1. CTC Status and Possible Future
Developments
D l t
Arnold C. Friedman M.D. FACR

2. Validation Status
• Between the birth of CTC in the mid-1990’s and 2003 clinical trial
results were poor but lacked MDCT 3D detection and fecal tagging
MDCT, tagging.
• A 2003 DoD trial reported 92% sensitivity for polyps >10 mm and a
per patient sensitivity for polyps >6 mm of 89%, not significantly
different from that of OC.
• 2007 UW CRC screening program- similar CTC and OC detection
rates for advanced adenomas and carcinomas. The CTC arm had
fewer polypectomies (561 vs. 2434) and no perforations vs. 7
p
perforations in the OC arm.
• 2008 ACRIN trial- sensitivity of 90% for advanced adenomas or
carcinomas >10 mm. Several other large screening trials in the US
(Mayo Clinic) and Europe (Germany, Italy) have reported similar
results.
results
• 2008-2009 U of AZ telemedicine trial- screening CTC performed in a
rural setting and interpreted remotely with good results.

3. Reimbursement Status
• 2008: ACS and the US Multi-Society Task Force on CRC endorsed CTC for
CRC screening USPSTF gave CTC an indeterminate status based on
screening.
concerns about radiation and extracolonic findings. CMS has no national
coverage determination for diagnostic CTC, but 47 states have local
coverage determinations, mainly limited to incomplete OC and high-risk.
• 2009: CMS released a noncoverage decision for screening CTC with
concerns being lack of data in Medicare populations (unsubstantiated in two
recent studies), cost-effectiveness, extracolonic findings, and radiation.
• Private payer coverage for screening CTC has been increasing.
– Screening CTC covered in Wisconsin since 2004.
– The BCBS Technology Evaluation Center released a positive assessment in
09/08 leading to positive coverage decisions by Anthem, Wellmark, Empire and
Horizon for screening CTC.
– Kaiser Permanente passed a positive technology assessment supporting CTC
for screening.
screening
– Cigna and United Healthcare have made positive screening decisions in some
regions.
• Active Duty, VA

4. Legislative Action
• 19 state legislatures and DC have passed
laws requiring private insurance carriers to
reimburse for CRC screening procedures
procedures,
with most of them specifically mandating
CTC or any modality endorsed by ACS ACS.
• Similar legislation is being considered in
other states and in Congress
Congress.

5. The Top Twenty
Alabama
Alaska
Arkansas
Connecticut
Delaware
District of Columbia
Georgia
Illinois
Indiana
Louisiana
Maine
Maryland
Missouri
Nevada
New Jersey y
North Carolina
Rhode Island
Tennessee
Texas
Virginia

6. CPT Codes and RVU’s
RVU s
• 2004: Initial nonreimbursable tracking CPT
codes for CTC- 0066T for screening and
0067T for diagnostic.
diagnostic
• Effective 1/1/10: 74263 screening CTC
w/o contrast 74261 diagnostic CTC w/o
contrast,
contrast, and 74262 diagnostic CTC
w/contrast.
w/contrast
Undervalued, CT Abd w/o is 1.2 RVU

7. Indications
1. Screening for colorectal cancer and polyps in asymptomatic,
average-risk
average risk patients aged ≥50 years
2. Surveillance in patients s/p resection of CRC (add-on to CTAP) or
with known unresected colorectal polyps
3. CTC offered along with OC as a p
g patient choice for follow-up of a
p
screening CTC showing 1-2 polyps between 6 and 9 mm
4. Diagnostic testing in symptomatic patients, in the appropriate
clinical context
5.
5 Complete full structural examination of colorectum after
incomplete endoscopy
6. Patients at increased risk for OC (anticoagulation or other
bleeding diathesis, sedation risk, previous incomplete OC)
7. Characterization of indeterminate colorectal lesions found on
colonoscopy

