Colon Cancer Screening

1
Colon Cancer Screening
Peter Ahn MD
April 7 2003
2
Clinical Questions

• Q1. Does FOBT reduce mortality from colon cancer?
• Q2. Is colonoscopy superior to flex sig and DCBE
  in reducing mortality from colon cancer?
• Q3. What is the most cost-effective method of
  screening for colon cancer?
• Q4. What is the appropriate age range to screen?
• Q5. What recommendations are made for screening
  high risk patients?

3
Epidemiology

• 2nd leading cause of cancer death in U.S.
• More than 57,000 deaths from colon cancer in 2001
• At age 50
• 5 lifetime risk of diagnosis
• 2.5 risk of death

4
Pathophysiology

• 98 of colon cancers are adenocarcinomas
• More than 80 colon cancers arise from
  adenomatous polyps

5
Screening is important

• Average Pt dying from colon cancer loses 13 years
  of life
• 80 of colon cancers occur in people at average
  risk
• Screening reduces mortality from colon cancer

6
Screening Methods What is available?

• I. Fecal Occult Blood Test (FOBT Hemoccult)
• II. Flexible Sigmoidoscopy (Flex Sig)
• III.FOBT Flex Sig
• IV.Double Contrast Barium Enema (DCBE)
• V. Colonoscopy (CScope)
• What is not available yet
• (CT)
• (Stool DNA)

7
I. FOBT - Test Performance

• Annual FOBT can increase sensitivity to 80
  unrehydrated, 92 rehydrated
• Relative efficacy not tested
• Positive result leads to CScope

8
FOBT - Protocol

• Testing involves 2 samples from 3 consecutive
  stools aimed at detecting pseudoperoxidase found
  in Hgb.
• Diet can interfere but evidence shows that diet
  restriction does not reduce false positives and
  may reduce compliance.
• Immunochemical tests avoid food or drug effects
  but are more expensive and have not been studied
  to clearly show effectiveness.

9
Q1. Does FOBT reduce mortality from colon cancer?
Yes

• 2 European RCTs - biennial screening -
  unrehydrated
• 150,000 and 62,000 Pts
• 15-18 reduction in mortality
• Absolute Risk Reduction in mortality w/biennial
  FOBT 0.8, 1.8 per 1,000
• 1 US RCT - annual screening rehydrated
• 46,000 Pts
• 33 reduction in mortality
• Absolute Risk Reduction in mortality w/annual
  FOBT 4.6 per 1000 w/biennial FOBT 2.9 per
  1000

10
FOBT Pros/Cons

• Pros
• convenient
• non-invasive
• cheap
• Cons
• FOBT fails to detect many polyps and some cancers
  
• false positives lead to invasive testing
• Cost 25

11
Comment on DRE and FOBT

• DRE Digital Rectal Exam
• Fewer than 10 of cancers arise within reach of
  the examining finger
• First test card may miss 42 of cancers detected
  by screening
• Samples may be limited by inadequate stool or
  trauma
• Not recommended as screening for colon cancer

12
II. Flex Sig Test performance

• May identify 70-80 of advanced neoplasms by
  triggering exam of entire colon w/CScope if any
  adenoma found
• Higher risk of proximal advanced polyp or CCa
• Adenomatous polyp 1cm
• Advanced histologic findings
• Multiple polyps

13
Flex Sig - Effectiveness

• Case-control study by Selby Rigid Sig resulted
  in 59 reduction in mortality from CCa within
  reach of Sigmoidoscope
• Similar findings with Flex Sig
• Selby protective effect 6 years

14
Flex Sig - Procedure

• Saline enemas in AM
• No sedation
• 60cm flexible endoscope
• 10 min
• Some abdominal pain

15
Flex Sig Pros/Cons

• Pros
• less intense bowel prep
• less invasive
• less expensive than CScope
• Cons
• does not visualize proximal colon
• invasive
• discomfort, spasm, pain, bleeding
• risk of bowel perforation .01-.02
• Cost 150

