describing role and modalities of screening in colorectal cancers

1. COLORECTAL CANCER SCREENING: BENEFITS
AND CHALLENGES
Dr. Ashutosh Mukherji
Additional Professor
Department of Radiotherapy,
Regional Cancer Centre, JIPMER

2. Prevalence: CRC is 3rd
in Cancer
Incidence & Mortality in Both Sexes
~140k
new cases
each year
~50k
yearly
deaths
Lifetime risk of CRC diagnosis in US is 5% (1 in 20)

3. Racial Disparities in CRC
Mortality
African Americans have 20% higher
incidence and 45% higher mortality
from CRC than whites

5. Essentials of Effective
Screening
Prevalence
Reduction in Morbidity/Mortality
Sensitivity, Specificity, Reliability
Reasonable Cost
Low Risk from Screening Test

6. Reduction in Morbidity/Mortality:
Polypectomies Prevent Carcinomas
10%
⅓
96%
adenomas progress
to colorectal cancer
of colorectal cancers develop
from adenomatous polyps
over a period of 10-15 years
of adults develop ≥ 1 polyps by
age 50, this increases with age Early detection & removal
of polyps eliminates the
possibility they become
cancerous.
Routine screening could save ~19,000 lives per year

7. Genetic Model of Colorectal Cancer
Bat-26
(Sporadic)
p53
Late
Adenoma
Optimum phase for
early detection
Many decades
APC K-ras
Mutation
Bat-26
(HNPCC)
Courtesy of Barry M. Berger. MD, FCAP EXACT Sciences
Late
Cancer
Early
Cancer
Adenoma
Normal
Epithelium
Dwell Time: 2-5 years 2-5 years

8. Quantifying risk of CRC
(NHMRC Guidelines
2005)
If age is 5 years
Risk
10 years
Over
15 years 20 years
30 1 in 7000 1 in 2000 1 in 700 1 in 350
40 1 in 1200 1 in 400 1 in 200 1 in 90
50 1 in 300 1 in 100 1 in 50 1 in 30
60 1 in 100 1 in 50 1 in30 1 in 20
70 1 in 65 1 in 30 1 in 20 1 in 15
80 1 in 25 1 in 25

9. Quantifying risk based on
family history of CRC
(NHMRC Guidelines 2005)
RR
• No family history of CRC 1
• One 1o
relative CRC >55 2
• One 2o
relative CRC 1.5
• One 1o
relative CRC <55 3-6
• Two 1o
or one 1o
and one 2o
relative
CRC at any age 3-6

10. Quantifying risk based on
family history of CRC
(NHMRC Guidelines 2005)
If age is 5 years
Risk
10 years
Over
15 years 20 years
30 1 in 7000 1 in 2000 1 in 700 1 in 350
40 1 in 1200 1 in 400 1 in 200 1 in 90
50 1 in 300 1 in 100 1 in 50 1 in 30
60 1 in 100 1 in 50 1 in30 1 in 20
70 1 in 65 1 in 30 1 in 20 1 in 15
80 1 in 25 1 in 25

11. ACS 2003 CRC Prevention and
Early Detection Recommendations
• Fecal Occult Blood Testing (FOBT)
– Guaiac
– Immunochemical
• Flexible Sigmoidoscopy (FSIG)
• FSIG + FOBT
• Colonoscopy
• Double Contrast Barium Enema (DCBE)

12. Colonoscopy is considered the GOLD
STANDARD for the detection of neoplastic
lesions at risk of progression to CRC and is
recommended as a first-line screening
test in average and high-risk populations.
12

13. Category 1: Those at or
slightly above average
risk
• No personal history of bowel cancer,
advanced adenoma or chronic ulcerative
colitis
• Either no close relatives with CRC or one 1o
OR 2o
relative diagnosed >55

14. Category 2: Those at
moderately increased
risk
• One 1o
relative CRC <55
• Two 1o
relatives or one 1o
and one 2o
relative
on the same side of the family CRC diagnosed
at any age

15. Screening
recommendation for
Category 1 patients
• Faecal occult blood testing (FOBT) every
second year from the age of 50 years (NBCSP)
– ie NOT all patients with a first degree relative
with CRC qualify for colonoscopic screening

16. Screening
recommendation for
Category 2 patients
• Colonoscopy
• Every 5 years
• Starting at age 50, or ten years younger than
the age of first diagnosis in the family,
whichever comes first

