Computed tomography colonography vs. colonoscopy for colorectal cancer screening: close call, but not closed case

Computed tomography colonography (CTC) has been proposed as an alternative to colonoscopy in colorectal cancer (CRC) screening [1]. CTC is less invasive than colonoscopy and therefore it has been argued that CTC would inflict fewer complications and be less of a burden to patients, leading to better patient acceptance compared with colonoscopy [2].

In this issue of Endoscopy, van Dam et al. report on an important add-on study of the COCOS (Colonoscopy or CT Colonography for Screening) trial, the first large, multicenter randomized controlled trial comparing non-cathartic CTC with colonoscopy for CRC screening [3] [4]. Van Dam’s detailed diary study was motivated by the recognition that as well as pain and discomfort during the procedure, the burden during the whole screening process (defined as the time interval from start of bowel preparation until returning to normal life [“feeling normal again”] after screening) is an important barrier to screening participation. As the study shows, individuals who underwent colonoscopy reported a longer time required for the appointment itself, chiefly because of the time for recovery after sedation; however, individuals who underwent CTC experienced a significantly longer time for the whole screening process until “feeling normal again” (median 43 hours vs. 35 hours; P < 0.001). Post-examination side effects were comparable for the two methods, except for abdominal complaints, which were more common after CTC compared with colonoscopy (85 % vs. 52 %; P < 0.001).

The van Dam study, together with the other recent reports from the COCOS trial, has advanced our knowledge of CTC for CRC screening significantly [3] [4] [5]. Colonoscopy detects more advanced lesions per participant than CTC, but better compliance with (non-cathartic) CTC outweighs the diagnostic superiority of colonoscopy, resulting in comparable yield in an intention-to-screen approach [4]. With regard to side effects, the overall burden of participation in screening is probably very similar between colonoscopy and CTC, with shorter appointment times for CTC but longer-lasting post-procedural abdominal complaints compared with colonoscopy [3]. In summary, therefore, one may conclude that there is no large difference in patient burden between colonoscopy and CTC. Finally, the COCOS trial also showed that there is no difference in complication rates between CTC (0.3 % serious adverse events) and colonoscopy (0.2 %) when comparing the two screening paths including therapeutic polypectomies after CTC in the CTC group (which is the most reasonable approach to assessing this topic) [4]. CRC screening target populations should therefore be rigorously informed about their choices of screening tools, with detailed information on expected burden and inconveniences, complication rates, and expected yield of the different options. Importantly, this information should be given using absolute numbers for disease risk, yield, burden and complications. For example, leaflets should not say “Colonoscopy may reduce CRC incidence by 50 %,” but “Your 10-year risk of getting CRC is 1 % without colonoscopy; and colonoscopy may reduce this risk to 0.5 %” [6].

The COCOS trial is a remarkable example of high-quality clinical research answering burning questions in endoscopy and CRC screening. Hallmarks of the success of the Dutch model are close co-operation between endoscopy environments at major academic clinical centers and, importantly, excellent interaction with world-class expertise in clinical epidemiology, database management, and biostatistics. This results in a sound trial design and powerful trial machinery, covering the whole process from the conception of the trial, over recruitment and data analysis, to publication and (hopefully) implementation in clinical practice.

Does the COCOS trial answer all the “big” questions we have with regard to CTC? No, it does not, because the trial does not address the overarching question of the effectiveness of CTC in reducing incidence and death from CRC compared with other screening tools. Although the design of the trial and the availability of the Dutch healthcare registries would permit follow-up of participants for the next 10 – 15 years in order to establish these most important endpoints, COCOS (although a very large clinical trial with more than 8800 participants) is unfortunately not large enough to provide definitive answers on the magnitude of CRC incidence and mortality reduction after CTC vs. colonoscopy screening.

• References

• 1 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. CA Cancer J Clin 2008; 58: 130-160
• 2 Pickhardt PJ. Strong evidence in support for CT colonography screening. Lancet Oncol 2012; 13: 6-7
• 3 van Dam L, de Wijkerslooth T, de Haan M et al. Time requirements and health effects of participation in colorectal cancer screening with colonoscopy or computed tomography colonography in a randomized controlled trial. Endoscopy 2013; 45: 182-188
• 4 Stoop EM, de Haan MC, de Wijkerslooth TR et al. Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: a randomised controlled trial. Lancet Oncol 2012; 13: 55-64
• 5 de Wijkerslooth TR, de Haan MC, Stoop EM et al. Reasons for participation and nonparticipation in colorectal cancer screening: a randomized trial of colonoscopy and CT colonography. Am J Gastroenterol 2012; 107: 1777-1783
• 6 The Lancet Editors. The trouble with screening. Lancet 2009; 373: 1223