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.

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.

Introduction

After pilot studies, New Zealand implemented a national colorectal cancer (CRC) screening program in 2017 with a graduate roll out by district health board. The program invites individuals aged 60 to 74 years to perform a fecal immunochemical test (FIT), using a positivity cut-off of 40 microgram Hemoglobin per gram feces. While health disparities exist between Māori and non-Māori populations across various health domains, there has been no systematic assessment of these inequities in the context of CRC screening.

Aims & Methods

This study aimed to assess the differences on key performance indicators of the National Bowel Screening Program between Māori and non-Māori populations in New Zealand and inform policy to improve equity. In this population-based study, we used data from the national population register of invitees for CRC screening between 2017 and 2023, which contained outcomes of up to four screening rounds of the National Bowel Cancer Screening Program in New Zealand. Key performance indicators were the FIT and follow-up colonoscopy participation rate, FIT positivity rate, positive predictive value (PPV) and detection rate of advanced neoplasia (AN; CRC and advanced adenomas). Multivariate logistic regression analyses were used to assess the association between ethnicity and key performance indicators, adjusted for confounding factors such as age, sex and invitation round.

Results

A total of 1,171,205 individuals were invited for CRC screening between 2017 and 2023 for up to four screening rounds. Of these, 675,274 (57.7%) individuals participated (Table 1). Compared to European descent, the Māori, Pacific and Asian populations were less likely to participate in FIT screening, with odds ratios (OR) of 0.60, 0.37 and 0.51 respectively, while the Māori ((OR: 1.52) and Pacific (OR: 1.27) were more likely to have a positive FIT result compared to the European descent population. Participation to follow-up colonoscopy was not significantly different by ethnicity. Asian, Māori and Pacific people had a significantly lower PPV for AN compared to European descent (OR 0.67, 0.67, 0.54 respectively). The detection rate for AN was significantly higher for Māori individuals compared to the European descent population (OR 1.13), while being significantly lower for Pacific and Asian (0.78 and 0.73, respectively).

Conclusion

CRC screening outcomes in New Zealand differ significantly by ethnicity, in particular for the Māori and Pacific people, with Māori exhibiting the highest yield of CRC screening. These findings highlight the importance of increasing participation in this population subgroup. Given the disparities in screening yield, risk-based screening strategies tailored to ethnicity could also be considered.

References

1. Hill S, Sarfati D, Blakely T, Robson B, Purdie G, Chen J, et al. Survival disparities in Indigenous and non-Indigenous New Zealanders with colon cancer: the role of patient comorbidity, treatment and health service factors. Journal of Epidemiology & Community Health. 2010;64(2):117-23.

Introduction

The fecal immunochemical test (FIT), utilized for fecal hemoglobin (f-HB) detection in stool, stands as a recommended screening approach for colorectal cancer (CRC) (1). Prior research has shown the predictive ability of f-HB concentration over two previous screening rounds in predicting future risk of CRC (2). However, there remains a gap in literature on the additional benefit of incorporating more than two f-HB concentrations.

Aims & Methods

In this study, we aim to assess the added prognostic value of using three preceding rounds of f-HB concentrations compared to using two rounds in risk prediction of Advanced Neoplasia (AN) and CRC.

In our analysis, we utilize data from the fourth round of the Dutch CRC screening program. We first develop a prognostic model for detecting AN and CRC, incorporating participants age, sex, and f-HB concentrations from rounds 1, 2, and 3 as predictor variables. Similarly, we develop a separate model using only f-HB concentrations from rounds 2 and 3, along with sex and age as predictors. Model performance is assessed using receiver operating curve (AUC) and visual calibration inspection. We further report on the net classification improvement (NRI) and integrated discrimination improvement (IDI) to quantify how the models with 3 rounds of F-HB levels enhance the reclassification of participants with and without AN or CRC. Positive values of both NRI and IDI with a p-value of <0.005 indicate a significant improvement in classification of participants.

Results

Among study participants, 56959 (4.7%) had a positive FIT result, 15170 (1.2%) had AN detected and 2465 (0.2%) had CRC. The model with three rounds of f-HB levels outperformed the model with two rounds in discriminating patients with AN and CRC. Specifically, AUCs for AN and CRC were 0.76 (95% CI, 0.75-0.77) and 0.73 (95% CI, 0.66-0.74) respectively for model with three rounds of f-HB levels. Both NRI and IDI were positive with p values of <0.005 indicating an improvement in classification of participants with and without AN and CRC when using three rounds of f-HB concentrations compared to using two rounds.

Table 1: Values for AUC for models with three and two rounds of f-HB levels with age and sex as predictor variables for risk of AN and CRC

Conclusion

Our findings suggest that the model integrating three f-HB levels surpasses the two-level model in discrimination and reclassification. Therefore, using more preceding rounds of f-HB concentrations could potentially enhance personalized screening of CRC within the Dutch screening program.

References

1. Rex DK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbach T, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017;112(7):1016-30.
2. Meester RGS, van de Schootbrugge-Vandermeer HJ, Breekveldt ECH, de Jonge L, Toes-Zoutendijk E, Kooyker A, et al. Faecal occult blood loss accurately predicts future detection of colorectal cancer. A prognostic model. Gut. 2023;72(1):101-8.

Disclosure

All authors declare that they have no competing interests.