Editorial: Single colonoscopy-based colorectal cancer screening as a real-world cost-effective option

Globally, colorectal cancer (CRC) ranks third in terms of incidence but second in terms of mortality.¹ CRC screening is recommended by guidelines as it has been shown to reduce CRC incidence² and CRC-related mortality.^{2, 3} The fecal immunochemical test (FIT) and colonoscopy are both widely used for CRC screening. A systematic review and meta-analysis of six randomized controlled trials and 17 cost-effectiveness studies reported that although FIT had a detection rate of CRC comparable with colonoscopy, it had lower detection rates of any adenoma and advanced adenoma. Nonetheless, annual or biennial FIT appeared to be very cost-effective compared with colonoscopy every 10 years.⁴ However, in the real-world setting, the uptake of serial CRC screening tests remains low. A single time point screening test, although less ideal, may be more realistic. Hence, to clarify whether a single colonoscopy-based screening or a single FIT-based screening is superior is of practical relevance in the real-world setting. Currently, there is a paucity of such cost-effectiveness data.

In this issue of Journal of Gastroenterology and Hepatology, Ishibashi et al. conducted a cost-effectiveness analysis of single colonoscopy versus single FIT for CRC diagnosis and treatment.⁵ A microsimulation model was constructed based on real-world observational data that compared single colonoscopy-based screening with single FIT-based screening. The total costs of diagnosis and treatment of the detected lesions using the two strategies were calculated and the incremental cost-effectiveness ratio per life year gained assessed. It was concluded that the single colonoscopy-based strategy was more cost-effective than FIT, especially for patients aged 60–69 years, and when the adenoma detection rate (ADR) during colonoscopy exceeded 30% or the positive FIT rate was lower than 8.6% in the FIT-based strategy. This study is important and of practical relevance as it provides data demonstrating that in the context of performing only a one-time screening test, in the relevant context, a single colonoscopy may be more cost-effective than FIT-based test. A detailed costing information for both diagnosis and treatment was provided. Although the FIT test itself is cheaper, when consideration of the earlier disease states of detected colonic neoplasia and differences in treatment costs are taken into account, a single colonoscopy-based strategy could actually be more cost-effective. Another strength of the study is that it established a threshold of parameters for the colonoscopy to be effective. The main limitation to this study would be its generalizability. Costs of tests and treatment do differ between countries, and likewise, there may be differences in ADR and FIT-positive rates between different patient populations.

Cost-effectiveness analyses using validated microsimulation models are important for guiding policy decisions on CRC screening. Such analyses are not static and require updating when the parameters on which the microsimulation is based on, such as disease incidence, diagnostic performance of preexisting or emerging tests, and costs of the tests and treatment, change over the course of time. An example is the observation of increased incidence of early onset CRC and subsequent changes made to national guidelines for CRC screening age to be lowered to 45 years when it was considered cost-effective.^{6, 7} Both FIT and colonoscopy are regarded as cost-effective screening tests.⁴ However, the real-world clinical impact is limited by variable rates of uptake of such screening tests. There is interest in the use of blood-based CRC screening tests to increase screening participation. A recent health economic modeling study explored the cost-effectiveness of next-generation sequencing liquid biopsies (NGS-LB) for CRC screening in Spain, France, and Germany. The conclusion was that NGS-LB could potentially be cost-effective. Confirmation through actual clinical trials is needed.⁸ On the other hand, another modeling study from the United States concluded that triennial blood-based screening, with minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for CRC screening.⁹

The current recommended options for screening are colonoscopy, stool-based tests such as FIT and FIT-DNA, as well as imaging-based options like CT colonography and colon capsule.¹⁰ This study suggests that a single colonoscopy-based screening may be cost-effective compared to FIT, and this is of relevance to those who only want to undergo a single screening procedure in their lifetime. To quote Johann Wolfgang von Goethe, “Knowing is not enough; we must apply. Willing is not enough; we must do.” The key to successful CRC screening is acceptance and actual uptake of the screening test. Even if there is a reluctance to undergo serial tests over time, a one-time screening test is still of benefit.