Curr Gastroenterol Rep (2011) 13:486–494 DOI 10.1007/s11894-011-0217-5

Evidence Review and Status Update on Computed Tomography Colonography Darren Boone & Steve Halligan & Stuart A. Taylor

Published online: 20 July 2011 # Springer Science+Business Media, LLC 2011

Abstract Computed tomographic (CT) colonography is being implemented increasingly in the USA and Europe, and in many centers it has become the radiological technique of choice for imaging the whole colorectum. Although high diagnostic accuracy has been demonstrated in both screening and symptomatic populations, controversy persists regarding implementation, who should interpret the examination, and its cost effectiveness, particularly in the context of primary colorectal cancer screening. Published research in recent years has demonstrated efficacy in a wide range of patient groups, striking technical improvements, and high levels of patient acceptability. New developments continue in the fields of computer aided detection, digital cleansing, and integration into positron emission tomography. The purpose of this review is to bring the reader up-to-date with the latest developments in CT colonography, in particular, those of the last year. Keywords CT colonography . CTC . Virtual colonoscopy . Colorectal cancer . Neoplasia . Polyp . Adenoma . Performance . Accuracy . Sensitivity . Specificity . Diminutive . Flat . Barium enema . Colonoscopy . Cost effectiveness . Computer-aided-detection . CAD . Training . Standards . Validation . Acceptability . Bowel preparation . Safety . Extra-colonic findings D. Boone : S. Halligan : S. A. Taylor Centre for Medical Imaging, University College Hospital, 250 Euston Road, London NW1 2BU, UK S. A. Taylor (*) Centre for Medical Imaging, University College Hospital, Podium Level 2, 235 Euston Road, London NW1 2BU, UK e-mail: [email protected]

Introduction CT colonography (CTC) involves helical CT scanning of the cleansed, distended colorectum followed by three-dimensional image rendering to simulate the endoscopic view, hence the alternative title “virtual colonoscopy.” Within-subject comparisons between CTC and conventional colonoscopy have reported similar detection rates for polyps 10 mm or larger [1•• 2, 3], and meta-analysis data supports good diagnostic performance [4]. Moreover, it is now established that CTC is more accurate and acceptable to patients than its radiological alternative, the barium enema [5••]. In recent years however, increasing controversy has surrounded the implementation of CTC into daily practice, particularly in the context of colorectal cancer (CRC) screening—not least due to conflicting recommendations by national groups in the US [6, 7]. Cost-effectiveness models yield divergent results contingent upon baseline assumptions such as improved uptake within CRC screening programs [8] and the impact of incidental extra-colonic findings [9•]. Furthermore, the debate as to who should interpret CTC (radiologists, gastroenterologists, radiographic technicians, or even computer algorithms) continues to intensify. Even 17 years after its first description, CTC remains the focus of considerable research interest around the globe with over 200 peer reviewed publications in the last year alone. In this article, we review the recent, indexed research in this field and focus in particular on diagnostic efficacy, technical implementation, patient acceptance and future directions.

Diagnostic Performance Excellent diagnostic accuracy has been reported in several large comparative studies, mainly performed in average-risk

Curr Gastroenterol Rep (2011) 13:486–494

487

screening populations (Table 1). Three significant additions to the literature have recently originated from Europe: The UK Special Interest Group in Gastrointestinal and Abdominal Radiology (SIGGAR) study [5••], the Italian Multicentre Polyps Accuracy CTC (IMPACT) trial [10••], and the Munich colorectal cancer prevention study [11••] assessed CTC performance in symptomatic, high risk and average risk populations respectively. Diagnostic Performance in Symptomatic Patients Investigating symptomatic patients predominates in European CTC research and abstracted data from the SIGGAR study [5••] should quell any remaining debate regarding the preferred radiologic examination in this setting. This multicenter study led by Steve Halligan and Wendy Atkin [12] comprised two parallel randomized controlled trials (RCT) comparing CTC to barium enema and CTC to optical colonoscopy; a total of 5448 patients were randomized. The primary end point was the detection rate for colorectal cancer or polyps ≥1 cm in symptomatic adults. In the barium enema RCT, patients aged 55 or over with symptoms suggestive of colorectal cancer who were referred by their clinician for barium enema were randomized (in a 2:1 ratio) to either barium enema (2541) or CT colonography (1280). In an intent-to-treat analysis, colorectal cancer or polyps ≥10 mm were diagnosed significantly more frequently in patients assigned to CTC than to barium enema (7.4% vs. 5.6% , P=0.0312). Using national registry data to capture cancer miss rates (diagnosed within 2-years of randomization), barium enema had twice the miss rate of CTC (14% vs 7%). Additional colonic investigations occurred significantly more frequently following CTC than BE (23% vs. 18%), mainly due to higher polyp detection rates. A total of 1338 previously unknown extra-colonic findings were reported in the 1206 patients who underwent CTC as their randomized procedure. A total of 86 patients were referred for further tests as a result of their extra-colonic Table 1 Diagnostic performance of CT colonography compared to same-day, un-blinded colonoscopy; comparison of three recent trials

