CT colonography: does it satisfy the necessary criteria for a colorectal screening test?

Abstract

Existing and emerging colorectal screening tests can be assessed in terms of the key categories of diagnostic performance, procedural risks, patient acceptability, and cost-effectiveness. To push a new screening test to acceptance, it need not outperform existing strategies in all of these criteria. Rather, a relative advantage in one criterion combined with acceptable performance in the others may be considered adequate. For computed tomographic colonography (CTC), a strong case can be made that this test meets or exceeds optical colonoscopy, the current screening standard, in all of these categories. Published data, including our own experience with CTC screening, will be reviewed to support this claim. Reasons why CTC has not yet achieved its full potential as a valuable screening test for colorectal cancer prevention will also be considered.

Keywords::

• colonoscopy
• colorectal cancer
• colorectal polyps
• CT colonography
• screening
• virtual colonoscopy

Colorectal cancer is a preventable condition that remains the second leading cause of cancer death throughout the developed world, primarily because many adults are not properly screened. It is clear that additional effective yet more acceptable screening options are needed to improve adherence rates. Computed tomographic colonography (CTC) represents an emerging screening test with great promise to address this gap. In an editorial responding to early CTC data published back in 2003 (before publication of the Department of Defense screening trial), Rex [1] outlined a number of key criteria to consider when comparing colorectal screening tests: diagnostic performance, procedural risks, patient acceptability and cost–effectiveness. Although he noted that a new test did not necessarily have to outperform existing strategies in all or even any of these criteria to be accepted, he concluded (based on the limited available data at the time) that it was too early to endorse CTC for screening or surveillance. Now that a full decade of experience has passed since that assessment, including many clinical trials and small clusters of early adoption, how does CTC currently stack up as a colorectal screening test? What follows is a brief review of the interval CTC data relevant to the four key categories outlined above.

In terms of diagnostic performance, CTC has repeatedly shown high sensitivity for clinically relevant polyps in well-designed trials, either comparable or superior to optical colonoscopy [2–4]. Overall sensitivity for colorectal cancer with CTC may even exceed that of optical colonoscopy, presumably due in part to improved detection of right-sided lesions [5]. High specificity seen in the clinical trial setting has translated into high positive predictive values in clinical practice [6]. The yield for advanced neoplasia at routine CTC screening in clinical practice has also been shown to be equivalent to that of primary optical colonoscopy, despite the fact that fewer than 10% of CTC cases are subjected to polypectomy [7]. In vivo CTC surveillance of small 6–9 mm polyps appears to be a powerful biomarker by selectively identifying lesions of clinical significance through interval growth, thus reducing the number of invasive colonoscopies [8]. Ignoring isolated diminutive lesions at CTC not only improves its overall cost–effectiveness (see below), but there also appears to be an overall reduced interval cancer rate 5 years out from a negative CTC compared with that seen after negative colonoscopy [9]. This is presumably due to increased initial detection of advanced neoplasia at CTC screening relative to colonoscopy screening. CTC is also quite effective for detecting clinically relevant flat lesions, despite a common misperception to the contrary [10]. One legitimate concern regarding the potential widespread use of CTC is whether the results seen at centers of excellence can be duplicated at the community level. Similar quality issues apply to colonoscopy.

CTC is a minimally invasive examination with an extremely low complication rate. Unlike optical colonoscopy, the risk of perforation at CTC screening approaches zero [7,11]. To date, we have yet to encounter any significant complication in our CTC program. CTC also avoids the more common procedural risks of bleeding and sedation-related events often observed at colonoscopy. The CTC screening paradigm appropriately reserves colonoscopy for true therapy (polypectomy), where the risks of this invasive test are more acceptable compared with asymptomatic screening (i.e., no a priori knowledge of important lesions).

Patient acceptance of colorectal screening tests is closely linked to adherence and compliance rates. Among the published survey studies, the vast majority show a strong patient preference for CTC over colonoscopy [12,13], despite the fact that no pain control or sedation is provided at CTC. Beyond the avoidance of needles and intravenous medications, additional advantages of CTC screening include the ability to drive oneself home after the procedure, immediate return to regular activities, evaluation of extracolonic structures and avoidance of complications. Non-cathartic approaches to CTC may further improve adherence but trade-offs exist with this approach. Overall, basic safety is a cardinal tenet of any population-based screening examination.

