A study led by a BRC-funded researcher has found that a new, less invasive diagnostic test is significantly more sensitive for colon cancer than the current radiological standard of barium enema and not significantly different from the ‘gold-standard’ of colonoscopy.
Currently, the standard procedures for diagnosis of symptomatic colon cancer are colonoscopy and barium enema. Computed tomographic colonography (CTC) is a newer procedure during which a CT scanner takes images of the colon, which are subsequently rendered in 3D thereby simulating colonoscopy – hence the alternative term “virtual colonoscopy”.
Unlike colonoscopy, where a flexible endoscope is passed along the large bowel, CTC is minimally invasive and does not require sedation.
BRC-funded researcher Professor Steve Halligan and colleagues from UCL, Imperial College and Birmingham University carried out a multicentre pragmatic randomised trial on over 5,000 patients with symptoms potentially suggestive of colorectal cancer. Steve Halligan is Professor of gastrointestinal radiology at UCL and led the radiological aspects of the trial while his co-principal investigator, Wendy Atkin, Professor of gastrointestinal epidemiology at Imperial College, was responsible for recruitment, data collection and analysis.
Patients aged 55 years or older were recruited from 21 NHS hospitals. Because patients believed suitable for colonoscopy are not equivalent to patients believed suitable for barium enema, two parallel trials were performed, one comparing CTC to barium enema and one comparing CTC to colonoscopy. The pragmatic design allowed the researchers to observe the effect of procedures exactly as would happen in day-to-day clinical practice. The trials were funded predominantly by the National Institute for Health Research (NIHR) Health Technology Assessment Programme.
The two trials, published back-to-back in the Lancet, found that CTC was significantly superior to barium enema for diagnosis of colorectal cancer and large polyps (the precursor to cancer), and follow-up of patients for several years after randomisation found that CTC missed fewer cancers. In the other trial, there was no significant difference between CTC and colonoscopy for diagnosis (11% for both procedures) but additional colonic investigation was required after CTC in approximately 30% of patients, mostly to confirm suspected diagnoses (often small and clinically insignificant polyps). The corresponding rate for colonoscopy was approximately 8%.
The researchers concluded that CTC should replace barium enema (over 70,000 of which were done last year in England alone) and that CTC was a viable but less invasive alternative to colonoscopy. However, because rates of additional investigation were substantially higher following CTC than colonoscopy, they concluded that guidelines for reporting radiologists are needed to reduce the referral rate after CTC.
A perceived benefit of CTC, both by medical practitioners and patients, is its ability to image organs outside the colon, which might be the source of symptoms. The researchers found that approximately two-thirds of patients had extracolonic “abnormalities” found on CTC. Overall, 10% of patients having CTC underwent additional tests to clarify the importance of such findings; a cancer was diagnosed in approximately 2% overall. The authors state that further research is needed to determine whether the ability of CTC to image extracolonic organs is ultimately beneficial.
Psychological investigations were led by Dr Christian von Wagner, senior research associate in the health behaviour unit at UCL. He found that patient experience of CTC compared favourably to both barium enema and colonoscopy. An economic analysis led by researchers at Birmingham found CTC cost-effective when compared to barium enema and equivalent to colonoscopy.
Despite the benefits of CTC, it is not for everyone. Patients with a history of inflammatory bowel disease, such as ulcerative colitis or Crohn’s, were diagnosed significantly more frequently by colonoscopy.
This study is an example of how BRC experimental medicine activity leads on to later phase clinical trials carried out in large populations. The BRC is committed to the development of new therapies and diagnostics in colorectal cancer as part of our BRC strategy.
Additional support for the trials was provided by the NIHR Biomedical Research Centres funding scheme, Cancer Research UK, and the EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare. Medicsight, Viatronix, Bracco UK Ltd, and Barco provided equipment.
Pragmatic RCTs: In general, there are two types of random controlled trial (RCT), “pragmatic” and “exploratory”. The aim of an exploratory RCT is to determine whether a new treatment or procedure works in ideal circumstances. For example, exploratory trials are often performed in subjects that have been highly selected for the disease/condition in question, and are performed in relatively few centres by highly-trained researchers. In contrast, a pragmatic RCT is one where the new intervention is tested under conditions that are more typical of normal day-to-day practice. The treatment or intervention is usually already being used in clinical practice, the practitioners and patients are less highly selected than for exploratory RCTs, and the number of centres is often larger.
