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CT colonography: accuracy, acceptance, safety and position in organised population screening
  1. Margriet C de Haan1,2,
  2. Perry J Pickhardt3,
  3. Jaap Stoker1
  1. 1Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
  2. 2Department of Radiology, University Medical Center, Utrecht, The Netherlands
  3. 3Department of Radiology, University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, USA
  1. Correspondence to Dr Margriet C de Haan, Department of Radiology, Academic Medical Center, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands; margrietcdehaan{at}gmail.com

Abstract

Colorectal cancer (CRC) is the second most common cancer and second most common cause of cancer-related deaths in Europe. The introduction of CRC screening programmes using stool tests and flexible sigmoidoscopy, have been shown to reduce CRC-related mortality substantially. In several European countries, population-based CRC screening programmes are ongoing or being rolled out. Stool tests like faecal occult blood testing are non-invasive and simple to perform, but are primarily designed to detect early invasive cancer. More invasive tests like colonoscopy and CT colonography (CTC) aim at accurately detecting both CRC and cancer precursors, thus providing for cancer prevention. This review focuses on the accuracy, acceptance and safety of CTC as a CRC screening technique and on the current position of CTC in organised population screening. Based on the detection characteristics and acceptability of CTC screening, it might be a viable screening test. The potential disadvantage of radiation exposure is probably overemphasised, especially with newer technology. At this time-point, it is not entirely clear whether the detection of extracolonic findings at CTC is of net benefit and is cost effective, but with responsible handling, this may be the case. Future efforts will seek to further improve the technique, refine appropriate diagnostic algorithms and study cost-effectiveness.

  • COLORECTAL CANCER SCREENING
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Key messages

  • CT colonography (CTC) has a comparable sensitivity with colonoscopy for colorectal cancer (CRC) and large precursor adenomas (≥10 mm).

  • CTC screening with a referral cut-off of 10 mm and larger, results in a higher participation rate than colonoscopy screening and a similar yield per invitee.

  • CTC has a low complication rate.

  • Radiation risk is a relative disadvantage of CTC screening; nonetheless, it is estimated that for each theoretically induced carcinoma, at least 24 CRCs are prevented.

  • CTC represents an effective additional screening option to colonoscopy that provides for cancer prevention and detection.

Introduction

Colorectal cancer (CRC)-related mortality can be reduced by the implementation of CRC screening programmes as has been demonstrated for stool tests (16%) and flexible sigmoidoscopy (FS, 22%–31%).1–5 Randomised trials on the effectiveness of colonoscopy are ongoing, and first results will not be available before 2020.6 ,7 Stool tests, like faecal occult blood testing (FOBT), are non-invasive and simple to perform, but are primarily designed to detect early invasive cancer. More invasive tests, like colonoscopy, aim at accurately detecting both CRC and cancer precursors (ie, advanced adenomas) as well, thus providing for cancer prevention. CT colonography (CTC) has been introduced as a full colon examination similar to colonoscopy but is less invasive. For both colonoscopy and CTC—being full colon evaluation techniques with direct visualisation of target lesions—it is highly plausible that both colonoscopy and CTC screening would result in a further decrease of CRC-related mortality compared with stool-based tests and sigmoidoscopy. Many aspects of CTC have been extensively studied. This review focuses on the accuracy, acceptance and safety of CTC as a CRC screening technique and on the current position of CTC in organised population screening.

