Introduction
Previous studies of fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening programs have demonstrated that fecal hemoglobin (f-Hb) concentrations below the FIT positivity threshold, are associated with a higher risk of advanced neoplasia (AN) in subsequent screening rounds. These findings highlight the potential of risk-stratified CRC screening based on prior f-Hb concentrations. However, prospective evidence of this approach is lacking.
Aims & Methods
The aim of this randomized controlled trial (RCT) was to evaluate the of yield risk-tailored screening intervals based on prior f-Hb concentrations in a FIT-based CRC screening. The PERFECT‑FIT study (NCT05423886) recruited individuals aged 57 to 72 in 2022 and 2023 in the Netherlands. They were randomly assigned to either tailored screening intervals based on f-Hb concentrations measured in their prior negative FIT (1 year for >15 to <47 µg Hb/g feces, 2 years for >0 to ≤15 µg Hb/g feces, and 3 years for 0 µg Hb/g feces; intervention group) or the standard 2-year screening interval (control group). The primary outcome was the detection of AN (CRC and advanced adenomas) over one screening round.
Results
In total, 20,088 participants provided informed consent and were randomly assigned to either the control group (n = 10,211) or the intervention group (n=9,877). In the intervention group, 352 (3.6%) participants were assigned to a 1-year screening interval, 350 (3.5%) to a 2-year interval and 9,175 (92.9%) to a 3-year interval. 19,547 study participants returned their FIT (97.3%). The positivity rate of FIT was significantly higher in the intervention group (4.4%) than in the control group (3.7%; p=0.03). The detection rate of AN showed no significant difference between the intervention group (1.0%) and the control group (0.8%; p=0.21, Table 1). Within the intervention group, detection rate of AN for the extended 3-year interval (0.7%) was substantially lower than that of the 1-year (3.5%) and 2-year interval (5.0%). It was similar to that of the total control group, in which all individuals had received an uniform 2-year screening interval (Table 1).
Conclusion
In this nationwide RCT on risk-stratified CRC screening, the majority of individuals were classified as low risk based on undetectable f-Hb concentrations and were offered an extended screening interval. Risk-tailored screening intervals did not result in a higher detection rate of AN after one screening round for the total intervention group compared with the control arm. However, the yield among those assigned to an extended screening interval was comparable to that of the control group. These findings suggest that screening intervals can be safely extended for low-risk individuals, potentially improving screening efficiency without compromising screening yield.
Table 1: Detection rates of advanced neoplasia among participants in the control group and the intervention group in the PERFECT-FIT RCT, including the three intervention subgroups.
| Group | Total participants
| Advanced Neoplasia
| Detection rate (%, 95%CI) | p value |
| Control | 9963 | 79 | 0.8 (0.6-1.0) |
|
| Intervention | 9584 | 93 | 1.0 (0.8-1.2) | 0.21
|
1 year
| 347
| 12
| 3.5 (1.9-6.1)
|
|
2 year
| 341
| 17
| 5.0 (3.0-8.0)
|
|
3 year
| 8896
| 64
| 0.7 (0.6-0.9)
|
|
References
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3. Breekveldt ECH, Toes-Zoutendijk E, de Jonge L, Spaander MCW, Dekker E, van Kemenade FJ, van Vuuren AJ, Ramakers CRB, Nagtegaal ID, van Leerdam ME, Lansdorp-Vogelaar I. 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 Gastroenterol. 2023;23(1):45. doi: 10.1186/s12876-023-02670-1.
Disclosure
The authors have received research funding, unrelated to the present study, from Sentinel, Sysmex, Medtronic, and Norgine.