17. Category 3: Those at
potentially high risk
• Three or more 1o
and 2o
relatives on the same side of
the family with CRC (suspect HNPCC)
• Two or more 1o
and 2o
relatives on the same side of
the family with CRC and one or more of the
following features
– Multiple cancers in one person
– CRC before the age of 50 years
– Another relative(s) with related malignancy
• Endometrium, ovary, stomach, small bowel, renal pelvis, ureter,
biliary tract or brain

18. Category 3: Those at
potentially high risk
• At least one 1o
relative with a large number of
adenomas throughout the large bowel
(suspected FAP)
• A relative in whom the presence of high risk
mutation in the adenomatous polyposis coli
(FAP) or one of the mismatch repair genes
(HNPCC) has been identified

19. Screening
recommendations for
Category 3 patients
• FAP suspected
– Flexible sigmoidoscopy annually (+/- dye spray chromoendoscopy or
narrow band imaging) from 12-15 years to 30-35 years
– Genetic testing for mutation on Chromosome 5q
• If positive,
– prophylactic total colectomy and ileorectal anastomosis or
restorative proctocolectomy and ileal pouch anal anastomosis
– Annual endoscopy of upper GI and Rectum or pouch for life

20. Screening
recommendations for
Category 3 patients
• HNPCC suspected
– Genetic testing for HNPCC
• Immunohistochemistry or MSI testing of family members’ cancers and
polyps, then gene testing if positive
• If gene mutation established, genetic testing of family members
• If positive
– Yearly colonoscopy
– Regular assessment of other organs
– If cancer found, change of surgical approach
• More extensive colectomy
– ? Prophylactic colectomy
• If negative, ??

21. SURVEILLANCE OF
OTHER HIGH RISK
GROUPS
• Past personal history of CRC, repeat
colonoscopy to be performed
– If colonoscopy incomplete before surgery,
between 3 and 6 months post op
– If colonoscopy complete pre-op, 3 years after
surgery (?? 1 year)
– Every 3 years unless symptoms or adenomatous
polyps found

22. SURVEILLANCE OF
OTHER HIGH RISK
GROUPS
• Past personal history of adenomatous
polyps, repeat colonoscopy at
– 1 year if multiple polyps, poor bowel prep or
potentially incomplete resection of adenoma
– 3 years if large adenoma (>1cm), or those with
villous change
– 4-6 years if none of above risk factors

23. SURVEILLANCE OF
OTHER HIGH RISK
GROUPS
• Long standing ulcerative colitis
– Colonoscopic surveillance every 2 years with
multiple biopsies (for dysplasia) starting ~8 years
after diagnosis

24. SCREENING OF THE
AVERAGE RISK
POPULATION
• Faecal occult blood test every 2 years
starting at age 50
– Immunological test (tests for human
haemoglobin)
• National Bowel Cancer Screening Program

25. Screening Patients With a Family History
• If patient has either:
– CRC or adenomas* in
a first-degree relative
diagnosed at age >60
OR
– Two second-degree
relatives with CRC
Begin screening at age
40 with any test
recommended for
average risk; repeat at
usual intervals based
on type of test and
findings.**
*Our expert opinion is that this applies to relatives with advanced adenomas (adenomas that are >1cm, villous, or with high-grade
dysplasia) only, recognizing that this information is often unavailable.
**The evidence base for these guidelines was not strong and some aspects are controversial.
Source: Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline
from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology

26. Screening Patients With a Family History
• If patient has either:
– CRC or adenomas* in a
first-degree relative
diagnosed before age
60 OR
– Two or more first-
degree relatives
diagnosed at any age
(with family history not
suggestive of genetic
syndrome)
*Our expert opinion is that this applies to relatives with advanced adenomas (adenomas that are >1cm, villous, or with high-grade
dysplasia) only, recognizing that this information is often unavailable.
**The evidence base for these guidelines was not strong and some aspects are controversial.
Source: Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline
from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology
Colonoscopy every
5 years starting at
age 40, or 10 years
before the youngest
case in the family
was diagnosed,
whichever comes
first.**

