Abdominal symptoms are often vague and the organ of origin may be obscure, often beyond the colorectum. Therefore, the ability to interrogate structures outside the gastrointestinal tract at the same time as a high-quality examination of the colorectum may be advantageous for symptomatic patients. Furthermore, it may permit serendipitous discovery of unrelated (but clinically-important) pathology. Conversely, extracolonic detection may be a disadvantage if it precipitates further tests (with the associated costs, inconvenience and risks that these entail) for incidental findings that transpire to be of no clinical importance ultimately. CTC is readily able to depict extracolonic pathology in the torso from the lower chest to the bottom of the pelvis, since CT scanning of this region is a fundamental requirement of the technique (Fig. 5.3). Conversely, colonoscopy rarely detects extracolonic disease unless it spreads directly into the colon (for example, extrinsic involvement by serosal tumour, typically arising from the gynaecological tract; or by endometriosis) or involves it as part of a multiorgan process (e.g. vasculitis or amyloidosis), and rarely even then. In a symptomatic setting, where the colon is normal, the patient still has a problem that caused them to seek medical attention, and, at least in some cases, the next step would be to investigate the other abdominopelvic viscera, and CTC neatly combines these aspects in a single examination.

Although seemingly intuitive, this approach is not necessarily of clinical benefit. Not all symptoms or signs suggestive of CRC require extracolonic evaluation if colorectal investigation has been negative. Genuine bright red rectal bleeding is very rarely due to extracolonic pathology; iron-deficiency anaemia should initially provoke assessment of the upper gastrointestinal tract rather than the other abdominopelvic viscera; and so on. Although observational data provide some useful information confirming that CTC can and indeed does depict extracolonic pathology, including neoplasia [32], the clinical trajectory of such diagnoses in comparison to the default (colonoscopy) is largely unknown with such study designs, particularly for symptomatic patients. Randomized data from the paired SIGGAR trials [33] help address this issue, since this avoids the biases inherent to other designs.

Taken together, at least one previously unknown extracolonic finding was diagnosed by CTC in 959 (58.7%) of 1634 patients (excluding those patients with CRC). For the most part, extracolonic findings were unimportant, and did not merit further diagnostic investigation. However, 136 (8.3%) patients having CTC ultimately did have an extracolonic finding investigated (or treated); approximately half of these investigations were non-invasive imaging only, with the remaining half being an invasive procedure or surgery (with a roughly equal split between the two). Surgery was sometimes to combine treatment with diagnosis (for example, excision biopsy); the commonest surgical procedures were nephrectomy, oophorectomy (with or without hysterectomy) and aneurysm repair. Extracolonic diagnosis were judged to explain the patient’s presenting symptoms in only 3–4% of patients overall. Ultimately, 25 patients (1.5%) having CTC were diagnosed with extracolonic malignancy. Conversely, no patients undergoing colonoscopy required evaluation for extracolonic pathology, and only 42 of 2223 patients (1.9%) having barium enema had one or more extracolonic finding reported. Five patients (0.2% of the total) ultimately received an extracolonic diagnosis, of which three were malignant. A further 14 patients having CTC had aortic aneurysms diagnosed, compared to none for barium enema or colonoscopy.

At first sight, therefore, this appears to be a clear benefit for CTC—1.5% of patients having CTC received a diagnosis of extracolonic malignancy, compared with 0.13% for barium enema and none for colonoscopy. However, this difference was short-lived; by 1 year, using cancer registry data, there was no difference in the diagnosis rates of extracolonic malignancy irrespective of the initial randomized procedure. This is surprising—how are patients having barium enema or colonoscopy receiving a diagnosis of extracolonic malignancy? There are several possible explanations; firstly, not all malignancies can be diagnosed by CTC—early cross-sectional abdominopelvic imaging can only ever affect diagnosis rates for certain primary tumours (particularly renal, ovarian and pancreatic). Since the commonest malignancies are those of the lung, breast and prostate, none of which are readily diagnosed by CTC, it is implausible that CTC accelerates their diagnosis, diluting the effect of early CT. Indeed, in the SIGGAR trials, 58% of cancers diagnosed within 1 year of randomization to CTC had not been diagnosed by CTC itself; either because they were outside of the field of scanning or were occult (or overlooked) at that time. Secondly, and perhaps most pertinent, it is highly probable that patients randomized to barium enema or colonoscopy underwent cross-sectional imaging subsequently as the search for the cause of their symptoms continued. As noted above, even after normal colonic investigation, patients may still have symptoms, provoking their physician to investigate further. This is with good reason—incidence rates of extracolonic malignancy in the SIGGAR trials were double that of the general population (matched for age and sex)—abdominal symptoms are clearly an important flag and further investigation is warranted.