16
III. FOBT Flex Sig

• 2 RCTs Adding flex sig to FOBT increased
  detection of 3 to 5 times more large polyps and
  cancers than FOBT alone
• RCT Adding one-time FOBT increased detection
  rate of advanced neoplasm from 70 to 76
• Non-randomized controlled study of 12,000 Rigid
  sigmoidoscopy plus FOBT detected more cancers
  than sigmoidoscopy alone but mortality not
  significantly lower after 9 years
• No RCTs for whether combination of tests more
  effective in lowering mortality.
• FOBT should be done first as a positive result
  will lead directly to CScope

17
FOBT Flex Sig Pros/Cons

• Pros
• likely improve sensitivity of screening over
  either test alone
• Cons
• inconvenience
• cost
• complications of both tests with uncertain gain
  in effectiveness
• Cost 175

18
IV. DCBE Test performance

• Reported Sensitivity 86-90 for CCa/polyps
• Reported Specificity 95
• National Polyp Study paired 862 DCBE and CScope
  studies
• DCBE detected only 48 of polyps gt 1cm
• Specificity of 85

19
DCBE - Effectiveness

• No RCTs examining ability of DCBE to reduce
  incidence or mortality from CCa
• Case-control study 33 reduction in colon cancer
  deaths though CIs were wide

20
DCBE - Procedure

• Prep similar to CScope
• No sedation
• Can be painful

21
DCBE Pros/Cons

• Pros
• widely available
• detects about half of large polyps
• Cons
• sensitivity for large polyps and cancers
  substantially less than CScope
• more likely to identify artifacts (stool)
• cannot remove polyps, non-diagnostic
• follow-up is CScope
• Cost 400

22
V. CScope Test performance

• Performance difficult to evaluate since it is
  considered criterion standard
• Estimated Sensitivity
• 90 for polyps gt1cm
• 75 for polyps lt 1cm
• Specificity difficult to define

23
CScope - Effectiveness

• No RCTs assessing reduction in CCa incidence or
  mortality by CScope alone
• National Polyp Study, 1419 Pts 76-90 of cancers
  could be prevented by regular CScope
• Case-control study of 4411 Veterans CScope
  associated with lower mortality from cancer
  OR0.43

24
CScope - Additional Evidence

• Integral part of trials of FOBT shown to reduce
  colon cancer mortality
• Visualization of neoplasms at least as good as
  Flex Sig AND allows examination of entire colon

25
CScope - Procedure

• Bowel prep day and night before
• Gastrolenterologist or surgeon
• Sedation
• 160cm endoscope
• 30 minutes
• Rate of major complications 0.2-0.3 (bleeding
  1)
• For diagnostic procedures 0.03-0.61 perforation
  risk
• For therapeutic procedures 0.07-0.72 perforation
  risk

26
CScope Pros/Cons

• Pros
• more sensitive
• one-time screening, Dx, Tx possible
• less frequent screening
• Cons
• bowel prep
• sedation
• invasive w/ associated risks
• cost/payment
• providers
• Cost 1400

27
Q2. Is CScope superior to other methods of
screening?

• Accepted as superior, but no direct RCT evidence
  with respect to mortality
• 2 large studies of 3,000 and 2,000 Pts about
  half (52 and 50) of patients with advanced
  proximal neoplasms had no distal colonic
  neoplasms
• New findings suggest flat and depressed adenomas
  account for 22 and 33 of adenomas

28
New tests on the horizon

• CT Colography/ Virtual Colonoscopy
• Thin section helical CT after bowel prep and air
  insufflation creates 2-D and 3-D images
• No studies evaluating the effectiveness of CT
  colography in reducing morbidity or mortality
• Still in research phase to determine test
  performance, effectiveness, costs

29
New tests

• Stool DNA
• Acquired genetic abnormalities drive adenoma to
  carcinoma sequence
• New tests can now recover analyzable human DNA
  from colon via stool to test for abnormalities
• Non-invasive testing of entire colon without
  bowel prep
• Studies underway to further test and refine

30
Q4. When to start / stop screening

• Depends on the population
• For average risk people
• Recommend starting at age 50
• Stop screening at age 80 or when life expectancy
  is less than 5 years
• FOBT effective for ages 50-80
• Beginning screening at age 40 would offer 1-day
  average improvement in life-expectancy
• 83 potential mortality reduction realized by age
  80