27. Surveillance of Patients with Adenomas at
Prior Colonoscopy
• Low-risk
adenomas*
– 1–2 tubular
adenomas <10mm
Colonoscopy in 5-10
years
*These recommendations assume that the prior colonoscopy was complete and adequate. For serrated polyps, see
Surveillance of Patients with Serrated Polyps at Prior Colonoscopy.
Guidelines for Colonoscopy Surveillance After Screening and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colore

28. • High-risk adenomas*
– 3–10 adenomas
<10mm OR
– >1 adenoma >10mm
OR
– >1 adenoma with
villous features OR
– >1 adenoma with high
grade dysplasia
– >10 adenomas
Surveillance of Patients with Adenomas at
Prior Colonoscopy
Colonoscopy in 3
years
*These recommendations assume that the prior colonoscopy was complete and adequate. For serrated polyps, see
Surveillance of Patients with Serrated Polyps at Prior Colonoscopy.
Guidelines for Colonoscopy Surveillance After Screening and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colore
Colonoscopy in <3
years (consider
syndrome)

29. Surveillance of Patients with Adenomas at
Prior Colonoscopy
• Any adenoma with
piecemeal or
possibly incomplete
excision
*These recommendations assume that the prior colonoscopy was complete and adequate. For serrated polyps, see
Surveillance of Patients with Serrated Polyps at Prior Colonoscopy.
Guidelines for Colonoscopy Surveillance After Screening and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colore
Colonoscopy in 2-6
months

30. Recommendations for Adenoma Surveillance
After First Surveillance Colonoscopy
Baseline
Colonoscopy
Finding
First Surveillance
Colonoscopy
Finding
Interval for
Second
Surveillance
(years)
Low-risk adenoma
(LRA)
• HRA
• LRA
• No adenoma
• 3
• 5
• 10
High-risk
adenoma (HRA)
• HRA
• LRA
• No adenoma
• 3
• 5
• 5
Guidelines for Colonoscopy Surveillance After Screening and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colore

31. A Tale of Three Guidelines:
All Were Published in 2008
• American Cancer Society/US Multi-society
Task Force on Colorectal Cancer/American
College of Radiology (ACS/USMSTF/ACR)
• Kaiser Permanente Care Management
Institute (KPCMI)
• US Preventive Services Task Force (USPSTF)

32. Everyone Agrees, Screening for
Colorectal Cancer Should Begin
at Age 50
What Isn’t Currently Agreed Upon:
•At what age should screening end?
• Which screening methods are
preferred?

33. Modality USPSTF KPCMI ACS/USMSTF/ACR
Standard
gFOBT
✗
✗
least preferred due to low sensitivity &
low compliance
✗
HS-gFOBT/FIT
✔ Q1
✔ Q1-2
no evidence of incremental benefit if
normal colonoscopy in last 10 yrs
✔ Q1
FSIG ✔ Q5
with HS-gFOBT Q3
✔Q10
+/- HS-gFOBT/FIT
✔ Q5
Q10 In high-quality centers, regular
insertion beyond 40cm (splenic flexure)
with good bowel prep;
+/- annual HS-gFOBT/FIT
Colonoscopy
✔ Q10 ✔ Q10 ✔Q10
CTC ✗
insufficient evidence
✗
insufficient evidence to support over
other screening tests
✔Q5
comparable to optical colonoscopy with
state-of-the-art techniques; repeat
interval has not been studied
sDNA ✗
insufficient evidence
✗
insufficient evidence to support over
other screening tests
✔
high sensitivity, interval uncertain
(one manufacturer recommends Q5 but
insufficient data to support)
DCBE
was not considered;
substantially lower sensitivity, not
been subjected to screening trials,
use is declining
✗
insufficient evidence to support over
other screening tests
✔ Q5

34. Modality
USPSTF
Recommended?
Standard
gFOBT
✗
HS-gFOBT/FIT
✔ Q1
FSIG ✔ Q5
with HS-gFOBT Q3
Colonoscopy
✔ Q10
CTC ✗
insufficient evidence
sDNA ✗
insufficient evidence
DCBE
was not considered;
substantially lower sensitivity, not been
subjected to screening trials, use is
declining
 between ages 50-75
years old, all are
equally effective in life-
years gained
(assuming 100%
adherence)
 against routine
screening in adults 76-
85 years old
 strategies differ in total
number of
colonoscopies required
to gain similar numbers
of life-years
USPSTF