Cost–effectiveness analyses are complex and require an extensive review of the specific model and inputs to ensure valid results [14]. Not surprisingly, one can often find a cost–effectiveness study that generally supports whatever claim is being defended. Having said that, it stands to reason that primary CTC with selective polypectomy should be more cost-effective than primary colonoscopy if certain basic assumptions are met. One key assumption that is often missed is that polypectomy should be avoided for isolated diminutive lesions seen at CTC [15]. Diagnostic performance for CTC should reflect current practice and the input cost for CTC should be considerably less than colonoscopy. Ideally, extracolonic assessment should be factored in as well [16]. In general, it is quite easy to demonstrate that CTC is cost-effective compared with no screening [14], but with realistic input assumptions it can also be shown to be much more cost-effective than endoscopic strategies [15,16]. Beyond the typical Markov modeling, other decision analyses have been applied to certain key aspects of CTC screening, such as the management of small (6–9 mm) polyps [17,18].

It is clear from the above discussion that CTC not only satisfies the basic criteria for a colorectal screening test, but matches or outperforms optical colonoscopy in all of these categories. Based on these facts, as well as my own clinical experience over the past decade, I maintain the mantra that CTC is ‘better, faster, safer and cheaper’ than optical colonoscopy for colorectal cancer screening. Despite the overwhelming data in support of CTC screening, clinical implementation continues to lag far behind the endoscopic- and stool-based colorectal screening tests. In my opinion, this disconnect has little to do with science or reason but simply reflects certain realities and current shortcomings of our healthcare system. The status quo is left unaltered by an unfortunate yet unforgivable combination of income preservation instinct, misinformation, lack of awareness by the public, bureaucratic inertia and politics as usual. Perhaps by clinging to an idealistic notion that truth and justice might still prevail, I continue to believe that CTC screening will eventually assume its rightful place among the colorectal cancer screening options.

Although the case for widespread implementation of CTC screening in the USA was quite strong 5 years ago, particularly following the endorsement by the American Cancer Society and the major gastrointestinal societies [19], facts and good intentions alone do not guarantee success. As long as screening colonoscopy continues to account for a major source of income for gastroenterologists, the resulting protection of ‘turf’ may continue to be insurmountable for CTC in the near term. However, there is a growing awareness of the exorbitant cost of primary colonoscopy screening among policy makers, insurers and the public at large. Furthermore, in the midst of US healthcare reform that seeks to improve efficiency and cost–effectiveness, a test that simultaneously screens for colorectal cancer, other cancers, abdominal aortic aneurysm and osteoporosis, among other things, should be quite appealing [16,20].

From a practical standpoint, the following concrete steps are likely necessary to establish a realistic pathway for widespread implementation of CTC screening to benefit the population. An ‘A’ or ‘B’ grade from the US Preventive Services Task Force resulting from its impending re-assessment of CTC screening would likely result in a reversal of the previous negative coverage determination by the Centers for Medicare and Medicaid Services for its Medicare beneficiaries. The recent endorsement of CTC screening by the US FDA Medical Devices Advisory Committee that convened in September 2013 might have a positive influence on these upcoming deliberations. An alternate pathway to Medicare coverage for CTC screening would be passage of the bills currently sitting in the US Senate and House of Representatives, which was the path taken by optical colonoscopy over a decade ago. Regardless of the precise route, Medicare coverage would then presumably give rise to widespread coverage of CTC screening by other third-party payers. It is the younger screening cohort in the 50–64 year-old age range that would likely benefit most from access to CTC.

Lacking a crystal ball for prognostication, the potential for widespread coverage of CTC screening within the next 1–2 years nonetheless appears brighter than it did just a year ago. Emerging evidence suggests that stool DNA and other stool-based screening strategies remain relatively insensitive for advanced adenomas, resulting in a lack of cancer prevention that makes both optical and virtual colonoscopy much more attractive. As such, CTC continues to be the most promising of the emerging screening tools but remains grossly underutilized at the time of this writing.

Financial & competing interests disclosure

PJ Pickhardt has served as a consultant for Midways, Braintree, Viatronix and Check-Cap; and is co-founder of VirtuoCTC. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.