Accuracy in screening

A meta-analysis published in 2011 showed that CTC has an estimated per-patient sensitivity of 80% for adenomas ≥6 mm and of 88% for advanced neoplasia ≥10 mm (including both advanced adenomas and invasive cancer) based on the aggregated results of five CTC screening studies (figures 13).8–14 This meta-analysis predominantly included data on average-risk participants (n=4086, <1% high risk), defined as individuals who were asymptomatic, had no family history of CRC and no personal history of polyps, CRC or IBD. Three of the five screening studies reported per-patient sensitivities for advanced neoplasia ≥6 mm ranging from 84% to 93% (data only provided in De Haan et al8). One further study published after this review showed similar results.15 No CRCs were missed by CTC in these six screening trials.9–15 The high sensitivity of CTC for the detection of CRC was confirmed by a meta-analysis including studies on both average and high-risk participants, showing a sensitivity of 96% for CRC.16 Colonoscopy, on the other hand, has a per-patient sensitivity of 92% for adenomas ≥6 mm, of 88% for advanced neoplasia ≥10 mm and of 95%–97% for CRC.13 ,17 These data indicate that CTC and colonoscopy have a comparable sensitivity for CRC and CRC precursor lesions of 10 mm and larger.

Figure 1

Large pedunculated advanced adenoma (tubulovillous adenoma with high-grade dysplasia) in an asymptomatic 54-year-old man undergoing routine CT colonography (CTC) screening. (A) Three dimensional (3D) colon map shows the precise location of the polyp in the sigmoid colon (red dot with blue arrow), which is provided to the gastroenterologist to guide polypectomy. (B and C) Transverse two dimensional (2D) images with polyp (B) and soft tissue (C) windowing shows the lobulated soft tissue lesion in the sigmoid colon (arrow). Note the coating of the lesion surface with oral contrast, which can aid in detection at CTC. (D) 3D endoluminal CTC image better depicts the thin stalk of this pedunculated lesion, which measured 2.8 cm. (E) Image from same-day optical colonoscopy for polypectomy. The mucus cap seen at optical colonosccopy corresponds to the oral contrast coating seen at CTC. Tubulovillous adenoma with high-grade dysplasia was found at pathology.

Figure 2

Early asymptomatic cancer detected in a 51-year-old man. (A) Three dimensional (3D) endoluminal image that simulates the retroflexed anorectal view at optical colonoscopy shows a relatively flat 2 cm lesion (arrowheads) adjacent to the rectal catheter. (B and C) Transverse two dimensional (B) and endoluminal 3D (C) images suggest a shallow central depression to this rectal lesion (arrowhead). (D) Endoscopic image confirms the presence and morphology of the 2 cm lesion, which contained a focus of invasive adenocarcinoma at biopsy. (E) Transrectal ultrasound suggests a superficial T1 lesion (calipers), which was confirmed at pathology after resection (T1N0M0). The patient is doing well 4 years later, without evidence of recurrence.

Figure 3

Large right-sided serrated lesion (traditional serrated adenoma with high-grade dysplasia) found at screening CT colonography (CTC) in a symptomatic 56-year-old man. (A and B) Supine two dimensional (2D) (A) and three dimensional (3D) (B) CTC images show a relatively flat-appearing 3.5 cm lesion (arrowheads) near the hepatic flexure. (C and D) Prone 2D (C) and 3D (D) CTC images show that the lesion is not sessile but rather drapes broadly into the lumen. Note the unusual palisading appearance of contrast extending into crevices of this lobulated lesion. (E) Image from same-day optical colonoscopy shows a lobulated appearance. The mucus coating again corresponds to the oral contrast seen at CTC.

Diminutive polyps

The main goal of CTC screening is to detect advanced adenomas, as the majority of CRCs develop from these.18 The majority of lesions smaller than 6 mm, the so-called diminutive lesions, are hyperplastic or tubular adenomas of little or no clinical significance.19 The chance of these lesions being malignant or containing high-grade dysplasia at the time of detection is estimated to be much <1%.20 Referring CTC-detected diminutive lesions to polypectomy is not a clinically efficacious or cost-effective strategy.21 ,22 Reporting of these small lesions at CTC is, therefore, not recommended.23