*Graser et al. [11] employed thresholds of >5 and >9 mm, respectively

Number of patients in analysis risk of neoplasia Mean age (years) Per patient sensitivity • Adenoma ≥6 mm* • Adenoma ≥10 mm* • Cancer Per patient specificity • Adenoma ≥6 mm* • Adenoma ≥10 mm*

findings, leading to diagnosis of a malignant tumor in 12 patients [13•]. As a result of these data, the UK Department of Health has deleted barium enema from its faecal occult blood test (FOBT) based national screening program for colorectal cancer and recommends CTC in its place. The colonoscopy RCT [12] found a much higher prevalence of endpoints amongst those randomized (11% vs 4% for the enema trial). In an intent to treat analysis, there was no significant difference in the detection rate of significant colorectal neoplasia between the two arms (11.6% for colonoscopy vs 10.7% for CTC, P=0.61) but the referral rate for a subsequent confirmatory procedure was much higher after CTC (31.4% for CTC vs 7.2% for colonoscopy), raising important questions about costs and the need for well-defined criteria for subsequent referral following CTC in symptomatic patients. Diagnostic Performance in Asymptomatic Patients The IMPACT and Munich trials performed prospective studies comparing CTC against the enhanced reference standard of un-blinded, same-day colonoscopy: The IMPACT study [10••] recruited patients at increased risk of colonic neoplasia such as those with a personal history of adenomatous polyps, a family history of advanced neoplasia or a positive faecal occult blood test (FOBT). Overall, 1103 patients were recruited from 11 sites in Italy and one in Belgium. CTC detected 151 of 177 participants with advanced neoplasia (≥ 6 mm) resulting in a sensitivity of 85% (95% CI, 79–90%) and a specificity of 88%; (95% CI, 85–90%). Considering larger polyps (≥10 mm), CTC had sensitivity of 91% (95% CI, 84–95%) with positive and negative predictive values of 62% and 96%, respectively. Subgroup analysis of the FOBT-positive group found a significantly lower negative predictive value (85%; 95% CI, 76–91%; P<0.001) which is of concern given the high prevalence of important colonic abnormalities in these patients. This concern was also highlighted by a separate

Johnson et al., 2008 [1]

Regge et al., 2009 [10]

Graser et al., 2009 [11]

2531

937

307

Predominantly average risk (89%) 58

All considered at increased risk (see text) 60

All considered average risk 61

78% 90% 86%

85% 91% 95%

91% 92% 100%

88% 86%

88% 85%

93% 98%

488

Italian study [14] which specifically compared CTC performance in 49 FOBT-positive patients against same-day colonoscopy and found disappointing results. Polyps of 6 mm or larger were present in 45% of patients and although a high per-patient sensitivity (96%) was achieved, specificity and positive predictive value were low at 52% and 62%, respectively. The authors of that study suggested poor specificity was due to the lack of oral faecal tagging in the study protocol. Overall, it seems the use of CTC for primary triage of patients with positive FOBT is unlikely to be cost effective. This may change with the introduction of immunological FOBT, which has higher sensitivity but lower specificity than currently available tests. The Munich Colorectal Cancer Prevention Trial [11••] examined asymptomatic patients with an average colorectal cancer risk. A total of 307 patients with 511 endoscopically detected adenomas underwent five different screening tests in parallel: CTC, colonoscopy, flexible sigmoidoscopy, guaiac-based FOBT and immunochemical stool tests. Akin to the IMPACT study, performance was compared to sameday colonoscopy as the reference standard. CTC detected 94% of adenomas larger than 9 mm and although sensitivity for sub-centimetre adenomas (including those less than 5 mm) was lower at 66%, only one missed adenoma showed advanced histology, enabling the authors to report a sensitivity of 93.5% for “advanced neoplasia.” Encouragingly, per-patient specificity for polyps larger than 5 mm was 93%. Diminutive Lesions Few authors, if any, would disagree that the sensitivity and specificity of CTC is relatively poor for diminutive polyps and the focus has therefore been on detecting polyps larger than 5 mm, ideally those with high grade dysplasia (ie advanced adenomas). The ability of CTC to detect important colonic lesions was provided by Benson et al. [15], who compared 1700 average-risk screening patients undergoing colonoscopy and 1307 having CTC. No significant difference between the two techniques was found for detection of advanced adenomas, but nearly five times more non-advanced adenomas were removed in the colonoscopy group. While much is known about the natural history of colorectal cancer, it remains unclear whether detection and excision of small adenomas is clinically desirable. For example, a meta-analysis of four studies comprising 20,562 screening patients by Hassan et al. [16•] found that advanced adenomas were detected in 1155 (5.6%) subjects, with an overall incidence in polyps <6 mm, 6–9 mm and ≥10 mm of 4.6%, 7.9% and 87.5%, respectively. They concluded that a 10 mm polyp size threshold for colonoscopy referral would identify 88% of advanced neoplasia

