Introduction
There is growing evidence that the balance of harms and benefits of colorectal cancer (CRC) screening can be improved by risk stratification. One way to stratify participants is to assign a personalized invitation interval based on prior screening test results. Previous studies have shown that prior hemoglobin (Hb) concentrations determined by fecal immunochemical test (FIT), have greater predictive power for the detection of CRC in the next screening round than age and sex (1-3). Therefore, a randomized controlled trial, the PERFECT-FIT study (4), was initiated within the Dutch national CRC screening program in which participants with a prior negative FIT are invited using tailored invitation intervals (1,2 or 3 years) based on prior Hb concentrations. We aimed to investigate long-term outcomes of such personalized CRC screening based on prior Hb concentrations and to compare those to uniform CRC screening.
Aims & Methods
We simulated the Dutch national CRC screening program using a microsimulation model, MISCAN-Colon, to mimic the natural history of CRC and long-term outcomes of CRC screening interventions. We added a module to MISCAN-Colon that explicitly simulates a Hb concentration for every participant based on their age, sex, CRC state and an individual risk factor. Next, to mimic the PERFECT-FIT study, all participants with a negative FIT got assigned to either the low (0 µg Hb/g), intermediate (>0-15 µg Hb/g) or high (>15-<47 µg Hb/g) risk category. We evaluated different invitation intervals (ranging between 0.5 and 4 years) for each risk category and estimated short- and long-term effects of the different screening strategies. We compared each personalized screening strategy to uniform biennial screening. Using cost-effectiveness analysis with a willingness-to-pay threshold per QALY gained of €20,000,-, we determined optimal invitation intervals for each risk category, assuming (i) unlimited colonoscopy capacity and (ii) current colonoscopy capacity levels.
Results
Uniform biennial screening resulted in 177 QALYs gained and €101,852 saved compared to no screening per 1,000 individuals (Table 1). The PERFECT-FIT strategy resulted in 162 QALYs gained and €111,248 saved. The optimal invitation interval was 1 year for the low-risk group and 6 months for the intermediate and high-risk groups with 209 QALYs gained and €19,828 saved. With limited colonoscopy capacity, the optimal invitation interval changed to 2.5 years for the low-risk group, 1 year for the intermediate-risk group and 6 months for the high-risk group with 180 QALYs gained and €124,640 saved.
Table 1 Model outcomes per 1,000 individuals.
| Strategy* | FITs | Colonoscopies | CRC diagnoses | CRC death | Cost** | QALYs gained** | ICER |
| No screening | 0 | 0 | 86 | 38 | 0 | 0 | Dominated |
| Uniform 2 – 2 – 2 | 8,781 | 549 | 57 | 18 | -101,852 | 177 | Dominated |
| PERFECT-FIT 3 – 2 – 1 | 6,449 | 478 | 60 | 20 | -111,248 | 162 | Dominated |
| 2.5 – 1 – 0.5 | 7,896 | 547 | 57 | 18 | -124,640 | 180 | Reference |
| 2 – 0.5 – 0.5 | 9,733 | 609 | 54 | 17 | -115,337 | 192 | 752 |
| 1.5 – 0.5 – 0.5 | 12,234 | 675 | 51 | 16 | -88,729 | 201 | 2,905 |
| 1 – 0.5 – 0.5 | 16,829 | 776 | 48 | 15 | -19,828 | 209 | 8,504 |
| 0.5 – 0.5 – 0.5 | 27,830 | 974 | 44 | 14 | 180322 | 216 | 29,775 |
* The strategy name indicates the invitation interval for, respectively, the low, intermediate and high risk group. ** Compared to no screening
Conclusion
The optimal personalized CRC screening strategy is more cost-effective than uniform biennial screening, both with unrestricted and restricted colonoscopy capacity. Consequently, personalizing CRC screening invitation intervals based on prior FIT results may be an important next step to improve the balance between the harms and benefits of screening.
References
1. Grobbee EJ, Schreuders EH, Hansen BE, Bruno MJ, Lansdorp-Vogelaar I, Spaander MCW, et al. Association Between Concentrations of Hemoglobin Determined by Fecal Immunochemical Tests and Long-term Development of Advanced Colorectal Neoplasia. Gastroenterology. 2017;153(5):1251-9.e2.
2. Senore C, Zappa M, Campari C, Crotta S, Armaroli P, Arrigoni A, et al. Faecal haemoglobin concentration among subjects with negative FIT results is associated with the detection rate of neoplasia at subsequent rounds: a prospective study in the context of population based screening programmes in Italy. Gut. 2020;69(3):523-30.
3. Chen LS, Yen AMF, Chiu SYH, Liao CS, Chen HH. Baseline faecal occult blood concentration as a predictor of incident colorectal neoplasia: Longitudinal follow-up of a Taiwanese population-based colorectal cancer screening cohort. Lancet Oncol. 2011;12(6):551-8.
4. Breekveldt ECH, Toes-Zoutendijk E, de Jonge L, Spaander MCW, Dekker E, van Kemenade FJ, et al. Personalized colorectal cancer screening: study protocol of a mixed-methods study on the effectiveness of tailored intervals based on prior f-Hb concentration in a fit-based colorectal cancer screening program (PERFECT-FIT). Bmc Gastroenterology. 2023;23(1):1-10.