Flat polyps

Although the majority of intracolonic lesions has a sessile or polypoid morphology, a considerable minority is flat. A US study including data of 5107 screening subjects showed that 13% of 954 detected polyps were flat, but also showed that this type of lesions were less likely to have advanced histology compared with polypoid lesions of similar size.24 This is an important finding, as lesions with a flat morphology are more difficult to visualise during endoscopy as well as on CTC. Most studies on the sensitivity of CTC for flat lesions are characterised by small sample sizes. A Korean study comparing CTC with colonoscopy, reported that CTC detected 12 (67%) of 18 flat advanced neoplastic lesions.25 These findings confirmed a previous Korean study, which observed that the sensitivity of CTC for detection of flat polyps was <50%.26 Lesions had to have a minimum height of 2 mm and a diameter of 7 mm before CTC could detect them. Once flat lesions reach 3 cm in diameter, they may be termed ‘carpet lesions’ and are more readily detectable at CTC.27 One useful feature for detecting flat lesions is the propensity for oral contrast to coat the lesional surface, which increases the conspicuity at CTC.27 ,28

Flat lesions can be divided in the more common superficially elevated type, and the more rare depressed type. It has been shown that depressed lesions are more important than other flat lesions, as they more often contain high-grade dysplasia or invasive carcinoma beyond the submucosal layer than other flat lesions.29 These results were in line with the results of a Japanese study showing that invasive cancer rates in lesions between 6 and 10 mm were 0.18% in flat elevated lesions, while 43.2% of depressed lesions in the same size category contained invasive cancer.30 In a screening cohort of 1233 subjects, no depressed flat lesions were detected, suggesting that the incidence of relevant flat lesions is low in screening cohorts.31 This was confirmed by a study published in 2008, showing a prevalence for depressed colorectal neoplasia of 0.18%29 based on the colonoscopy screening results of 8372 average-risk subjects.

Reading strategy

CTC can be evaluated on 2D images with or without 3D problem-solving or by using primary 3D evaluation with 2D problem-solving (figures 14). The primary 2D read strategy is faster than primary 3D read and requires no special expertise on advanced 3D interpretation techniques. However, a large screening study showed that when less experienced readers use 3D as primary evaluation technique, their sensitivity for intracolonic findings is higher compared with their sensitivity with primary 2D read.13 ,32 Another large screening study from Johnson et al10 showed no significant difference between primary 2D and 3D reading strategies. At this point, there is still conflicting evidence regarding the possible difference of sensitivity using primary 2D or 3D read. The best strategy is probably to use both 2D and 3D for lesions detection, as they are likely complementary.

Figure 4

Extracolonic malignancy (primary peritoneal high-grade papillary serous carcinoma) developing rapidly in a 55-year-old woman undergoing surveillance CT colonography (CTC) for a small 6 mm polyp detected at initial CTC screening two years earlier. (A and B) Three dimensional (3D) endoluminal image (A) from the initial CTC screening study shows a small 6 mm polyp (blue region) in the sigmoid colon, which is shown as marked by the automatic computer-aided detection (CAD) algorithm. Two dimensional (2D) transverse CTC image (B) through the upper abdomen shows excellent colonic distention and no extracolonic abnormalities. (C and D) 2D CTC image (C) from polyp surveillance study performed 2 years later shows interval development of omental caking (arrowheads) and serosal thickening of the transverse colon by the primary peritoneal tumour (arrow). 3D endoluminal view (D) from the vantage point of the blue arrow in C shows extrinsic luminal narrowing with preservation of the mucosal surface. The 6 mm sigmoid polyp (not shown) was stable in size and no other intrinsic colonic abnormalities were seen. Such detection of unsuspected extracolonic cancer at CTC is a more common occurrence than colorectal cancer among asymptomatic adults.

Computer aided detection

The main objective of the use of computer aided detection (CAD) is to identify lesions that have been missed by the observer (figure 4). Regge et al33 have shown in a prospective study with low-risk individuals that double reading with CAD, as second reader significantly improves the sensitivity for 6–9 mm polyps compared with unassisted interpretation by one radiologist (from 65% to 77%) at the expense of a longer reporting time, indicating that CAD is very useful as second reader. CAD might also be considered as a first-reader technique or as stand-alone. However, most studies on evaluating these strategies in a screening population used retrospective study designs. Further, medicolegal issues will be a hurdle for primary CAD reads.