Curr Gastroenterol Rep (2011) 13:486–494

while a 6 mm threshold would identify over 95%. Additional complexity results from the well documented systematic differences in polyp measurement between radiological and endoscopic techniques. De Vries et al. [17] assessed endoscopic and colonographic measurement of 51 polyps and found CTC judged polyps to be between 0.7 to 2.3 mm larger than equivalent endoscopic estimates. Debate also continues as to how endoscopic and colonographic definitions of flat neoplasia can be reconciled to allow meaningful comparisons. Ignjatovic et al. [18] performed a comprehensive review of the subject, and suggested the most appropriate radiological definition for CTC should be based upon the well established pathological description (Paris classification); ie, a lesion with a vertical height of 3 mm or less above the surrounding mucosa. In support, a single centre study of 5107 consecutive CTC screening patients harbouring 125 lesions characterised as flat at endoscopy found 93% of would lie within the proposed 3 mm threshold [19]. Interestingly, the study also noted that flat lesions between 6 and 30 mm in size were less likely to be neoplastic than similar sized sessile polyps (25% vs 60%). Cost Effectiveness of CTC for Primary Screening Although CTC has proven effective for advanced adenoma detection, whether it represents a cost-effective primary screening tool remains debated due to uncertainties in baseline assumptions, notably the impact of extra-colonic findings, management of diminutive polyps, potential to increase patient compliance with colorectal cancer screening, and reimbursement rates. Conflicting recommendations have been given by two North American consensus guideline groups. In a joint statement by the American Cancer Society, the Multi-Society Task Force on Colorectal Cancer and the American College of Radiology, CTC was recommended as a first-line preventive screening test in patients at average risk of developing colorectal cancer [7]. However, the US Preventive Services Task Force considered the existing evidence insufficient [6] and CTC has been rejected for coverage by the Centers for Medicare and Medicaid Services [20]. A recent analysis by Knudsen et al. [8] concluded that a substantial increase in screening attendance (>25%) would be required for CTC to be cost effective in comparison to colonoscopy. In response, Pickhardt et al. [21] argued that implementation of CTC screening would indeed comfortably increase compliance, notably among patients who currently refuse colonoscopic screening. They cite a survey by Moawad et al. [22], which found 40% of patients attending colonography screening would have foregone investigation altogether had CTC not been available and a survey of colonoscopy non-attendees, of whom over 80%

Curr Gastroenterol Rep (2011) 13:486–494

stated that they would have attended CTC instead [23]. Some caution must be applied to both surveys. The first study was prone to selection bias as all respondents had already chosen to attend CTC, and the second had a response rate of only 39%, raising concerns about the generalizability of their results. Nevertheless, the potential for CTC to enhance screening adherence is a tantalising prospect, and prospective research that determines true compliance rates within a national screening program are eagerly awaited. In terms of extra-colonic findings, recent modelling suggests the high sensitivity of CTC for detecting aortic aneurysms will increase its cost effectiveness compared to the current screening strategy of colonoscopy and ultrasound [24•]. Although these developments primarily concern North American practice, their impact on CTC implementation and future research has international implications. While full discussion of the debate is outside the scope of this review, interested readers are recommended excellent commentaries by Cash, [25] Schoen, [26] and Burke [27].

Training, Standards, and Validation A consistent theme in the CTC literature, even among the larger successful studies, has been notable variation in diagnostic accuracy for individual radiologists. It is therefore surprising that research in recent years has contributed relatively little to our understanding of the effects of reader experience and training on interpretative accuracy. Fletcher et al. [28•] compared the performance of ten radiologists during a one-day educational workshop with their subsequent diagnostic accuracy in a prospective multicenter screening study and found a 1.5-fold increase in the odds of making a true positive diagnosis for every 50 validated cases studied. However, a recent survey of attendees at European Society of Gastrointestinal and Abdominal Radiology (ESGAR) CTC courses [29•] showed that 76% of respondents actively interpreting CTC in their daily practice had personal experience of fewer than 50 cases. Subsequently, a new CTC standards document developed by the International CT Colonography Standards Collaboration [30•] has reinforced the need for adequate training and has suggested validation of competency by formal testing. Likewise, the American College of Radiology has recently recommended quality metrics [31••] including rates of complications, inadequate studies and significant extracolonic findings. Where patients undergo subsequent colonoscopy they advise registering sensitivity and specificity for polyps ≥1 cm. The aim is to establish benchmarks against which departments can audit their performance.