35. Modality
KPCMI
Recommended?
Standard
gFOBT
✗
least preferred due to low sensitivity &
low compliance
HS-gFOBT/FIT ✔ Q1-2
no evidence of incremental benefit if
normal colonoscopy in last 10 years
FSIG ✔Q10
+/- HS-gFOBT/FIT
Colonoscopy ✔ Q10
CTC
✗
insufficient evidence to support over
other screening tests
sDNA
✗
insufficient evidence to support over
other screening tests
DCBE
✗
insufficient evidence to support over
other screening tests
with history of
routine screening,
discontinue at 75
without history of
routine screening,
discontinue at 80
this study also
includes screening
recommendations
for those at
increased risk of
CRC
KPCMI

36. Modality
ACS/USMSTF/ACR
Recommended?
Standard
gFOBT
✗
HS-gFOBT/FIT
✔ Q1
FSIG
✔ Q5
Q10 In high-quality centers, regular
insertion beyond 40cm (splenic flexure)
with good bowel prep;
+/- annual HS-gFOBT/FIT
Colonoscopy
✔Q10
CTC
✔Q5
comparable to optical colonoscopy with state-
of-the-art techniques; repeat interval has not
been studied
sDNA
✔
high sensitivity, interval uncertain
(one manufacturer recommends Q5 but
insufficient data to support)
DCBE ✔ Q5
 do not specify age
to discontinue
screening
 if colonoscopy is
contraindicated due
to life-limiting co-
morbidity neither
CTC nor any other
screening tests are
appropriate
ACS/USMSTF/A
CR

37. Modality USPSTF KPCMI ACS/USMSTF/ACR
Standard
gFOBT
✗
✗
least preferred due to low sensitivity &
low compliance
✗
HS-gFOBT/FIT
✔ Q1
✔ Q1-2
no evidence of incremental benefit if
normal colonoscopy in last 10 yrs
✔ Q1
FSIG ✔ Q5
with HS-gFOBT Q3
✔Q10
+/- HS-gFOBT/FIT
✔ Q5
Q10 In high-quality centers, regular
insertion beyond 40cm (splenic flexure)
with good bowel prep;
+/- annual HS-gFOBT/FIT
Colonoscopy
✔ Q10 ✔ Q10 ✔Q10
CTC ✗
insufficient evidence
✗
insufficient evidence to support over
other screening tests
✔Q5
comparable to optical colonoscopy with
state-of-the-art techniques; repeat
interval has not been studied
sDNA ✗
insufficient evidence
✗
insufficient evidence to support over
other screening tests
✔
high sensitivity, interval uncertain
(one manufacturer recommends Q5 but
insufficient data to support)
DCBE
was not considered;
substantially lower sensitivity, not
been subjected to screening trials,
use is declining
✗
insufficient evidence to support over
other screening tests
✔ Q5

38. Many Available Screening
Modalities
Flexible Sigmoidoscopy
(FSIG)
Colonoscopy
Double Contrast
Barium Enema (DCBE)
CT Colonography (CTC) (HS)-gFOBT/FIT Stool DNA (sDNA)

39. • Colonoscopy still GOLD STANDARD
• 20-26% miss rates for all adenomas and 2% for large
polyps.
• However results can be improved by newer techniques
such as 170-degree endoscope, 3rd
eye retroscope,
image enhancer endoscope AFI, capsule endoscopy,
narrow band imaging.
39

40. Miss rates in back-to-back studies
Heresbach et al Endoscopy 2008
Van Rijn et al Am J Gastro 2006
Kaltenbach et al Gut 2008
Iannaccone et al Radiology 2005
Year , n= All polyps Adenomas 5-
10mm
Adenomas
>10mm or
advanced
Systematic
review (6
studies)
<2004, n=465 21% 13% 2% (0.3-7.3%)
Multi-centre
study
2001-2005, n=286 28% 9% 11%
Double
colonoscopy
with CT colon
2002-2003, n=88 36% 17% 13% (6-17%)
single centre
study vs. NBI
2006-2007, n=142 13% 9.5% 0% (0-1.1%)

41. Sensitivity, Specificity,
Reliability
• Sensitivity (Sn)
– Hemoccult II < FIT ≤ Hemoccult SENSA
< FSIG < colonoscopy
• Specificity (Sp)
– Hemoccult SENSA < FIT ≈ Hemoccult II
< FSIG = colonoscopy
• Reliability
– FSIG, CTC, colonoscopy = operator-dependent (better
training/more experience improve Sn)
– quality standards/minimum volume requirements
USPSTF (2008)