Experience of CTC observers

The yield of CTC, as with any imaging technique, is observer-dependent. A retrospective analysis of routinely collected data in the English Bowel Cancer Screening Program showed that the detection rate and positive predictive value of CTC are significantly higher at centres with experienced radiologists (>1000 examinations) and at centres with more than 175 cases per radiologist per year.34 This finding is in line with the results of a Dutch study in which six physicians and three radiographers were trained by means of a structured training programme.35 The average sensitivity for detection of lesions 6 mm or larger increased significantly from 76% in the first set of 50 CTC examinations to 91% in the fourth. The estimated number of CTC examinations for a sufficient sensitivity was 164, suggesting that sufficient training requires at least 164 training cases. However, among radiologists experienced with CTC, Pooler et al36 showed a much more uniform performance among radiologists for polyp detection compared with published variation among gastroenterologists at colonoscopy.

CTC screening: attendance, diagnostic yield and adherence

In a screening trial performed in the USA, approximately 8% of 3120 CTC screenees were referred for colonoscopy, leading to detection of advanced neoplasia in 3.2% of CTC screenees, compared with 3.4% of 3163 colonoscopy screenees (figures 13).37 The yield per 100 participants was higher within a randomised screening trial performed in the Netherlands where 2920 individuals were invited: 8.7 per 100 colonoscopy participants and 6.1 per 100 CTC participants.38 Here, only CTC participants with one or more lesions ≥10 mm were referred for colonoscopy, and those with 6–9 mm lesions were offered CTC surveillance. Of note, this trial reported a significantly higher participation rate for CTC than for colonoscopy: 34% and 22%, respectively (a 55% increase). Although the diagnostic yield per participant was higher in colonoscopy, the diagnostic yield for advanced neoplasia per invitee was similar due to the higher uptake in CTC screening: 1.9 per 100 colonoscopy invitees versus 2.1 per 100 CTC invitees. This illustrates the importance of considering the ultimate diagnostic yield per invitee between different screening techniques, rather than simply the differences in accuracy. First-round sigmoidoscopy screening resulted in a comparable yield (2.2 per 100 invitees), as well as first-round faecal immunochemical test (FIT) screening (2.0/100) when using a cut-off of 50 ngHb/mL.39

In most countries, FIT screening is repeated at 2-year intervals, whereas colonoscopy and sigmoidoscopy screening are repeated every 5–10 years. For CTC, similar 5-year to10-year intervals might be used.40 At this point, the question remains whether the adherence to screening will be comparable in different rounds and whether cumulative yield of the different screening rounds will be approximately the same for each screening technique after a screening period for 10 or 20 years, for example. The adherence to a two-round FIT screening over 2 years was not significantly different between two screening rounds, the diagnostic yield of the second screening round was significantly lower compared with the first round.41 To our knowledge, no studies have been published on the adherence to, and the diagnostic yield of, CTC screening when applied every 5 or 10 years. Surveillance adherence data from the Dutch population-based CTC screening trial will probably be available soon. Data on the diagnostic yield from the second round of screening with CTC at 5–10 years is also expected within the next year or so from the University of Wisconsin CTC screening programme.

Acceptance

Attendance to screening is influenced by the expected burden, illustrated by the results of a Dutch population-based screening trial comparing the participation in colonoscopy and CTC screening.38 Invitees were asked to fill out a questionnaire in which they could indicate the reasons for accepting or declining their invitation. Almost half the non-screenees had adequate knowledge on CRC screening and expressed a positive attitude towards screening, suggesting the existence of additional barriers towards participation.42 Both in colonoscopy and CTC screening, the most cited reasons to decline screening were the expected unpleasantness of the examination and the expected inconvenience of the preparation.43 However, the most decisive reason in colonoscopy was ‘unpleasantness of the examination’ while CTC non-screenees indicated ‘no time/too much effort’ and ‘lack of symptoms’ as most decisive reasons.43 Ho et al44 found similar results for CTC in the USA: 38% of non-screenees declined screening due to procrastination and 12% because they were too busy.