489

Bowel Preparation and Patient Acceptability Quantitative assessments of patient experiences and attitudes have shown that CTC is often preferred to colonoscopy, and this underpins the assumption that its introduction will increase compliance with CRC screening programs. For example, a questionnaire survey of 250 consecutive asymptomatic average-risk patients [22] found that had CTC not been available, 91 patients (36%) would have foregone screening. The most common reasons for choosing CTC over colonoscopy were stated as convenience (33.6%), clinician recommendation (13.2%), and perceived safety (10.8%). Furthermore, of 57 patients who had experienced both procedures, 95% preferred CTC. Nevertheless, patient preference for CTC is by no means universal or consistent in the indexed literature. Qualitative data have shown that patients particularly dislike the required cathartic preparation [32]. Such observations have stimulated ongoing interest in reduced laxative regimens incorporating oral fecal tagging agents prior to CTC. A consecutive series of 173 patients at increased risk of colorectal cancer who underwent both colonoscopy and limited preparation CTC (180 mL diatrizoate meglumine, 80 mL barium, and 30 mg bisacodyl) [33] found participants experienced significantly more pain and discomfort during colonoscopy than during CTC (p<0.001). While reducing the laxative burden undoubtedly improves patient opinions of CTC, when interviewed directly, it is clear they still prioritize diagnostic accuracy over test comfort, and this may influence whether they ultimately decide to undergo colonoscopy instead [32]. It is essential, therefore, that reduced preparation techniques maintain comparable sensitivity to full laxative preparations. Mahgerefteh et al. [34•] systematically reviewed nine studies that prospectively compared the diagnostic accuracy of decreased-laxative CTC with colonoscopy. The authors concluded that although good diagnostic performance can be attained, data are currently relatively limited and study designs are inconsistent. While iodinated contrast based regimens are increasingly favored over barium based preparations, it should be remembered that the former may cause significant diarrhea if used in high doses. A wide range of reduced bowel preparation regimens are currently being investigated (which differ markedly in oral contrast type, dose, and timing of administration). Indeed, the heterogeneity of tested regimens currently precludes meaningful metaanalysis of reduced laxative CTC. Research regarding different regimens continues apace and the results of ongoing large prospective studies are expected in the near future.

490

Safety While it is widely accepted that CTC is safe with a perforation rate considerably lower than that of colonoscopy, risks do exist, and knowledge of these risks continues to inform best practice. A meta-analysis by Atalla et al. [35•], supplemented by a retrospective multicentre study identified only two cases of perforation from 3458 studies resulting in an incidence of 0.06%. Risk factors common to both cases were older age, manual colonic insufflation, diverticulosis, recent colonoscopy, and biopsy. The potential relationship to prior colonoscopic biopsy is of interest, but given the low rates of CTC related perforations in the literature, there remains insufficient evidence on which to base clear guidelines for the timing of CTC following endoscopic biopsy. This issue however will likely become of increasing importance, as many institutions attempt to offer same-day CTC following incomplete colonoscopy. Recently, CTC has been shown to be safe following metallic stent placement for obstructive colorectal cancer [36]. It is well known that aggressive bowel purgation carries a risk of biochemical disturbances, particularly in frail elderly patients. However, a retrospective study of patients aged over 70 years demonstrated no significant changes in serum urea, sodium, potassium, or estimated glomerular filtration rate when using sodium picosulfate-magnesium citrate catharsis prior to CTC [37]. Finally, although it has been suggested that bacteria introduced during colonography could risk infection of prosthetic vascular grafts, a study of 100 consecutive patients subject to serial blood cultures following CTC failed to showed significant bacteremia, and suggested antibiotic prophylaxis is not required [38].

Who Should Report CT Colonography? Interpreting CTC has become more attractive to nonradiologists such as gastroenterologists and radiographic technicians. In part, this is driven by advances in medical image display, which mean rapid high quality threedimensional endoluminal visualizations of CTC datasets are easily accessible and will appear familiar to clinicians already performing endoscopy. Young et al. [39] sought to determine whether a suitably trained group of gastroenterologists could interpret CTC using a small subset of cases from the Department of Defence (DoD) screening trial [2]. Following a single, 45-min training session, the gastroenterologists identified polyps larger than 6 and 10 mm with a mean sensitivity of 84% and 88% respectively. The authors concluded that the observers in their study were able to read CTC with an accuracy

Curr Gastroenterol Rep (2011) 13:486–494

approaching that of radiologists. However, the study also reported a relatively low per-patient specificity for nondiminutive polyps (of 70%) and an accompanying commentary [40] , stressed that the challenge in reporting CTC lies not only in attaining high sensitivity, but also in the correct dismissal of false positive lesions, which requires cross-sectional imaging expertise. In contrast, because of pressure of work, European radiologists have studied the feasibility of delegating CTC interpretation to radiographic technicians, albeit with the assistance of computer aided detection (CAD) software [41]. Radiographic technicians performed the primary interpretation in 303 consecutive symptomatic patients detecting 100% cancers, 72% of large polyps (≥10 mm) and 70% medium sized (6–9 mm) polyps. However, once again, observer specificity was poor and would have resulted in inappropriate referral for colonoscopy in 37% of the patients studied. Overall, the authors concluded that CTC interpretation by radiographic technicians may be useful for rapid patient triage post procedure, but ultimately not for independent reporting.

