Colonoscopy is a well-accepted strategy for prevention of colorectal cancer death (52
) and efforts to promote its use have increased the proportion of Americans who report having had the procedure (7
). However, the value of alternative rescreening strategies for those with a negative initial exam is uncertain. Ideally, a randomized trial would address this question, but such a study is unlikely to be performed. Results from a validated simulation model can therefore be informative.
Since it is debatable whether policy decisions and clinical recommendations should be informed by analyses that assume perfect adherence or those that incorporate more realistic, but poorly-described imperfect adherence rates, we evaluated both adherence scenarios. Notably, conclusions were similar across scenarios. Compared with the currently-recommended strategy of continuing ten-yearly colonoscopy after an initial negative exam, all of the other rescreening options we examined provide approximately the same benefit in life-years with fewer complications and at a lower cost. Therefore it is reasonable to rescreen individuals with a negative colonoscopy with other modalities.
Our findings have several implications. Colonoscopy has become the accepted standard for colorectal cancer screening in the US. However, there are not enough trained colonoscopists to perform all of the necessary screening procedures. Using modalities other than colonoscopy for rescreening may help to solve this shortage as it would free up scarce colonoscopy personnel to perform more primary screening exams.
From a policy perspective, the potential cost-savings (in 2010 dollars) from switching to FIT or HSFOBT following a negative screening colonoscopy rather than continuing colonoscopy are considerable. For every individual who switches, $450 to $495 is saved over their lifetime (assuming imperfect adherence). Data from the 2008 National Health Information Survey (53
) indicate that approximately 40% of 50–54-year-olds had an endoscopy within the recommended intervals, and 92% reported their most recent endoscopy was a colonoscopy. On average, no adenomas or colorectal cancer are detected in 82% of initial screening colonoscopies (39
). This suggests that if the estimated 6.6M 50–54-year-olds who had a negative screening colonoscopy in 2008 (that is, 40% × 92% × 82% × 21.5M 50–54-year-olds (54
)) were rescreened with yearly FIT or yearly HSFOBT, $3 billion could be saved over the course of their lives. The cost-savings from switching to five-yearly CTC following a negative colonoscopy are lower yet still sizable ($0.6 billion), although these savings could be at least partially offset by the costs of working up extracolonic findings.
Our analysis has a number of limitations. We did not consider the risks and costs of radiation exposure from CTC because the radiation-related cancer risk was estimated to be very small in comparison to the reduction in colorectal cancer risk from CTC screening (55
). We also did not include the risks, potential benefits, or costs associated with the detection of incidental findings by CTC. The prevalence of clinically-significant incidental findings in asymptomatic populations ranges from 7% to 11%, and the average cost of their work-up (in US settings) has been estimated at $28 to $99 per person screened (56
). When these costs, as well as any potential cost-savings (and gains in life-expectancy) associated with earlier detection of clinically-significant disease are confirmed, they should be included in the assessment of a CTC strategy.
Data from several studies suggest that colonoscopy may not offer as much protection from right-sided compared with left-sided disease (19
). We did not incorporate this into our analysis because the reasons for the difference remain unclear, but likely involve a combination of technical and biological factors that may affect the location-specific effectiveness of colonoscopy as well as other screening modalities. When additional data become available that confirm the magnitude of the effect and elucidate the mechanism, they should be incorporated into an assessment of all modalities.
There are limited data on test-specific adherence, particularly among those who already had a colonoscopy and had no adenomas or colorectal cancers detected. Imperiale (39
) reported adherence of 52% with a repeat colonoscopy five years after a negative exam. It is unclear if adherence ten years after a negative colonoscopy would differ. In the absence of data for CTC, we assumed adherence with the first CTC was equal to that with a repeat colonoscopy (that is, 52%) and that individuals on average have two CTCs by age 75. Many have suggested that adherence with CTC for initial screening may be higher than with colonoscopy (60
), although such claims have been based on small single-institution studies. A Dutch population-based study found that screening uptake was higher for CTC vs. colonoscopy (63
). However, CTC was performed without cathartic bowel preparation. It is unclear if uptake would be higher if individuals had cathartic bowel preparation (as modeled in our analysis). Our estimates of adherence with FOBT were based on data from a Veteran population over a five-year period; adherence among the general screening population (and over longer periods of time) may differ. Furthermore, adherence with FOBT may differ among those who already opted for colonoscopy.
In conclusion, compared with the currently-recommended strategy of continuing colorectal cancer screening with ten-yearly colonoscopy following an initial negative exam, rescreening at age 60 with yearly HSFOBT, yearly FIT, or five-yearly CTC yield comparable life-years with fewer complications and at a lower cost. Therefore it is reasonable to rescreen individuals with a negative colonoscopy with other modalities.