The adherence in future screening rounds is probably influenced by the experienced burden in previous screening rounds. In 2012, a meta-analysis was published including 23 studies in both average and high-risk subjects who underwent colonoscopy as well as CTC, presenting data on differences in burden and preferences for colonoscopy or CTC after receiving both examinations.45 Only three studies showed a significant preference for colonoscopy, while 16 studies showed a significant preference for CTC. Studies in screening populations and studies in which the subjects were aware of the a priori probability of the need for a follow-up colonoscopy after CTC, showed a stronger preference for CTC. Four screening studies compared the perceived burden using a tandem design, showing that 46%–95% of screenees preferred CTC the next time.9 ,46–48 However, a recent population-based screening trial showed that CTC participants experienced their examination as slightly more burdensome than colonoscopy participants.49 The clinical relevance of this difference is questionable, as the pooled SD of the scores was 0.9, indicating a large within-group variability in scores. Further, the arms were not randomised for evaluating burden and concerned groups that were not identical, thus hampering comparison. Importantly, the intended participation in a next screening round was more than 90% for both procedures among screenees.

Guidelines for CTC practice

Recently, the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) published a consensus statement on quality standards for CTC.50 The American College of Radiology also recently updated its practice guidelines for CTC.51 Both statements indicate that the patient should be prepared with a low fibre diet and with laxative agents, if possible, prior to the examination. Faecal tagging with iodine or barium is mandatory, as untagged fluid or faecal residue can lead to false-positive or false-negative findings. A thin and flexible rectal tube is recommended for colonic distension. When using a small rectal balloon, this should be deflated in one scan acquisition to prevent masking of a rectal lesion. Automated insufflation of carbon dioxide is the preferred method for colonic distension, as it maximises patient comfort during and after the procedure and improves distension. Prior to colonic distension, some advise the use of 1 mL intravenously administered butylscopolamine as spasmolytic (where available), unless contraindicated. Generally, spasmolytics are not employed for CTC in the USA, while these are widely used in Europe. Image acquisition includes a scan in supine and prone position on a multidetector CT scanner (≥4) using a low radiation dose protocol. Intravenous contrast medium is not required in screening.

Risks of CTC

One of the main concerns regarding the use of CTC as screening technique is the exposure of screenees to ionising radiation, which is known to be associated with the risk of cancer induction at much higher doses. However, the small theoretical risk related to low-dose medical exposures should be balanced against the benefit related to prevented cancers. Berrington de González et al52 compared the expected number of induced and prevented cancers by using the effective dose of a 5-yearly CTC screening programme (8 mSv for women and 7 mSv for men). They estimated that at least 24–35 CRCs would be prevented for every radiation-induced cancer, depending on the model used. Nowadays, the average dose of screening CTC is even lower (4.4 mSv), and the routine surveillance interval is typically in the 5–10 years range, making the benefit-risk ratio even more favourable.53 New developments, like decreasing tube current and voltage, and using iterative reconstruction algorithms lead to further dose reduction, below 1 mSv.54 With these developments, the risk of ionising radiation from CTC for the population considered for screening is extremely low and likely negligible or non-existent.

CTC has a low risk of major complications due to the examination itself.55 A review including 50 860 subjects receiving a CTC because of symptoms or for screening purposes indicated that CTC has a total perforation rate of 0.035% (ie, 18 of 50 860, which includes asymptomatic extracolonic gas that required no treatment) and a symptomatic perforation rate of 0.015%, while primary colonoscopy screening has a symptomatic perforation rate ranging from 0.2% to 0.02%.13 ,55–57 Of the 18 subjects with a perforation caused by CTC, 15 occurred with manual insufflation that is no longer state-of-the-art. A large Italian study published after this review showed that asymptomatic bowel perforations occurred in seven (0.02%) of 40 121 CTCs (both screening and diagnostic), one of these patients had an earlier colonoscopy with a biopsy 2 weeks before the CTC.58 There were no symptomatic bowel perforations. It is thought that certain patient groups are at increased risk of perforation during CTC, such as patients with acute diverticulitis and those with an acute episode of IBD, where in both conditions, CTC is contraindicated for this reason. Further, the risk is likely increased in patients with a recent colonoscopy with deep biopsy or polypectomy. When comparing the complications of CTC with other screening techniques, the adverse events occurring during subsequent colonoscopy for positive CTC findings should also be included. In a randomised screening trial, CTC and colonoscopy screening resulted in no perforations, but a comparable percentage of postpolypectomy bleedings (0.3% for CTC and 0.2% for colonoscopy).38 The complication rate in FOBT screening was 0.03% (all during follow-up), and in sigmoidoscopy screening 0.08% had a major complication.59