Extra-Colonic Findings One factor that cannot be ignored when considering who should report CTC is the potentially high prevalence of incidental extra-colonic findings. For example, a retrospective review of 10,286 outpatient adults undergoing screening CTC [9•] reported 36 unexpected extra-colonic malignancies (0.35%) including 11 renal cell carcinomas, eight lung cancers, and six cases of non-Hodgkin’s lymphoma. Intuitively, the serendipitous discovery of incidental extra-colonic malignancy should benefit patients, yet long-term data on improved patient outcomes are currently lacking. Perhaps unsurprisingly, a survey of 476 participants attending training at European CTC workshops found 83% of respondents believed that detection of extracolonic findings was beneficial in symptomatic patients [29•]. However, the additional cost and patient morbidity from the work-up of extra-colonic findings is likely to be considerable. A recent study of 2777 screening patients identified extra colonic findings in 46%, and “significant” findings in 11%. [42] Further evaluation resulted in 280 radiological examinations and 19 surgeries. In addition, Pickhardt et al. [43] assessed incidental indeterminate adnexal masses in 2869 asymptomatic women undergoing colonography screening and found that while ovarian lesions were common (4.1%), subsequent work-up revealed no ovarian cancers. Moreover, a normal CTC did not exclude subsequent development of ovarian cancer. Finally, as noted above, Markov modelling has predicted that

Curr Gastroenterol Rep (2011) 13:486–494

detection of unsuspected aortic aneurysm in a screening program would significantly increase both lives saved and cost effectiveness [24•].

Future Developments Computer Aided Detection The time-consuming, laborious nature of CTC interpretation together with the well documented problems of perceptive error make it an ideal candidate to benefit from computer aided detection (CAD) software. CAD algorithms have been developed by several groups and increasing data are emerging both on their performance characteristics and their effect on radiologist accuracy. Although it is generally accepted that using CAD as a “first reader” (whereby radiologists review just those regions of the colon annotated by the software) remains unfeasible (and undesirable) at present, the algorithm’s standalone performance is usually quoted to assess its detection characteristics and gauge its potential subsequent impact on interpretative accuracy. For example, a recent retrospective study of a cohort of 3042 screening patients, 373 of whom had medium or large polyps, found standalone per-patient sensitivities for CAD of 94% and 97% at 6 and 10 mm thresholds, respectively [44] (Fig. 1). Moreover, the median false-positive rate was only 3 per CTC series. Similar high levels of CAD

Fig. 1 Axial supine CT colonography with oral contrast; 2D reconstruction using colonography window settings. A 27 mm polyp is present in the cecal pole. Computer-aided detection (CAD) has correctly labelled the polyp with a discrete prompt (arrow). The ileo-cecal valve (arrowhead) has a typical lobular appearance and should not be confused with pathology

491

performance was obtained in a much smaller study of 29 patients at high-risk of colorectal neoplasia (with 86 polyps) [45]. However, excellent standalone performance does not necessarily translate into equivalent levels of diagnostic accuracy when integrated with radiologist interpretation in daily clinical practice. There are likely two main reasons for this: readers may be misled by false positive CAD prompts, reducing their specificity, or they may incorrectly classify a true positive CAD prompt as false-negative, reducing potential gains in sensitivity. Taylor et al. [46] examined 111 polyps that had been incorrectly dismissed by radiologists in previous studies, despite appropriate CAD prompting. Size, morphology, location, bowel preparation, and CADprompt conspicuity were assessed. The authors found larger polyps with unusual morphology were most likely to be incorrectly dismissed. A further study of 33 cases containing 21 polyps found that true positive CAD prompts were more likely to be correctly classified by readers when prompts were present on both the corresponding prone and supine scans [47]. Therefore, there is growing interest in automating the registration task between prone and supine acquisitions [48]. Two groups have recently published multi-reader, multicase studies using CAD as a “second reader,” ie the CAD prompts are only interrogated by the reader after a thorough unassisted review has first been performed. Dachman et al. [49•] used a cohort of 100 endoscopically-validated cases, 48 of which were normal and 52 of which contained 74 polyps. A total of 19 readers interpreted each case unassisted and with CAD as a second-reader. Readers’ per-segment, per-patient, and per-polyp sensitivity were higher (P<0.011, 0.007, 0.005, respectively) with CAD compared to unassisted readings. However CAD reduced readers’ specificity by 0.025 (P=0.05). Halligan et al. [50•] found similar results. A total of 16 experienced radiologists interpreted CTC from 112 patients (132 polyps in 56 patients) on three separate occasions either unassisted, using CAD concurrently (ie, at the same time as the primary analysis), or with CAD as a second-reader. CAD significantly increased mean per-patient sensitivity both when used as a second-reader (mean increase, 7.0%; 95% confidence interval [CI]: 4.0–9.8%), or when used concurrently (mean increase, 4.5%; 95% CI: 0.8–8.2%). Furthermore, CAD resulted in no significant decrease in per-patient specificity for these readers. These are the largest reader studies of CAD to date and argue strongly that CAD would be beneficial if used in clinical practice by experienced radiologists. PET-CT Uptake of F-FDG by colonic neoplasia is well described, but the advantage of combining of PET and CTC remains

