of the dose given on the day of the procedure) • Cecal intubation should be documented by description and photography • All colonoscopists should document adenoma detection rates • Withdrawal times should average at least six minutes (not including biopsy or polypectomy)

  46. Measures to improve quality and cost-effectiveness of colonoscopy • Polyps should be removed by effective techniques, including snaring (rather than forceps methods) for all polyps >5 mm • Piecemeal resecton of large, sessile lesions requires close follow up (3-6 months) • In patients with complete examinations and adequate preparation, recommended screening and surveillance intervals should be followed

  47. Screening Strategies in Patients with Increased Risk- Family Hx • All patients should be asked before age 40 about family history to identify increased risk • Patients at substantially increased risk (those with a 1st-degree relative with CRC or advanced adenoma diagnosed at age <60 OR two 1st degree relatives diagnosed at any age)- screening colonoscopy beginning at age 40 (or 10 yrs younger than earliest diagnosis) and repeat every 5 years • Patients at slightly increased risk (1st degree relative age >60)- screening colonoscopy beginnng age 50 and repeat every 5 years

  48. Surveillance StrategiesPatients with polyps • Small rectal hyperplastic polyps: colonoscopy at average-risk intervals • 1-2 small tubular adenomas: colonoscopy at 5 yrs • 3-10 adenomas, or >1 cm, or villous features, or high grade dysplasia: colonoscopy at 3 yrs • Sessile adenomas: colonoscopy 2-6 months to verify complete removal

  49. Surveillance StrategiesPatients with cancer • Patients undergoing curative resection: colonoscopy at 1 year, if normal then colonoscopy at 3 years and if that exam normal then every 5 years • If the original tumor was obstructing, colonoscopy should be done 3-6 months after resection • Periodic sigmoidoscopy can be done at 3-6 month intervals x 2-3 years after low anterior resection of rectal cancer

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