Extracolonic findings

The large majority of extracolonic findings at CTC can be directly classified as non-relevant, obviating further work-up.60–62 In approximately 5%–10% of examinations, additional work-up may be necessary although there is some variation in reporting, most likely related to differences in the definition of important findings.63 ,64 The incidence of extracolonic findings of moderate or high importance at CTC is commonly reported to be approximately 10%–15% of screenees.61 ,65–67 The majority of these findings are moderately important, the proportion of high important findings is in the order of 2%–5%.60 ,62 ,64 ,67 These important findings include approximately 0.5% extracolonic cancers of which renal cell cancer, lung cancer and lymphoma are the most prevalent (figure 4).60 ,62 ,64 ,66 These cancers are mostly not metastasised at the time of diagnosis.66 Further important extracolonic findings include among others, abdominal aortic aneurysms, adrenal masses and non-malignant renal masses. The aforementioned extracolonic findings are incidental findings, but CTC can also be intentionally used for specific extracolonic screening, such as for aortic aneurysms, or be extended to include osteoporosis screening by calculating bone mineral density at CTC.68 ,69 These additional opportunistic screens add value to CTC beyond colorectal evaluation.

Detecting a non-metastatic extracolonic cancer or an aortic aneurysm is a major additional advantage of screening CTC over other screening techniques. This saves lives, reduces burden and prevents costs associated with the treatment of more advanced disease. The downsides are the costs and burden associated with the work-up for ultimately non-relevant findings or findings for which earlier detection does not impact outcome.70 It is not clear which aspect prevails, as empirical data are lacking, but a net benefit from extracolonic assessment might be present. Importantly, when patients and healthcare professionals are asked what they accept as proportion of false positive extracolonic findings at screening CTC to detect extracolonic malignancy, much higher proportion of false positives are accepted than actually occur (at least 99.8% unnecessary imaging tests to detect one additional extracolonic malignancy).71

Cost effectiveness

Whether CTC is useful as a CRC screening test is determined by its clinical efficacy and also by the cost-effectiveness. Two different scenarios are possible: the cost-effectiveness of CTC screening compared with no screening and the cost-effectiveness of CTC screening compared with other screening modalities. Until now, empirical data on the cost-effectiveness of CTC screening are sparse and almost all papers are modelling studies based on presumed costs of CTC screening.

Compared with no screening, CTC has been consistently shown to be cost effective in cost-effective models, as most of the currently available CRC screening tests are.72 These costs associated with CTC screening include the actual costs of the examination itself and also the costs of follow-up examinations, treatment-related costs and the costs for the further evaluation and/or treatment of extracolonic findings. Therefore, CTC at least seems to be an attractive alternative screening test for subjects not willing to undergo other screening options.

