Gender Differences in Fecal Immunochemical Test Performance for Early Detection of Colorectal Neoplasia.

BACKGROUND & AIMS: Fecal immunochemical tests (FITs) are used widely in colorectal cancer screening. Programs use the same fecal hemoglobin threshold for colonoscopy referral for men and women, but it is unclear whether FIT performs equally in both sexes. We therefore assessed FIT performance in men and women. METHODS: A prospective cohort study was performed, in which a total of 10,008 average-risk subjects (age, 50-74 y) were invited for first-round screening and 8316 average-risk subjects (age, 51-74 y) were invited for second-round screening with a single FIT. Subjects with a hemoglobin (Hb) level of 10 µg hemoglobin (Hb)/g (or ≥50 ng/mL) feces or higher were referred for colonoscopy. The test characteristics were assessed by sex for a range of FIT cut-off values. RESULTS: In total, 59.8% of men and 64.6% of women participated in the first round (P < .001). At a cut-off level of 10 µg Hb/g feces, the positivity rate was significantly higher among men (10.7%) compared with women (6.3%; P < .001) in the first round. The detection rate of advanced neoplasia was 4.4% for men and 2.2% for women (P < .001) in the first round. The positive predictive value for advanced neoplasia in the first round was 42% for men and 37% for women (P = .265). A significantly higher false-positive rate in men (6.3%) than in women (4.1%; P < .001) was found. Similar differences in these test characteristics were seen in the second round. CONCLUSIONS: At a cut-off level of 10 µg Hb/g feces the FIT positivity rate was higher in men, reflected by both a higher detection rate and a higher false-positive rate. The use of the same cut-off value in men and women in FIT screening is recommended based on equal test performance in terms of positive predictive value.

Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening.

OBJECTIVE: The sensitivity and specificity of a single faecal immunochemical test (FIT) are limited. The performance of FIT screening can be improved by increasing the screening frequency or by providing more than one sample in each screening round. This study aimed to evaluate if two-sample FIT screening is cost-effective compared with one-sample FIT. DESIGN: The MISCAN-colon microsimulation model was used to estimate costs and benefits of strategies with either one or two-sample FIT screening. The FIT cut-off level varied between 50 and 200 ng haemoglobin/ml, and the screening schedule was varied with respect to age range and interval. In addition, different definitions for positivity of the two-sample FIT were considered: at least one positive sample, two positive samples, or the mean of both samples being positive. RESULTS: Within an exemplary screening strategy, biennial FIT from the age of 55-75 years, one-sample FIT provided 76.0-97.0 life-years gained (LYG) per 1000 individuals, at a cost of € 259,000-264,000 (range reflects different FIT cut-off levels). Two-sample FIT screening with at least one sample being positive provided 7.3-12.4 additional LYG compared with one-sample FIT at an extra cost of € 50,000-59,000. However, when all screening intervals and age ranges were considered, intensifying screening with one-sample FIT provided equal or more LYG at lower costs compared with two-sample FIT. CONCLUSION: If attendance to screening does not differ between strategies it is recommended to increase the number of screening rounds with one-sample FIT screening, before considering increasing the number of FIT samples provided per screening round.

Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening.

OBJECTIVE: Colorectal cancer screening by means of faecal immunochemical tests (FITs) requires successive screening rounds for an optimal preventive effect. However, data on the influence of the length of the screening interval on participation and diagnostic yield are lacking. Repeated FIT screening was therefore performed in a population-based trial comparing various repeat intervals. DESIGN: 7501 Dutch individuals aged 50-74 years were randomly selected and invited for two 1-sample FIT screening rounds (haemoglobin (Hb) concentration ≥ 50 ng/ml, corresponding to 10 µg Hb/g faeces) with intervals of 1 (group I), 2 (group II) or 3 years (group III). RESULTS: In group I, participation was 64.7% in the first screening round and 63.2% in the second. The corresponding percentages for groups II and III were 61.0% vs 62.5% and 62.0% vs 64.0%. Triennial screening resulted in a higher participation rate in the second screening round compared with annual screening (p=0.04). The overall positivity rate in the second screening round was significantly lower compared with the first round (6.0% vs 8.4%; OR 0.69, 95% CI 0.58 to 0.82) and did not depend on interval length (p=0.23). Similarly, the overall detection rate of advanced neoplasia was significantly lower in the second round compared with the first screening round (1.9% vs 3.3%; OR 0.57, 95% CI 0.43 to 0.76) and also did not depend on interval length (p=0.62). The positive predictive value of the FIT did not significantly change over time (41% vs 33%; p=0.07). CONCLUSION: The total number of advanced neoplasia found at repeat FIT screening is not influenced by the interval length within a range of 1-3 years. Furthermore, there is a stable and acceptably high participation in the second screening round. This implies that screening intervals can be tailored to local resources.

