The optimal colonoscopy screening strategy for individuals with a CRC family history had a screening interval of 3 to 5 years, depending on the number of affected relatives and their age at diagnosis. The age ranges of the optimal strategies varied from 50–75 to 42–84.
Sometimes higher thresholds than $50.000 per life-year gained are considered acceptable 44
, allowing more frequent colonoscopy screening. Increasing the threshold up to $75,000 resulted in screening intervals of 2 to 4 years and age ranges that varied from 46–78 to 43–89 (results not shown). Further increasing the threshold to $100,000 did not shorten the intervals further, but only resulted in 1 or 2 additional colonoscopies in the highest 2 risk groups.
Screening becomes somewhat less cost-effective in individuals without affected relatives since they have a lower risk than the total population (RR 0.9),. To adjust to the used threshold ICER, theoretically screening intensity needs to be decreased slightly.
There are several US guidelines for CRC screening in individuals with a family history 11, 12, 14
. In some guidelines screening starts at age 40 if someone has at least one affected FDR. In case of one FDR diagnosed after age 60, the recommended screening interval is 10 years, as in the general population. For individuals with one FDR diagnosed before age 60 and for individuals with two or more FDRs, 5-yearly colonoscopy is recommended. Others suggested, based on prospective observational studies, that screening should start at age 45–50, and that colonoscopy every 5 years would be sufficient 48, 49
. Controlled studies to analyze the effect of these strategies on incidence or mortality are not available. Our results are in line with a recommended starting age of 45, but with shorter intervals. However, note that the shorter intervals for individuals with 1FDR ≤ 50 or 2+ FDRs were approximately halve the interval for the average risk population (3–4 versus 7 years according to our results), which corresponds nicely with the 50% difference in interval as recommended in the guidelines (5 versus 10 years). The 10-yearly recommendation for the average risk population was based on expert opinion, and chosen for simplicity. This strategy was suboptimal in our analysis, because it was as effective as 3 colonoscopies every 7 years starting at age 54 but more expensive ($0.50 instead of $0.45 million). This strategy with a 7-yearly interval had an ICER of $43.000 per life-year gained, which is close to the threshold of $50.000 per life-year gained.
Lengthening the model assumption of the average dwell time for an adenoma to become cancer from 20 to 30 years did not lengthen our optimal screening interval for the average risk population. However, as expected, the incremental cost-effectiveness of 4 colonoscopies relative to 3 colonoscopies became worse due to the lower incremental effectiveness of the last colonoscopy. By lengthening the dwell time even further, the ICER of 3 colonoscopies every 7 years would eventually increase to over $50,000 per life-year gained as well and longer intervals would become optimal in combination with fewer screening rounds. Besides a longer adenoma dwell time, higher colonoscopy costs relative to the treatment costs would also challenge our conclusion that shorter screening intervals may be appropriate than currently recommended. However, this is unlikely in view of the increasing costs of chemotherapy drugs involved in CRC treatment. We looked at the influence of trends in survival and treatment costs in an earlier analysis, where more recent survival data, taking the effects of greater use of adjuvant treatment into account, had a minimal effect on the number of life-years gained 50
. This will therefore have a small impact on our results. Another important assumption is that increased cancer risk is due to an equally increased adenoma incidence across all ages. We assessed this assumption in an earlier analysis based on several colonoscopy studies 51
. Alternatively, a faster progressive development of adenomas could cause higher risk in these individuals. We found a shorter interval of 2 instead of 3 years for the highest risk group when we assumed the increased risk to be caused by a combination of a higher adenoma incidence and faster progression of the adenomas. So this would imply even more diversification in screening intensity between risk groups.
A limitation of this study is that we did not account for the number of FDRs an individual has, which affects the risk for CRC. For example, an individual with two FDRs both diagnosed with CRC is at higher risk than someone with ten FDRs, two of whom are diagnosed with CRC. Also family history, and thus the estimated risk of an individual changes over time, because relatives are being diagnosed or not with CRC. Ideally, the screening strategy is adjusted accordingly.
Our results show that individualizing screening guidelines based on family history could improve the effectiveness substantially. Individualized guidelines are more complex than the current guidelines and could confuse both physicians and screenees, resulting in lower adherence rates. Individuals could also hesitate to adhere to more frequent invasive colonoscopies, especially if their insurance company does not cover earlier or more frequent colonoscopies. Adherence generally does not influence the cost-effectiveness of screening since in influences both costs and effects, and was therefore assumed 100% in our analysis. However, lower adherence rates would obviously decrease the effectiveness of screening. On the other hand, individualized guidelines could also increase the adherence because of a better awareness of the individuals risk for CRC. Besides, it fits in the trend towards more personalized medical care, and individuals might appreciate the fact that the recommendation is based on their personal risk profile. Implementation studies should look into these issues.
Risk for CRC also depends on lifestyle. Recently, a risk prediction tool has become available that estimates an individual’s CRC risk based on a self-administered questionnaire 52, 53
. Both family history and lifestyle factors are included. Results of cost-effectiveness analyses, as those presented in this paper can be used to translate the risk estimates resulting from this prediction model to screening recommendations.
In conclusion, the optimal colonoscopy screening strategy varies considerably with the number of affected relatives and their age of diagnosis. For the high risk individuals, shorter intervals than the currently recommended 5 years may be appropriate.