CTC Status and Possible Future Developments D l t Arnold C. Friedman M.D. FACR
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.
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
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.
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
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
Indications1. Screening for colorectal cancer and polyps in asymptomatic, average-risk average risk patients aged ≥50 years2. Surveillance in patients s/p resection of CRC (add-on to CTAP) or with known unresected colorectal polyps3. 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 mm4. Diagnostic testing in symptomatic patients, in the appropriate clinical context5.5 Complete full structural examination of colorectum after incomplete endoscopy6. 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
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
Contraindications1. 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 SBO2.2 Routine follow up of inflammatory bowel follow-up disease3. Screening of high-risk patients (e.g., hereditary polyposis or nonpolyposis cancer syndromes) l i l i d )4. Evaluation of anal canal disease5.5 Pregnancy
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.
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?
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.
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.
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.
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.
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
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
5 mm cecal polyp missed by me but detected byCAD
5 mm cecal polyp missed by me but detected byCAD
Prone false positive CAD mark in the sigmoid onthe axial (yellow circle) due to barium tagged stool.On endoluminal 3D it looks just like a small polyp.
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.
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.
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.
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.
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
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.
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
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………….
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