8. CTC for Incomplete OC
• CTC can be performed the same day after an
incomplete OC t obviate another b
i l t to b i t th bowel prep or a
l
more taxing DBCE.
• In patients with incomplete OC due to occlusive
lesions CTC can id tif proximal synchronous l i
l i identify i l h lesions
that might otherwise be missed. IV contrast can be
used to stage the occlusive lesion.
• One can consider a low dose thick slice CTAP prior to
the CTC to identify any free air that would be a marker
of an asymptomatic perforation occurring during the
preceding OCOC.
• Although barium fecal tagging is not feasible iodine
fluid tagging should be performed with oral iodinated
contrast 2-3 hours prior to the CTC for incomplete OC.
23

9. Contraindications
1. Caution is indicated in patients with acute
p
colitis, acute diverticulitis, recent colorectal
surgery, symptomatic colon-containing hernia,
recent endoscopic biopsy, p yp
p p y, polypectomy, or
y,
mucosectomy, suspected perforation, and
high-grade SBO
2.
2 Routine follow up of inflammatory bowel
follow-up
disease
3. Screening of high-risk patients (e.g., hereditary
polyposis or nonpolyposis cancer syndromes)
l i l i d )
4. Evaluation of anal canal disease
5.
5 Pregnancy

10. Bowel Preparation
• Saline cathartics: sodium phosphate and mag
p p g
citrate.
• Lavage: formulations of polyethylene glycol.
• Warnings against the use of sodium phosphate
in the elderly, in pts with impaired renal function
or in pts on ACE inhibitors have discouraged its
use ddespite only needing a single d
it l di i l dose f CTC
for CTC.
Mag citrate is still used.
• PEG is safer but less pleasant than saline
G s sa e ess p easa t t a sa e
cathartics and results in much more fluid in the
colon. This can be ameliorated with iodine fluid
tagging.
tagging Movement is towards PEG products
products.

11. Cathartic less
Cathartic-less Prep
• The holy grail of CTC since the catharsis is by far the
yg y
most unpleasant part of the exam.
• Combinations of low-residue diets, specially designed
foods, barium tagging and/or and lots of hypertonic oral
iodine and 2D interpretation.
• Some acceptable results but no real validation. One
problem is that primary 3D reading is not possible
possible.
• Software electronic cleansing might permit 3D reading,
but currently it is hampered by artifacts.
• Dual source CT for electronic cleansing? IV contrast or
PET-CT to differentiate polyps from stool?

12. Unsuccessful Electronic Cleansing

13. Successful Electronic Cleansing

14. Successful Electronic Cleansing

15. Stool and Fluid Tagging
• Barium is ingested with meals the day before the
g y
exam and iodinated contrast the night before the
exam.
• B i
Barium tags stool b
l better than d
h does i di and
iodine d
iodine tags fluid better than barium does.
• Since polyps and cancers enhance and stool
enhance,
does not, IV contrast can aid in their detection.
However, its use is restricted to staging known
CRC by CTC or the occasional diagnostic
dilemma.

16. Colonic Distention
• Can be achieved with automated
insufflation of CO2 (used by most, maybe
we can even get credit one day for
g y
reducing greenhouse gases?) or manual
insufflation of room air. Spasmolytics are
not routinely used.
t ti l d
• Conversion to manual insufflation should
take l
t k place if automated insufflation is
t t di ffl ti i
suboptimal.

18. Dose Reduction
• Can be achieved with automatic exposure
control or technique charts or by arbitrarily
using 50 mAs supine and 25 mAs prone
prone.
• Screening CTC dose about 1/3-1/2 that of
routine abdomen and pelvis CT and on the
order of the yearly background radiation.
• I the morbidly obese hi h d
In th bidl b higher doses are
needed.

19. Interpretation
• 2D transverse images, MPR’s and 3D endoluminal display are the
principal tools for interpretation
interpretation.
• A primary 3D approach is more sensitive for small polyps but more
time-consuming. Both sides of folds must be examined, requiring
both antegrade and retrograde flythroughs in each position. Risk of
blind
bli d spots, b t small especially with 1200 camera angle.
t but ll i ll ith l
• Polyp candidates are problem solved on 2D to examine tissue
texture and density and mobility on supine vs. prone position.
• With a primary 2D approach polyp candidates must still be assessed
on 3D for morphology. The interpreter must be facile with both
approaches. 2D is used when pts are not well cleansed. No blind
spots.
• Novel 3D displays for faster 3D interpretation exist but are not fully
validated and some have disadvantages such as distortion.