Therefore, although CTC permits rapid diagnosis of some extracolonic malignancies, there is no difference in the rate of such diagnoses by 1 year, when compared with colonoscopy. It is likely that this is partly because some cancers are not diagnosable by CTC, and partly because colonoscopy is often followed up by additional abdominopelvic cross-sectional imaging (namely CT). This has considerable implications for the cost-effectiveness of the two tests, and it is to this aspect that we turn next.

Most studies of the cost-effectiveness of CTC have described models rather than actual data observed in a trial. Furthermore, most models have compared the cost effectiveness of CTC versus alternatives in a screening context. The situation for symptomatic patients is different—prevalence of both colonic and extracolonic abnormality is much higher, implying that CTC is far more likely to be followed by confirmatory or therapeutic colonoscopy in a symptomatic setting versus screening. The goals of investigation are also rather different. Screening aims to (a) reduce CRC incidence (by prophylactic polypectomy, thereby interrupting the adenoma-carcinoma or serrated pathways to carcinogenesis) and (b) decrease CRC mortality by early detection, thereby increasing the likelihood of curative treatment. The cost-effectiveness of screening is largely contingent on improving these outcomes and may even be cost-saving because disease becomes less common, and is easier and cheaper to treat if it does occur. Conversely, investigation of symptomatic patients aims to explain symptoms and exclude serious causes. By the time CRC is symptomatic, it is on average more advanced than CRC detected by screening; and disease prevention is less effective because patients are typically older and have more co-morbidity, meaning they may not have sufficient life expectancy to benefit from prophylactic polypectomy. Accordingly, symptomatic and screening scenarios require separate cost-effectiveness models.

Clearly, such models are highly dependent on the inputs, which include estimates for the frequency of tests (which depend on study setting and healthcare systems from which they are derived) and their unit costs. Unit costs of both CTC and colonoscopy vary widely internationally, as do the downstream trajectory and costs of future clinical activity (e.g. further tests, outpatient attendances, surgical procedures, hospitalization etc.). Most models have utilized estimates drawn from a wide range of primary research and so these estimates differ widely. However, it is well-recognised that the most accurate models use estimates drawn directly from observations obtained directly from a pragmatic clinical trial, since these best reflect what happens in “real life”. Again, the most robust data to date are from the SIGGAR trials, which were pragmatic (i.e. designed to be representative of routine clinical practice), included a range of differing hospitals (21 in total), and health economic data were collected prospectively with the intention of a cost-effectiveness analysis. The results were surprising: Although the unit cost of CTC is considerably lower than that for colonoscopy (and subsequent testing was far higher for patients randomized to CTC), once downstream costs were considered, the difference between the two tests virtually disappears; total costs were £651 per patient for colonoscopy and £627 for CTC, a difference that was not statistically significant. Since referral rates for colonoscopy after CTC was a surprisingly high 30%, costs would move further in favor of CTC if referrals could be decreased. Additionally, for CTC specifically, roughly half of the overall per-patient costs were due to downstream costs (primarily, confirmatory colonoscopy or investigation of extracolonic findings). Since colonoscopy did not precipitate any immediate extracolonic investigation, downstream costs were much lower. However, the preceding section makes it clear that patients having colonoscopy are very likely having CT scanning or similar within 1 year of initial referral, representing costs that were not captured in the original trial data: costs beyond the immediate diagnostic episode were not captured. If true, this will increase the downstream costs of colonoscopy very considerably, and so reduce its cost-effectiveness relative to CTC.