42. Sensitivity, Specificity,
Reliability
• Colonoscopy has superior single-test accuracy
compared to other screening modalities
– FS+FOBT failed to identify 24% of advanced colonic
neoplasia in one study
– CTC or DCBE missed 2.1% 10+ mm polyps and miss rate as
high as 26% for smaller polyps
• Single FOBT by DRE will miss 95% of CRC
– Patients should take home 3 testing cards with 2 windows
each, use one card per day
– Cochrane review = 16% reduction in mortality (RR = 0.84,
95% CI = 0.78-0.90)
– NNS = 1,176; 10k persons completing FOBT annually will
prevent 8.5 deaths over 10 years
AFP (2008)

43. Many Available Screening Modalities
Flexible Sigmoidoscopy
(FSIG)
Colonoscopy
Double Contrast
Barium Enema (DCBE)
CT Colonography (CTC)
Detect both adenomatous
polyps and cancers.
Detect both adenomatous
polyps and cancers.

44. (HS)-gFOBT/FIT
Stool DNA (sDNA)
Detect primarily cancer.Detect primarily cancer.

45. 2008 CRC Guidelines Update:
Evidence Criteria and Limitations
• Current evidence has a number of limitations:
– Prospective studies are uncommon
– Sample sizes tend to be small
– Study participants often include higher risk, symptomatic
patients and/or screening populations (magnitude of bias
uncertain)
• Priority placed on prospective studies of asymptomatic
adults, with all subjects undergoing colonoscopy
• Because adherence to regular screening is low, we are
considering setting a test sensitivity threshold for test
acceptance

46. CRC Screening Guidelines:
What’s New?
CRC screening tests are grouped into two categories:
• Tests that detect cancer and precancerous polyps*
• Tests that primarily detect cancer
* It is the strong opinion of the consensus guidelines group
that colon cancer prevention should be the primary goal
of CRC screening.
– Exams that are designed to detect both early cancer and precancerous
polyps should be encouraged if resources are available and patients are
willing to undergo an invasive test
– If the full range of screening tests are not available, physicians should
make every effort to offer at least one test from each category

47. 2008 CRC Screening Guidelines
Beginning at age 50, both men and women at average risk for developing
colorectal cancer should use one of the screening tests below:
Tests That Detect Adenomatous Polyps and CancerTests That Detect Adenomatous Polyps and Cancer
Flexible sigmoidoscopy (FSIG) every 5 years*, or
Colonoscopy every 10 years, or
Double contrast barium enema (DCBE) every 5 years*, or
CT colonography (CTC) every 5 years*
Tests That Primarily Detect CancerTests That Primarily Detect Cancer
Annual guaiac-based fecal occult blood test (gFOBT) with high test
sensitivity for cancer *, ** or
Annual fecal immunochemical test (FIT) with high test sensitivity for
cancer*,** or
Stool DNA test (sDNA), with high sensitivity for cancer*, interval
uncertain
* Colonoscopy should be done if test results are positive.
** For gFOBT or FIT used as a screening test, the take-home multiple
sample method should be used. gFOBT or FIT done during a digital rectal exam

48. 2008 CRC Guidelines Continue
to Emphasize Options Because:
• Evidence does not yet support any single test as “best”
• Uptake of screening remains disappointingly low
• Individuals differ in their preferences for one test or
another
• Primary care physicians differ in their ability to offer,
explain, or refer patients to all options equally
• Access is uneven geographically, and in terms of test
charges and insurance coverage
• Uncertainty exists about performance of different
screening methods with regard to benefits, harms, and
costs (especially on programmatic basis)

49. Ensure Everyone Can be Offered a
Stool Blood Test Option
• Some people will not or
cannot have a
colonoscopy.
• Anyone who hesitates
should be offered a Fecal
Immunochemical Test.
• In some settings, FIT
needs to be offered as the
primary screening
strategy.