20. Conventional Camera

21. Novel Views
• Eliminate Blind Spots
• Permit Unidirectional Flythroughs, save
time
• Potential cuts in interp time substantial
e.g. f
from 14.6 ± 2 5 mins t 7 5 ± 3 2 mins
14 6 2.5 i to 7.5 3.2 i
b/c unidirectional flythrough shows entire
mucosal surface.
l f

22. Virtual Dissection

23. Virtual Dissection

25. Unfolded Cube Projection

26. No Distortion
8.5 mm polyp

27. Computer-Aided Detection (CAD)
most recent paper
• The Good: Reader assessment changed from
FN to TP in 14% of pts and from TP to FN in 8%
of pts with CAD compared to no CAD. The
estimated net gain in TP’s was 6%.
– Sensitivity up
• The Bad: Reader assessment changed from FP
to TN in 6% of pts and from TN to FP in 10.0%
of pts with the use of CAD The net effect was
CAD.
an increase of 4% in FP’s.
– Specificity down

28. 5 mm cecal polyp missed by me but detected by
CAD

29. 5 mm cecal polyp missed by me but detected by
CAD

30. Prone false positive CAD mark in the sigmoid on
the axial (yellow circle) due to barium tagged stool.
On endoluminal 3D it looks just like a small polyp.

31. Computer Aided
Computer-Aided Detection (CAD)
• Current CAD systems lack sufficient sensitivity
y y
to be used as a first reader.
• Most recommend using CAD as a second reader
because of the danger of a false sense of
security if it is used as a concurrent reader.
• As a second reader it may increase sensitivity
for
f small polyps b t th
ll l but there will b d
ill be decreased
d
specificity and an increase in interpretation time
(~4.5 min).
• Likely not to be successful commercially until
reimbursable separately- see CAD for mammo.

32. Risks and Limitations of CTC
• Screening CTC is to filter pts to therapeutic OC. Using a size threshold of
>6 mm the OC referral rate in a screening cohort should be about 8% 8%.
Given the need for high sensitivity there will be FP’s (?20-40%).
• Flat lesions are harder to detect on CTC than polypoid lesions. The same is
true for OC. Debate about the prevalence and significance of flat lesions in
the US screening population is ongoing Depending on the definition of flat
ongoing.
lesion, its detection rate on CTC when >10 mm may be on the order of 70-
80%.
• Currently a cathartic bowel preparation and a restricted diet are used for
CTC which negatively impacts p
g y p patient acceptance. However, it p
p , permits
same-day OC polypectomy without additional preparation if this is feasible
for the local gastroenterologist.
• Risks of CTC
– Bowel preparation (
p p (similar to OC),
)
– Colonic insufflation: perforation during screening CTC is “virtually” unheard of.
– Ionizing radiation: A study of pilots receiving mean annual doses of 2-5 mSv
(similar to one screening CTC annually) failed to show any increased cancer
mortality.

33. CTC Target Lesion Definition
• The advanced adenoma, defined as tubular adenoma >10mm,
adenoma with high grade dysplasia or significant villous
high-grade
components, or invasive cancer, is the target for removal for CRC
prevention. Obviously polyp size and morphology but not histology
are depicted by CTC.
• Rates f d
R t of advanced adenoma i specific size categories are reported
d d in ifi i t i t d
as 3.4-5.4% in 6-9 mm polyps and 0.9-1.2% in polyps <5 mm.
• The rate of malignancy in polyps <5 mm is estimated at 0.05%.
• Longitudinal studies suggest indolent behavior for most small
polyps. Some may even regress.
• It is estimated that 5.5 years is required on average for the
transformation of a >10 mm adenomatous polyp into a carcinoma.
• Given the small chance of advanced adenoma and th hi h FP rate
Gi th ll h f d d d d the high t
for diminutive polyps on CTC, and the possibility of postpolypectomy
bleeding it seems more cost effective not to report diminutive <5 mm
polyps in screening CTC patients.

