Several organizations have raised concerns about the radiation risks from CT colonography screening and requested additional research be conducted in this area (3
). We used updated risk projections models and microsimulation models to estimate the benefit-risk ratio for radiation risks from repeated CT colonography screening. The benefits from screening every five years age 50-80 were estimated to clearly outweigh the radiation-related cancer risks. Inclusion of the radiation-related risk from CT scans used to follow-up extracolonic findings did not materially alter these findings.
We used the National CT Colonography trial protocol (7
) to estimate the mean effective dose estimates associated with CT colonongraphy and the sensitivity of CT colonography was also based on the results from this trial, ensuring directly comparable estimation of benefits and risks. The protocols should also be reasonably representative of current screening practice in the US since the trial included a variety of community and academic sites using 16+ slice multi-detector CT scanners (1
). Our dose estimates were also similar to the mean dose for the US in a recent review of international CT colonography screening protocols (7-8mSv versus 6.7mSv) (21
) and in line with recent recommendations by the American College of Radiology (23
). Variation in doses across scanner types (Appendix 2
) is likely due to differences in x-ray beam intensity and beam spectrum (24
). It has been suggested that radiation doses from CT colonography could be reduced further (25
). However, to date these low-dose protocols do not seem to have been widely adopted, possibly due to a reluctance to accept lower image quality.
A previous radiation risk projection study by Brenner and Georgsson estimated that the risk of radiation-related cancer from CT colonography screening was more than two-fold higher than our mean estimate (0.14% for a single screen at age 50 compared to 0.06%) (6
). Our organ-specific dose estimates were broadly similar to those used by Brenner and Georgsson. The differences between the risk estimates are due primarily to different assumptions regarding risk transfer from the Japanese to the US population in the recent BEIR VII report (used here) compared to the previous BEIR V report (used by Brenner and Georgsson) (7
). Detailed discussion of these assumptions is beyond the scope of this paper but is covered in detail in the BEIR VII report (7
). The upper uncertainty bounds for our radiation risk estimates correspond (approximately) to the assumptions in the BEIR V report. Even using the upper uncertainty bounds of the risk estimates the benefit-risk ratio was 4:1 or higher for screening from age 50-80. A recent cost-effectiveness analysis for CT colonography screening (28
) incorporated these earlier radiation risk estimates (6
). Unfortunately the estimate of lifetime cancer risk used was incorrect by a factor of ten (0.01% instead of 0.1%). No other published studies have provided the information in the form necessary to conduct a direct comparison of the radiation risks and benefits from repeated CT colonography screening.
A number of studies have shown that 5-10% of asymptomatic screening patients will have a clinically significant extracolonic finding on CT colonography screening (16
). There are potential benefits from these findings such as the visualization of abdominal aortic aneurysms (29
) but there are also additional risks, including an additional risk of radiation-related cancer from follow-up CT scans. We were only able to conduct crude calculations for these follow-up scans due to limited available data. In particular we had no data on the follow-up of extracolonic findings after the first screening round, which may be lower if previously observed findings are not referred for additional follow-up. Despite our probable over-estimation of the risks associated with follow-up scans, our results suggest that the additional radiation risk from these scans is unlikely to significantly alter the overall benefit-risk ratio.
Very large studies with lifelong follow-up would be required to accurately and directly quantify risks from low-dose radiation exposures like CT colonography screening (5
), which is why we used an indirect modeling approach to provide a more timely estimate of the potential risks based on existing data. There is an ongoing scientific debate about the linear no-threshold assumption, which forms the basis for these risk projections (29
). This assumption is that there is no dose below which there is no risk of radiation-related cancer and that the risk at low doses is approximately linear. Most national and international radiation protection organizations support the use of this assumption for the purpose of radiation protection (7
). Although there is evidence of excess cancer risks from low-dose exposures in studies of the Japanese atomic bomb survivors, nuclear workers and patients exposed to multiple diagnostic X-rays (7
) many uncertainties remain including the magnitude of the effects at low doses and the effects of single acute exposures compared to fractionated exposures or protracted exposures. Risk projection methods can help to quantify the potential risk, but because of the uncertainties these methods require a number of assumptions.
An important strength of our study was the use of Monte Carlo simulation methods to quantify the uncertainties in the radiation risk estimates ; this allowed us to examine the benefit-risk ratio at the extremes of the radiation risk limits. However, there are other uncertainties and assumptions involved in such risk projections that were not included in the uncertainty intervals, such as uncertainty about the biological effectiveness of low energy X-rays in terms of cancer induction. We assumed that they are equally effective as higher energy gamma rays, the primary exposure from the Japanese atomic bombs. It is possible that they may be more carcinogenic, which would mean that our projections would under-estimate the cancer risks, possibly by a factor of two (7
). A possible source of over-estimation of the risks is that some colorectal cancers that are related to the radiation from the CT colonography screening may be detected at future screening rounds. Furthermore, our results assume screening is performed every 5 years; some recent guidelines suggest that it could be conducted every 10 years (32
). This would reduce the radiation risks presented here by approximately 50%.
No direct estimates of the colorectal cancer incidence or mortality reductions from CT colonography screening are currently available. To date the randomized trials have only assessed surrogate markers for efficacy, primarily screening sensitivity (1
). Our estimates of the number of colorectal cancers prevented by screening varied between the three microsimulation models primarily because of the differences in the assumed dwell time (the amount of time between onset of an adenoma and clinical presentation of colorectal cancer). The comparative modelling was another strength of the current study, and despite differences in estimated disease reduction, the conclusions were qualitatively similar for all three models. These analyses provide a plausible range for expected results, but do not provide information about the precision of the estimated benefit of CT colonography. The uncertainty limits for estimated benefit:risk ratios only account for uncertainty in the estimated risk, and therefore underestimate the overall uncertainty of this ratio.
It is unlikely that there will be direct estimates of either the radiation risks or the number of cancers prevented by CT colonography screening in the near future. In the absence of direct evidence, this modelling approach, which was based on the best available current data, suggests that after age 50 the benefits clearly outweigh the radiation risks from CT colonography screening. The estimated risk of radiation-related cancer per screen is small, <0.1%, especially when compared to the typical background lifetime risk of developing cancer of about 40% (33
). Screening is not generally recommended for the general population before age 50 (2
), and our results suggest that the absolute benefit may not be much greater than the radiation risk for screening age 40-49. Our estimates can be used to help inform the overall risk-benefit assessment of CT colonography in comparison with alternative colorectal cancer screening options.