492

uncertain. Taylor et al. [51] performed a pilot study of 56 patients at increased risk of colorectal neoplasia undergoing combined non-laxative PET/CT. An experienced radiologist and a nuclear medicine physician analyzed the datasets in consensus. Compared with colonoscopy, CTC had sensitivity of 93% for medium and large polyps, and while this was not improved by the addition of PET, combined PET/ CTC increased per-patient positive predictive value for large polyps from 73% to 100%. The authors concluded that simultaneous PET acquisition during non-laxative CTC is technically feasible, well tolerated, and could potentially improve diagnostic accuracy.

Conclusions Recent research has continued to demonstrate that CTC has excellent sensitivity compared to colonoscopy, and is significantly more accurate than barium enema, which should be abandoned for colorectal cancer screening purposes. Adverse events are uncommon and patient acceptability is good. Reduced bowel preparation regimens continue to show considerable promise. Evidence is mounting that the impressive stand-alone detection rates of CAD translate into improved radiologist accuracy. Controversy continues regarding the impact of incidental extra-colonic detections, who should interpret CTC, whether compliance with screening programs is genuinely enhanced by CTC, and whether the technique is ultimately cost effective. Acknowledgments This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.

Disclosure Steve Halligan and Stuart A. Taylor have worked as research consultants for Medicisight PLC; Darren Boone reported no potential conflicts of interest relevant to this article.

References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1. •• Johnson CD, Chen M-H, Toledano AY, et al. Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med 2008;359(12):1207–17. This large, prospective, multicentre trial evaluated CTC performance in average risk asymptomatic patients. Compared to the colonoscopic reference standard, CTC had excellent sensitivity for cancer and large adenomas.

Curr Gastroenterol Rep (2011) 13:486–494 2. Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med. 2003;349(23):2191–200. 3. Kim DH, Pickhardt PJ, Taylor AJ, et al. CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med. 2007;357(14):1403–12. 4. Halligan S, Altman DG, Taylor SA, et al. CT colonography in the detection of colorectal polyps and cancer: systematic review, meta-analysis, and proposed minimum data set for study level reporting. Radiology. 2005;237(3):893–904. 5. •• Taylor SA, Halligan S, Atkin W et al. Clinical trials and experiences: SIGGAR. Presented at the 11th International Symposium on Virtual Colonoscopy. Westin Copley Place, Boston, MA. October 25–27, 2010. Randomized controlled trial comparing CTC to barium enema and colonoscopy for detecting large polyps or cancer in symptomatic patients. Preliminary results have prompted the UK Department of Health to withdraw barium enema from its national screening program. 6. U.S. Preventive Services Task Force Recommendation Statement. Screening for colorectal cancer. Ann Intern Med. 2008;149 (9):627–37. 7. Levin B, Lieberman DA, McFarland B, et al. 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. Gastroenterology. 2008;134(5):1570–95. 8. Knudsen AB, Lansdorp-Vogelaar I, Rutter CM, et al. Costeffectiveness of computed tomographic colonography screening for colorectal cancer in the medicare population. J Natl Cancer Inst. 2010;102(16):1238–52. 9. • Pickhardt PJ, Kim DH, Meiners RJ, et al. Colorectal and extracolonic cancers detected at screening CT colonography in 10,286 asymptomatic adults. Radiology 2010;255(1):83–8. A retrospective evaluation of cancer detection rates in over 10000 CTC screening patients. Overall, one in 500 asymptomatic individuals was shown to have invasive colorectal cancer and one in 300 had extracolonic cancer. 10. •• Regge D, Laudi C, Galatola G, et al. Diagnostic accuracy of computed tomographic colonography for the detection of advanced neoplasia in individuals at increased risk of colorectal cancer. JAMA: J Am Med Assoc 2009;301(23):2453–61. This multicentre study demonstrated good diagnostic performance when using CTC to investigate patients at increased risk of developing colorectal cancer such as those with a family history of advanced neoplasia or positive fecal occult blood test. 11. •• Graser A, Stieber P, Nagel D, et al. Comparison of CT colonography, colonoscopy, sigmoidoscopy and faecal occult blood tests for the detection of advanced adenoma in an average risk population. Gut 2009;58(2):241–8. A prospective, withinsubject comparison of CTC, colonoscopy, FOBT, and flexible sigmoidoscopy. CTC achieved a remarkably high sensitivity for detecting polyps with advanced histological features during screening of average risk individuals. 12. Halligan S, Lilford RJ, Wardle J, et al. Design of a multicentre randomized trial to evaluate CT colonography versus colonoscopy or barium enema for diagnosis of colonic cancer in older symptomatic patients: the SIGGAR study. Trials. 2007;8:32. 13. • Halligan S, Waddingham J, Dadswell E, et al. SIGGAR trial investigators: detection of extracolonic lesions by CTC in symptomatic patients: their frequency and severity in a randomised controlled trial. Eur Radiol 2010;20(Suppl 1):S8. Important extracolonic findings were considerably more prevalent in this randomized controlled trial of symptomatic patients than in previous studies which have examined screening populations.