Are fecal immunochemical test characteristics influenced by sample return time? A population-based colorectal cancer screening trial.

OBJECTIVES: Fecal immunochemical tests (FIT) are preferred over guaiac-based fecal occult blood testing as colorectal cancer (CRC) screening tool. However, hemoglobin (Hb) degradation over time may influence FIT outcome. We therefore evaluated the effect of sample return time on FIT performance characteristics in a population-based CRC screening trial. METHODS: A representative random sample of the Dutch population (n=17,677), aged 50-74 years, was invited for FIT screening (OC-Sensor Micro; cutoff ≥ 50 ng Hb/ml). Sample return time was defined as the interval in days between fecal sampling and FIT laboratory delivery. Moreover, a random sample of positive FITs were selected to be stored at room temperature and re-tested every 3-4 days. RESULTS: In total, 8,958 screenees fulfilled our inclusion criteria. The mean sample return time was 3 days (± 3). Overall, 792 screenees (8.8%) had a positive test. Between the sample return time groups, the positivity rate (PR) varied between 7.7 and 9.0%. No statistically significant associations were found between PR or detection rate (DR) and the different sample return time groups (P value=0.84 and 0.76, respectively). For the laboratory experiment, 71 positive FITs were stored at room temperature and re-tested with standard intervals. The mean daily fecal Hb decrease was 5.88% per day (95% confidence interval 4.78-6.96%). None of the positive FITs became negative before 10 days after fecal sampling. CONCLUSIONS: This population-based CRC screening trial demonstrates that both the PR and DR of FITs do not decrease with prolonged sample return times up to 10 days. This means that a delay in sending the FIT back to the laboratory, of up to at least 1 week, does not necessitate repeat sampling in case of a negative test result. These data support the use of FIT-based screening as a reliable tool for nationwide CRC screening programs.

Diagnostic yield improves with collection of 2 samples in fecal immunochemical test screening without affecting attendance.

BACKGROUND & AIMS: The fecal immunochemical test (FIT) is superior to the guaiac-based fecal occult blood test in detecting neoplasia. There are not much data on the optimal number of FITs to perform. We conducted a population-based trial to determine attendance and diagnostic yield of 1- and 2-sample FIT screening. METHODS: The study included 2 randomly selected groups of subjects aged 50-74 years (1-sample FIT, n=5007; 2-sample FIT, n=3197). The 2-sample group was instructed to collect fecal samples on 2 consecutive days. Subjects were referred for colonoscopy when at least 1 sample tested positive (≥50 ng hemoglobin/mL). RESULTS: Attendance was 61.5% in the 1-sample group (2979 of 4845; 95% confidence interval, 60.1%-62.9%) and 61.3% in the 2-sample group (1875 of 3061; 95% confidence interval, 59.6%-63.0%; P=.84). In the 1-sample group 8.1% tested positive, and in the 2-sample group 12.8% had at least 1 positive test outcome and 5.0% had 2 positive test outcomes (P<.05). When the mean from both test results in the 2-sample group was used, 10.1% had a positive test outcome (P<.05). The detection rates for advanced neoplasia were 3.1% in the 1-sample group, 4.1% in the 2-sample group with at least 1 positive test outcome, 2.5% when both test results were positive, and 3.7% among subjects with the mean from both test results being positive. CONCLUSIONS: There is no difference in attendance for subjects offered 1- or 2-sample FIT screening. The results allow for the development of efficient FIT screening strategies that can be adapted for local colonoscopy capacities, rather than varying the cut-off value in a 1-sample strategy.