50. Stool Blood Testing Remains Important in
the “Age of Colonoscopy”
• Colonoscopy is now the most frequently used
screening test for CRC.
• However, when provided annually to average-
risk patients with appropriate follow-up, stool
occult blood testing with high-sensitivity tests
can provide similar reductions in mortality
compared to colonoscopy and some reduction
in incidence.
Evaluating Test Strategies for Colorectal Cancer Screening: A Decision Analysis for the U.S. Preventive Services Task Force

51. FOBT Sensitivity:
Take Home vs. In-Office
Sensitivity of Take Home vs. In-Office
FOBT
SensitivitySensitivity
FOBT method
(Hemoccult II)
All AdvancedAll Advanced
LesionsLesions
CancerCancer
3 card, take-
home
23.9 % 43.9 %
Single sample,
in-office 4.9 % 9.5 %
Collins et al, Annals of Int Med Jan 2005

52. In-Office FOBT should be
abandoned
Conclusion
• In-office FOBT is essentially worthless as a screening
tool for CRC and must be strongly discouraged
However;
• In a recent national survey, nearly 30% of physicians
reported using single-sample, in-office FOBT as their
primary method of screening for colorectal cancer.
Nadel et al, Annals of Int Med Jan 2005

53. Advantages of Stool Blood Testing
• Stool blood testing
• Is less expensive.
• Can be offered by any member of the health team.
• Requires no bowel preparation.
• Can be done in privacy at home.
• Does not require time off work or assistance
getting home after the procedure.
• Is non-invasive and has no risk of causing pain,
bleeding, bowel perforation, or other adverse
outcomes.
Colonoscopy is required only if stool blood testing is abnormal.

54. Stool DNA Test (sDNA)
• Rationale
• Fecal occult blood tests detect
blood in the stool – which is
intermittent and non-specific
• Colon cells are shed continuously
• Polyps and cancer cells contain
abnormal DNA
• Stool DNA tests look for abnormal
DNA from cells that are passed in
the stool*
*All positive tests should be followed with colonoscopy

55. Reasonable Cost: CRC Screening Compares
Favorably to Other Preventive
Interventions
Regardless of screening method, the cost per life-year saved
($10-25k) compares favorably with other commonly
endorsed preventive health care interventions
Pignone et al. (2002), AFP (2008)
Median cost of colonoscopy is
$1,736

56. 56

57. 57

58. Immunochemical FOB may be
better in Asia
FOB+ FIT+ SENS
FOB
SENS
FIT
SPEC
FOB
SPEC
FIT
+ predict
value FOB
+predict value
FIT
Sumetchoti
maytha et al
2007
12.6%
Hemascree
n
12.8%
Occultec
h
0.8% CRC
3.4%
polyps
1.1% CRC
8.9% polyps
Li et al 2003 35.6% 5.6% 0.2% CRC
0.6%
adenomas
Not specified
(at best
1.3% CRC
3.7% adenomas)
Wong et al
2007
41% 14% 100% 89% 70% 94% 16% CRC 42% CRC
• Cost-effectiveness: Cost of tests + false positive test
• Dietary manipulation is thought difficult in many Asian
countries

59. CT Colonography (CTC)
CTC Image Optical Colonoscopy

60. CT Colonography
Rationale
• Allows detailed evaluation of the entire colon
• A number of studies have demonstrated a high
level of sensitivity for cancer and large polyps
• Minimally invasive (rectal tube for air insufflation)
• No sedation required

61. CT Colonography
Poly
p
3-D view2-D view
Polyp

62. CTC vs. Optical Colonoscopy:
Meta-Analyses
Halligan 2005, Mulhall 2005
Polyp SizePolyp Size
CTC
performa
nce
>10mm 6-9 mm Cancer
PooledPooled
SensitivitySensitivity
85-93% 70-86% 85.7%
PooledPooled
SpecificitySpecificity
97% 86-93% ----

63. CTC vs. Optical Colonoscopy:
Sensitivities for All Polyps
Pickhardt et al, NEJM 2003
Polyp SizePolyp Size
>10mm >8mm >6mm
CTCCTC 92.2% 92.6% 85.7%
ColonoscoColonosco
pypy
88.2% 89.5% 90.0%

64. CT colonography- detection rate
• Sensitivity of CT colonography compared to 2 colonoscopies.
• 2nd
colonoscopy aware of all lesions detected from CT and initial
colonoscopy
• Minimised known miss rate- true sensitivity of CT results
All polyps
>6mm
Neoplastic
>6mm
Neoplastic
>10mm (n=7)
All polyps All
neoplastic
Second
colonoscopy
100% 100% 100% 100% 100%
Initial
colonoscopy
84%
(69-92%)
91%
(71-97%)
86%
(49-97%)
83%
(74-89%)
87%
(73-94%)
CT colon
(3 observers)
86%
(72-94%)
81%
(60-92%)
100%
(70-100%)
63%
(53-72%)
64%
(48-77%)
Iannaccone et al 2005