Curr Gastroenterol Rep (2011) 13:486–494 14. Sali L, Falchini M, Della Monica P, et al. CT colonography before colonoscopy in subjects with positive faecal occult blood test. Preliminary experience. Radiol Med. 2010;115(8):1267–78. 15. Benson M, Dureja P, Gopal D, et al. A comparison of optical colonoscopy and ct colonography screening strategies in the detection and recovery of subcentimeter adenomas. Am J Gastroenterol. 2010;105(12):2578–85. 16. • Hassan C, Pickhardt PJ, Kim DH, et al. Systematic review: distribution of advanced neoplasia according to polyp size at screening colonoscopy. Aliment Pharmacol Ther 2010;31(2):210– 7. This methodological literature review provides estimates of advanced histological features from over 20000 colonoscopic polypectomy specimens. Referral size thresholds for CTC are suggested. 17. de Vries AH, Bipat S, Dekker E, et al. Polyp measurement based on CT colonography and colonoscopy: variability and systematic differences. Eur Radiol. 2010;20(6):1404–13. 18. Ignjatovic A, Burling D, Ilangovan R, et al. Flat colon polyps: what should radiologists know? Clinical Radiology. 2010;65 (12):958–66. 19. Pickhardt PJ, Kim DH, Robbins JB. Flat (nonpolypoid) colorectal lesions identified at CT colonography in a U.S. screening population. Acad Radiol. 2010;17(6):784–90. 20. Dhruva SS, Phurrough SE, Salive ME, Redberg RF. CMS’s landmark decision on CT colonography–examining the relevant data. N Engl J Med. 2009;360(26):2699–701. 21. Pickhardt PJ, Kim DH, Hassan C. Re: cost-effectiveness of computed tomographic colonography screening for colorectal cancer in the medicare population. J Natl Cancer Inst. 2010;102 (21):1676. 22. Moawad FJ, Maydonovitch CL, Cullen PA, et al. CT colonography may improve colorectal cancer screening compliance. AJR Am J Roentgenol. 2010;195(5):1118–23. 23. Ho W, Broughton DE, Donelan K, et al. Analysis of barriers to and patients’ preferences for CT colonography for colorectal cancer screening in a nonadherent urban population. AJR Am J Roentgenol. 2010;195(2):393–7. 24. • Pickhardt PJ, Hassan C, Laghi A, Kim DH. CT Colonography to screen for colorectal cancer and aortic aneurysm in the medicare population: cost-effectiveness analysis. Am J Roentgenol 2009;192(5):1332–40. The additional financial burden of investigating incidental extracolonic pathology remains the subject of debate. This modelling exercise focuses on abdominal aortic aneurysms, suggesting their detection will improve costeffectiveness of a potential CTC screening program. 25. Cash BD. CT colonography: ready for prime time? Am J Gastroenterol. 2010;105(10):2128–32. 26. Schoen RE, Hashash JG. Con: CT colonography-not yet ready for community-wide implementation. Am J Gastroenterol. 2010;105 (10):2132–7. 27. Burke CA. A balancing view: the good, the bad, and the unknown. Am J Gastroenterol. 2010;105(10):2137–8. 28. • Fletcher JG, Chen MH, Herman BA, et al. Can radiologist training and testing ensure high performance in CT colonography? Lessons from the National CT Colonography Trial. AJR Am J Roentgenol 2010;195(1):117–25. This interesting study compared observer performance in a CTC test set (before and after focused training) with their performance in a prospective screening study. 29. • Boone D, Halligan S, Frost R, et al. CT colonography: who attends training? A survey of participants at educational workshops. Clin Radiol 2011. In press. This survey suggests the level of training and experience among those interpreting CT colonography in daily practice falls short of consensus recommendations. 30. • Burling D. CT colonography standards. Clin Radiol 2010;65 (6):474–80. This document supersedes the 2007 European

493

31.

32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

46.