When CTC is compared with other screening modalities, it is in most cost-effective models of population-based CTC screening estimated to be less cost effective than alternative screening modalities.73–79 Some of these cost-effective models also indicate that CTC screening could be more cost effective than colonoscopy screening if the unit costs are less than colonoscopy (max 60%–72% of unit costs for colonoscopy) and/or when CTC screening has at least a 25% higher attendance rate.73–76 A recent study showed that the actual average unit costs of CTC screening in a screening programme were around €170 per participant, much lower than the €364–€594 commonly used in cost-effectiveness analysis (based on reimbursement rates for abdominal or pelvic CT, for example), at least for the Dutch situation.80 In combination with the approximately 50% higher attendance rate in The Netherlands of first-round CTC screening compared with colonoscopy, this finding might indicate that CTC screening is a more cost-effective option than colonoscopy screening.38 Of note, some studies have found CTC to be more cost effective than colonoscopy, especially when diminutive lesions are ignored or when extracolonic screening is included.73

Some of the modelling studies on the cost-effectiveness of CTC screening have included or concerned extracolonic findings. Unfortunately, none of these models were based on empirical CTC data and were taking outcome into account as well. There is substantial variation in the average costs reported for the additional work-up of extracolonic findings (ranging from US$2.34 to US$98.56), influenced by the definition of a relevant finding needing work-up, and which costs are included.60 ,61 No studies report on the costs saved by earlier detection of disease, preventing the comparison of the benefit versus drawback of extracolonic findings based on empirical data. Some modelling studies focussed on only one or few extracolonic findings and showed the cost-effectiveness of such an approach, but this does not reflect daily practice where a broad spectrum of extracolonic findings is found.

Ongoing trials

As far as we are aware, at this moment, two randomised controlled trials are ongoing on screening CTC, both in Italy.81 ,82 The first study is being conducted in Florence in Tuscany.81 A total of 14 000 subjects will be randomly invited by mail for CTC (n=5000), colonoscopy (n=1000) or three rounds of biannual FOBT screening (n=8000). Primary endpoints are participation rate, diagnostic yield for advanced neoplasia and average costs per screening technique. The second study is being conducted in the Piedmont region and the Verona district.82 A total of 20 000 subjects aged 58 or 60 years will be invited to participate in screening. Invitees indicating that they are willing to participate, will be randomised for FS or CTC screening, to be able to compare the yield between both tests. An additional 2000 subjects will be randomly invited for CTC or FS to be able to determine differences in participation rate. When a CTC invitee declines the invitation, FOBT will be offered as alternative screening technique. When a FS invitee declines the invitation, FOBT and CTC will be offered as alternative screening techniques.

Future developments

Compared with optical colonoscopy, CTC is a relatively new test for colorectal evaluation. Nonetheless, the techniques and interpretation strategies for CTC are now fairly mature and radical advances are unlikely in the near future. What lies ahead are likely further incremental refinements in areas such as the optimal bowel preparation, preferred distention strategy (eg, using the lateral decubitus position over the prone position), scanning techniques (eg, iterative reconstruction with lower doses), additional software advances and improvement in the CAD algorithms. Adjustments may also be made in terms of the additional clinical indications, such as possibly using intravenous contrast-enhanced CTC for surveillance after CRC resection to combine colonic and extracolonic assessment into a single examination, foregoing colonoscopy. Given the complementary nature of CTC and endoscopy in terms of right versus left colon evaluation, an alternating screening strategy of CTC and sigmoidoscopy seems intriguing. Additional data regarding the natural history of small and diminutive polyps could further bolster the CTC polyp mantra of ‘remove the large, watch the small, and ignore the tiny’. Additionally, data on the performance of CTC for detecting right-sided serrated polyps is expected in the near future (figure 3).

MRI colonography has been proposed as an alternative to CTC largely because of concerns about ionising radiation.83 MRI colonography has been shown to be accurate in detecting large lesions, but for 6–9 mm polyps, data are heterogeneous and largely inferior to CTC.84 In a recent German CTC screening study, good accuracy was reported (per-patient sensitivity for adenomas ≥6 mm 87.1% and specificity 95.3%), demonstrating that good results can be obtained in screening.85 As the radiation dose of CTC has decreased substantially and will further decrease, this advantage of MRI is becoming less important. In addition, costs and availability are drawbacks of MRI colonography that do not make MRI colonography a viable option. A future approach might be molecular-targeted MRI to identify CRC and those adenomas at risk that should be removed while safely ignoring other lesions; this would substantially reduce the need for colonoscopy.

