Optimal cut-off value for detecting colorectal cancer with fecal immunochemical tests according to age and sex

Abstract

In the fecal immunological test, a suitable cut-off value may be selected to classify results as either positive or negative. Our aim is to estimate the optimal cut-off value for detecting colorectal cancer in different age and sex groups. This is a multicentric retrospective cohort study of participants in CRC screening programs with FIT between 2006 and 2012. A total of 545,505 participations were analyzed. Cancers diagnosed outside of the program were identified after a negative test result (IC_test) up until 2014. The Wilcoxon test was used to compare fecal hemoglobin levels. ROC curves were used to identify the optimal cut-off value for each age and sex group. Screening program results were estimated for different cut-off values. The results show that the Hb concentration was higher in colorectal cancer (average = 179.6μg/g) vs. false positives (average = 55.2μg/g), in IC_test (average = 3.1μg/g) vs. true negatives (average = 0μg/g), and in men (average = 166.2μg/g) vs. women (average = 140.2μg/g) with colorectal cancer. The optimal cut-off values for women were 18.3μg/g (50-59y) and 14.6μg/g (60-69y), and 16.8μg/g (50-59y) and 19.9μg/g (60-69y) for men. Using different cut-off values for each age and sex group lead to a decrease in the IC_test rate compared to the 20μg/g cut-off value (from 0.40‰ to 0.37‰) and an increase in the false positive rate (from 6.45% to 6.99%). Moreover, test sensitivity improved (90.7%), especially in men and women aged 50-59y (89.4%; 90%) and women aged 60-69y (90.2%). In conclusion, the optimal cut-off value varies for different sex and age groups and the use of an optimal cut-off value for each group improves sensitivity and leads to a small decrease in IC_tests, but also to a larger increase in false positives.

Optimizing the colorectal cancer screening programme using faecal immunochemical test (FIT) in Flanders, Belgium from the “interval cancer” perspective

“…Our results suggest that 15 µg Hg/g should be the lowest FIT cut-off that a CRC screening programme should aim for, regardless of the patient’s gender and age. This recommendation is supported by a recent study by Vanaclocha-Espi et al which found the optimal FIT cut-off of around 15 µg Hg/g for the subgroup of women aged 60–69, which had the lowest FIT sensitivity among the subgroups evaluated (women and men, aged 50–59 and 60–69) [ 51 ].…”

Interval Cancer in Population-Based Colorectal Screening Programmes: Incidence and Characteristics of Tumours

“…When this type of FOBT is used in screening, a cut-off point is applied to determine whether a result is positive or negative. It has also been demonstrated that the established cut-off point affects the IC rate, as can be seen in a previous study that observed how different FIT cut-off points lead to changes in the IC rate [11]. Other variables such as sex and age have been linked to the occurrence of IC, with studies showing that IC is more frequent in men and older populations [12,13].…”

“…The cut-off point for the FIT was 20 µg/g and a colonoscopy was offered as a confirmatory diagnostic test. The characteristics of these programmes and the outcomes associated with this cohort can be found in previous studies by Vanaclocha-Espí et al, 2021 and 2019 [11,17].…”

Interval post-colonoscopy colorectal cancer following a negative colonoscopy in a fecal immunochemical test-based screening program

“…Several factors should be considered, such as systematic false-positive FIT results, costs, and the capacity of FIT laboratories and colonoscopy centers. Moreover, if iPCCRC risk is to be considered in relation to FIT IC risk, the chosen FIT positivity cutoff should be taken into account, as it is a determinant of FIT IC risk 37 .…”