34. CTC Extracolonic Findings
• In two recent CTC screening series further diagnostic workup for
unsuspected ECF’s was performed in 6% and 4% Benign findings
ECF s 4%.
were confirmed in the majority of cases, but relevant new diagnoses
were made in 2.5% of pts. The average cost of work-up per patient
screened was ~$39 (in a study with an E3 likely benign ECF rate of
9.3%).
9 3%) CMS cited an ECF w/u rate of 16% 16%.
• Good judgment in ECF reporting is necessary to provide maximal
exam benefit and minimize the anxiety and cost of unnecessary
follow-up imaging or other diagnostic/therapeutic procedures.
• I discourage pursuit of too small to characterize liver, renal and
adrenal lesions that are almost certainly benign in a screening
population. If you are uncomfortable with this don’t read CTC’s.
• ECF s
ECF’s are a good thing- 0 35% rate of extracolonic malignancy in a
thing 0.35%
screening population (mostly RCC, lung ca and NHL) compared to
0.21% CRC.

35. Cost Effectiveness
Cost-Effectiveness of CTC
• Studies in the GI literature nearly always have shown that CTC was
cost effective compared to no screening (important for those
patients unwilling to undergo OC) but inferior to OC. Factors limiting
accuracy of these findings include: outdated sensitivity values for
CTC, overly optimistic values for OC, inaccurate cost estimates
(ignoring missed work due to sedation) and ignoring improved
patient compliance with CTC.
• A recent study in the radiology literature compared CTC, OC and
flexible sigmoidoscopy and found that CTC with a reporting
threshold f
th h ld of 6 mm was th safest and most cost effective screening
the f t d t t ff ti i
option.
• Arch Intern Med: The consequences of ECF’s have been difficult to
assess but have generally been assumed to lead to useless
g y
additional cost. However, when the benefits of discovering important
extracolonic findings such as AAA and unsuspected cancers are
included, screening CTC is more cost effective than OC even if
sonography for AAA is added to OC.
g p y

36. Cost Effectiveness
Cost-Effectiveness of CTC
• A recent JNCI article focused on the Medicare population (ignored
ECF and used 5 yr screening interval for CTC compared to 10 yr for
OC).
– Undiscounted number life-years gained from CTC screening
ranged from 143 to 178 per 1000 pts
– Comparable to 10-yearly OC (152–185 per 1000) and 5-yearly
sigmoidoscopy with annual FOBT (149–177 per 1000 pts)
• If CTC screening was reimbursed at $488 per scan (slightly less
than the reimbursement for a colonoscopy without polypectomy) it
polypectomy),
would be the most costly strategy.
• CTC screening could be cost-effective at $108–$205 per scan.
• If relative adherence to CTC screening was 25% higher than
adherence t other t t it could b cost-effective if reimbursed at
dh to th tests, ld be t ff ti i b d t
$488 per scan.

37. CTC Training and Certification
• Education in pt preparation, bowel inflation, and image acquisition.
• For i i i l i i
F initial training, iinterpreting physicians should perform h d
i h i i h ld f hands-on
primary 2-D or primary 3-D search for colorectal lesions in 50 (if
skilled in abdominopelvic CT) or 75 (if unskilled in CT)
endoscopically confirmed cases.
• Cases should display the gamut of morphologic appearances of
colorectal neoplasia and pseudolesions with different preps.
• Group review of CTC cases without individual experience with CTC
interpretation is insufficient for training
training.
• Ideally mentored supervision or double reading is initially performed.
• For maintenance of competence, 50 CTC cases should be reviewed
every 2 years including endoscopically confirmed cases in individual
practice and CME activity with i t
ti d ti it ith interpretation preceding unblinding.
t ti di bli di

38. ACR CTC Quality Metrics
• Appropriate indication
• Appropriate CT technical parameters
A i h i l
• Percentage of completely diagnostic exams
• Complication rate
• Significant extracolonic finding rate
• Endoscopic referral rate
• TP/FP rates for exams with OC follow-up
• The ACR has a National Radiology Data Registry into which these
data can be entered
• MQSA for CTC coming? Probably………….

39. References
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y g p y g
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6.
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AC, D, al.
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40. References
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