Additional potentially disruptive new technologies for colorectal evaluation will continue to test the current practice paradigms. In particular, the stool DNA test and colon capsule are now emerging as possible new strategies.86 ,87 Even within radiology, both MRI and positron emission tomography are continuing to find new applications for bowel imaging. Last, the near-term role of CTC in colorectal screening within the USA will be heavily influenced by the impending update of screening guidelines by the US Preventive Services Task Force. An ‘A’ or ‘B’ grade for CTC screening by this body would likely lead to coverage for Medicare beneficiaries and be viable as a screening test in general.

Role of CTC in organised population screening

In the European Union, CRC screening primarily concerns organised population-based screening, and here, the stringent assessment of a potential screening test concerns many aspects including cost-effectiveness. In 2010, the European Union Committee on cancer published a report on primary population-based CRC screening and stated that CTC should not be used for primary screening before it has been demonstrated to be consistently sensitive and that the technique is established (including cut-off for referral, costs/cost-effectiveness and risk of radiation exposure).1 Several of these important aspects have been addressed in the intervening years, which make CTC a potential viable option for population-based CRC screening. However, the cost-effectiveness of CTC is still an open question. For that reason, in a 2014 consensus document, the European Society of Gastrointestinal Endoscopy (ESGE) and the ESGAR at this stage do not recommend CTC for primary screening. However, on an individual basis, it may be used for screening.2

In several European countries, population-based colorectal screening programmes are ongoing or being rolled out. As far as we are aware, primary CTC screening is not used in Europe. In countries like Germany and Spain, primary colonoscopy screening is offered, while primary FOBT or FIT screening is being used in countries like Italy, UK, the Netherlands and France.88 In case of a FOBT or FIT positive result, CTC is a good alternative for colonoscopy when contraindicated or when the invitee refuses colonoscopy as follow-up examination as also recommended in the ESGE/ESGAR consensus document.89 Recently, a review was published on the estimated sensitivity and specificity of CTC for advanced neoplasia in FOBT positives.90 This review included data of five different studies, a total of 622 patients. The average per-patient sensitivity was 89% for adenomas of 6 mm and larger, and CRCs. Retrospective analysis of routinely coded data in the English Bowel Cancer Screening Programme showed that the overall detection rate of CTC for advanced neoplasia was 19% in 2731 guaiac FOBT positives, while colonoscopy detected advanced neoplasia in 33% of 72 817 screening positives undergoing colonoscopies.34 However, CTC could also be a useful additional screening technique in countries offering colonoscopy as primary screening technique. This is illustrated by the results of the few screening programmes at centres of excellence within the USA. Within a large academic tertiary care facility in the USA, the attendance rate at CRC screening has increased significantly after the introduction of CTC as an alternative screening technique for colonoscopy screening in 2004.91

Conclusions

CTC has a comparable sensitivity for CRC to colonoscopy and also a comparable or slightly lower sensitivity for advanced neoplasia. As other screening programmes that employ tests that are much less accurate in the detection of adenomas and cancers have shown reductions in CRC-related mortality, it is reasonable to assume that the use of CTC in screening will lead to an even larger reduction in CRC-related mortality, provided that a substantial proportion of individuals participate. Overall, screenees prefer CTC over colonoscopy screening with a higher participation rate than for colonoscopy screening. Although radiation exposure is a potential drawback, this disadvantage is overemphasised, especially with newer technology. At this time-point, it is not entirely clear whether the detection of extracolonic findings at CTC is of net benefit and is cost effective, but with responsible handling, this may be the case. Future efforts will seek to further improve the technique, refine appropriate diagnostic algorithms and study cost-effectiveness.

References

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Footnotes

  • Contributors All authors were responsible for writing the manuscript.

  • Competing interests PJP is co-founder of VirtuoCTC and shareholder in Cellectar Biosciences.

  • Provenance and peer review Commissioned; externally peer reviewed.

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