31
Who makes recommendations for screening for colon
cancer?

• United States Preventive Services Task Force
  (USPSTF) - 2002
• American Gastroenterologic Association (AGA) -
  2003
• American Cancer Society (ACS) - 2001
• Canadian Task Force on Preventive Health Care
  (CTFPHC) 2001
• Others

32
Average Risk Screening

• Offer screening to men and women starting at age
  50
• Risk stratify
• There are options

33
Algorithm for colon cancer screening
, Either colorectal cancer or adenomatous polyp
, HNPCC hereditary nonpolyposis colorectal
cancer and FAP familial adenomatous polyposis.
34
Screening optionsI. FOBT

• Annually - 2 samples from each of 3 consecutive
  stools
• Test at least biennially for clinical benefit
• Unrehydrated is recommended due to uncertainties
  about effectiveness and cost of rehydrated
  testing

35
II. Flexible Sigmoidoscopy

• Q 5 years
• Based on protective effects shown to last at
  least 6 years

36
II. FOBT Flex Sig

• Annually Q 5 years
• Simply combining two tests

37
IV. DCBE

• Q 5 years
• Recommended interval less than for CScope because
  of lower sensitivity

38
V. CScope

• Q 10 years
• Based on dwell time from adenomatous polyp to
  cancer of at least 10 years
• Cohort of 154 asymptomatic people with negative
  screening Cscope had lt 1 incidence of advanced
  neoplasm at 5 years

39
Average Risk Screening gt 50yo
40
Q3. What is the most cost effective method?

• Average cost-effectiveness ratio values for
  screening with each of the 5 major strategies
  lt 30,000 per life-year saved
• Colonoscopy not proven clearly to be most
  cost-effective screening method
• If willing to pay gt 20,000 per life-year saved
  CScope Q 10yrs or annual FOBT with sigmoidoscopy
  Q 5yrs become favored

41
Familial Risk
1st degree parents, sibs, children. 2nd degree
grandparents, aunts, uncles. 3rd degree
great-grandparents, cousins
42
Q5. Increased Risk - 1

• First-degree relative with colon cancer or
  adenomatous polyp 60yo, or 2 2nddegree
  relatives with colon cancer
• Same screening as for average risk starting at
  40yo

43
Increased Risk - 2

• 2 or more 1stdegree relatives with colon cancer,
  or 1 1stdegree relative with colon cancer or
  adenomatous polyps lt 60yo
• CScope Q 5 yrs at age 40 or 10 years younger than
  earliest diagnosis in the family, whichever comes
  first

44
Increased Risk - 3

• 1 2nddegree, or any 3rddegree relative with
  colon cancer
• Same as average risk

45
High Risk - 1

• Gene carrier or at risk for FAP Familial
  Adenomatous Polyposis
• Sigmoidoscopy annually beginning age 10-12 yo

46
High Risk - 2

• Gene carrier or at risk for HNPCC Hereditary
  NonPolyposis Colorectal Cancer
• CScope Q 1-2 yrs beginning at 20-25yo or 10 yrs
  younger than the earliest case, whichever comes
  first

47
Increased/High Risk Screening
1st degree parents, sibs, children. 2nd degree
grandparents, aunts, uncles. 3rd degree
great-grandparents, cousins
48
Pt preferences, adherence

• Screening rates remain low
• A 1999 survey of US residents gt50yo
• 20.6 had home FOBT within 1 yr
• 33.6 had undergone Sig or CScope within 5 years
• 50-70 of Pts will complete FOBT when advised by
  a clinician

49
Reasons for low screening rates

• Level of public awareness
• Relatively recent consensus on need for screening
• Public and professional attitudes about screening
• Implementation barriers
• Screening guidelines are
  relatively complex

50
Components of successful screening

• Physicians must offer screening
• Pts must accept advice
• Insurers must pay
• Systems must track screening and provide reminders

51
Summary

• Screening for colon cancer reduces mortality
• Screening average risk Pt should begin at age 50
• There are different options available so that
  some form of screening should occur