(ESGAR) consensus statement summarizing best practice guidelines for CTC implementation. •• McFarland EG, Fletcher JG, Pickhardt P, et al. ACR Colon Cancer Committee white paper: status of CT colonography 2009. J Am Coll Radiol 2009;6(11):756–72.e4. This thorough review considers the evidence for CTC performance, training and certification, colonic and extracolonic reporting, quality metrics and cost-effectiveness. Von Wagner C, Halligan S, Atkin WS, et al. Choosing between CT colonography and colonoscopy in the diagnostic context: a qualitative study of influences on patient preferences. Health Expectations. 2009;12(1):18–26. Jensch S, Bipat S, Peringa J, et al. CT colonography with limited bowel preparation: prospective assessment of patient experience and preference in comparison to optical colonoscopy with cathartic bowel preparation. Eur Radiol. 2010;20 (1):146–56. • Mahgerefteh S, Fraifeld S, Blachar A, Sosna J. CT colonography with decreased purgation: balancing preparation, performance, and patient acceptance. AJR Am J Roentgenol 2009;193(6):1531– 9. Systematic review of studies that prospectively compare acceptability and performance of reduced laxative CTC with optical colonoscopy. • Atalla MA, Rozen WM, Niewiadomski OD, et al. Risk factors for colonic perforation after screening computed tomographic colonography: a multicentre analysis and review of the literature. J Med Screen 2010;17(2):99–102. Systematic review supplemented by a multicentre analysis to estimate the perforation risk during 3458 screening CTC examinations. Cha EY, Park SH, Lee SS, et al. CT colonography after metallic stent placement for acute malignant colonic obstruction. Radiology. 2010;254(3):774–82. Mc Laughlin P, Eustace J, Mc Sweeney S, et al. Bowel preparation in CT colonography: electrolyte and renal function disturbances in the frail and elderly patient. Eur Radiol. 2010;20(3):604–12. Ridge CA, Carter MR, Browne LP, et al. CT colonography and transient bacteraemia: implications for antibiotic prophylaxis. Eur Radiol. 2010;21(2):360–5. Young PE, Ray QP, Hwang I, et al. Gastroenterologists’ interpretation of CTC: a pilot study demonstrating feasibility and similar accuracy compared with radiologists’ interpretation. Am J Gastroenterol. 2009;104(12):2926–31. Pickhardt PJ. Editorial: CTC interpretation by gastroenterologists: feasible but largely impractical, undesirable, and misguided. Am J Gastroenterol. 2009;104(12):2932–4. Burling D, Wylie P, Gupta A, et al. CT colonography: accuracy of initial interpretation by radiographers in routine clinical practice. Clin Radiol. 2010;65(2):126–32. Veerappan GR, Ally MR, Choi JH, et al. Extracolonic findings on CT colonography increases yield of colorectal cancer screening. AJR Am J Roentgenol. 2010;195(3):677–86. Pickhardt PJ, Hanson ME. Incidental adnexal masses detected at low-dose unenhanced CT in asymptomatic women age 50 and older: implications for clinical management and ovarian cancer screening. Radiology. 2010;257(1):144–50. Lawrence EM, Pickhardt PJ, Kim DH, Robbins JB. Colorectal polyps: stand-alone performance of computer-aided detection in a large asymptomatic screening population. Radiology. 2010;256 (3):791–8. Wi JY, Kim SH, Lee JY, et al. Electronic cleansing for CT colonography: does it help CAD software performance in a highrisk population for colorectal cancer? Eur Radiol. 2010;20 (8):1905–16. Taylor SA, Robinson C, Boone D, et al. Polyp characteristics correctly annotated by computer-aided detection software but

494 ignored by reporting radiologists during CT colonography. Radiology. 2009;253(3):715–23. 47. Summers RM, Liu J, Rehani B, et al. CT colonography computeraided polyp detection: effect on radiologist observers of polyp identification by CAD on both the supine and prone scans. Acad Radiol. 2010;17(8):948–59. 48. Roth H, McClelland J, Modat M, et al. Establishing spatial correspondence between the inner colon surfaces from prone and supine CT colonography. Med Image Comput Comput Assist Interv. 2010;13(Pt 3):497–504. 49. • Dachman AH, Obuchowski NA, Hoffmeister JW, et al. Effect of computer-aided detection for CT colonography in a multireader, multicase trial. Radiology 2010;256(3):827–35. Multi-

Curr Gastroenterol Rep (2011) 13:486–494 observer study using computer aided detection as “second reader”. 50. • Halligan S, Mallett S, Altman DG, et al. Incremental benefit of computer-aided detection when used as a second and concurrent reader of CT colonographic data: multiobserver study. Radiology 2011; 258(2):469–76. A further, large multicenter, multi-observer study assessing the added benefit provided to experienced readers when computer aided detection is employed as “second reader” or “concurrent reader”. 51. Taylor SA, Bomanji JB, Manpanzure L, et al. Nonlaxative PET/ CT colonography: feasibility, acceptability, and pilot performance in patients at higher risk of colonic neoplasia. J Nucl Med. 2010;51(6):854–61.