65. The ACRIN CT Study
• The ACRIN study is a multi-center study with each
site using state-of-the-art technology
• 15 participating sites
• Patients underwent both CTC and colonoscopy
• 2,531 asymptomatic patients studied
• Findings published Sept 2008 in New England Journal

66. ACRIN Results
SensitivitySensitivity SpecificitySpecificity
Adenomas > 1
cm 90% 86%
Polyps 6-9
mm 84% 86-89%
Johnson et al, NEJM 2008

67. CT Colonography
Limitations
• Requires full bowel prep (which most patients find to be the
most distressing element of colonoscopy)
• Colonoscopy is required if abnormalities detected, sometimes
necessitating a second bowel prep
• Steep learning curve for radiologists
• Limited availability to high quality exams in many parts of the
country
• Most insurers do not currently cover CTC as a screening modality

68. Limitations
• Extra-colonic findings can lead to additional
testing
(may have both positive and negative
connotations)
• Questions regarding:
 Significance of radiation exposure
 Management of small polyps

69. Risks of Screening
• Bowel Perforation
– CTC = 0-6 per 10,000
– DCBE = 1 per 25,000
– FSIG = 1 per 25,000-50,000
– Colonoscopy = 1 per 2,000-3,000 (65% are sigmoid)
• Serious Complications
– death or event requiring hospitalization (perforation,
major bleeding, diverticulitis, severe abdominal pain,
and cardiovascular events)
– FSIG = 3.4 per 10,000 procedures
– Colonoscopy = 25 per 10,000 procedures

70. Risks of Screening
• Conscious Sedation
– FSIG = most performed without (some discomfort)
– Colonoscopy = most performed with
(cardiopulmonary complications are ~½ of all adverse
events); patients will also miss a day of work and need
a chaperone for transportation
• Bowel Prep
– FSIG = less intensive (complete or partial)
– Colonoscopy = more intensive (complete required)
– DCBE/CTC* = complete required, if same day
colonoscopy not available a second bowel prep will be
required

71. Risks of Screening
• False Reassurance from False-Negative Results
(gFOBT/FIT)
• Unnecessary Invasive Tests Due to False-
Positive Results (CTC)
– 10% of first-time CT colonographies found to have
extracolonic abnormalities which may or may not
be clinically significant; potential for both benefit
& harm

72. Risks of Screening
• Radiation Exposure (CTC)
– radiation exposure reported to be 10 mSv per CTC
– at this level of exposure, 1 additional individual per
1000 would develop cancer in his or her lifetime
– cumulative radiation risk should be considered in the
context of the growing use of other diagnostic and
screening tests that involve radiation exposure.
– improvements in CT colonography technology and
practice are lowering this radiation dose

73. Flat Lesions
• Described in Japanese patients since 1980’s. Thought to
be uncommon in the U.S.
• Study published in March 2008 detected flat lesions at
much higher rate than any previous U.S. reports
• Colonoscopies in over 1800 veterans found:
– Polyps in 37%
– “Flat lesions” in 9.35%
– 0.8% of flat lesions cancerous or pre-cancerous
Soetikno, JAMA 2008

74. Flat Lesions
Caveats
• Most lesions
not truly flat
– Flat lesions
found in only 6%
– Cancer or pre-
cancerous
findings in only
0.3%
Soetikno, JAMA 2008
New Sources of Risk
Colorectal cancer prevention largely focuses
on finding polyps, but flatter, less visible lesions
that are not polyps are also cancer risks.
Polyp
Elevated
lesion
Flat
lesion
Depressed
lesion
The New York Times: Illustrations by JAMA

75. Flat Lesions
Implications for screening
• JAMA study led some to question the ability of CTC to
detect flat lesions (although CTC was not utilized in the
study)
• Results from early CTC/flat lesion studies were
extremely variable (sensitivity 13% - 65%)
• Recent study of experienced radiologist using advanced
technology and protocols found 80% sensitivity for flat
lesions

76. Thank youThank you