Population-based colorectal cancer screening programmes using a faecal immunochemical test: should faecal haemoglobin cut-offs differ by age and sex?

Abstract

Background: The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test (FIT). Although, colorectal cancer (CRC) screening with biannual (FIT) has shown to reduce CRC mortality, the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy, and thus, harms related to false results might not be underestimated. Current CRC screening programmes use a single faecal haemoglobin concentration (f-Hb) cut-off for colonoscopy referral for both sexes and all ages. We aimed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion.

Methods: Prospective cohort study using a single-sample faecal immunochemical test (FIT) on 444,582 invited average-risk subjects aged 50-69 years. A result was considered positive at ≥20 μg Hb/g faeces. Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs.

Results: We analysed 17,387 positive participants in the programme who underwent colonoscopy. Participation rate was 66.5%. Men had a positivity rate for f-Hb of 8.3% and women 4.8% (p < 0.0001). The detection rate for advanced neoplasia (cancer plus advanced adenoma) was 44.0‰ for men and 15.9‰ for women (p < 0.0001). The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off. However, the loss in CRC detection increased by up to 28.1% in men and 22.9% in women. CRC missed were generally at early stages (Stage I-II: from 70.2% in men to 66.3% in women).

Conclusions: This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs. We found differences in positivity rates, neoplasia detection rate, number needed to screen, and interval cancers in men and women and in younger and older groups. However, there are factors other than sex and age to consider when consideration is given to setting the f-Hb cut-off.

Keywords: Adenoma; Colorectal cancer; Faecal immunochemical test; Faecal occult blood test; Interval cancers; Screening.

Fig. 1

Study flow diagram

Fig. 2

Number Needed to Screen to detect Advanced Neoplasia (AN) (a) and the Odds Ratio for the loss in detection of AN (b) Men versus women through increasing the faecal haemoglobin cut-off. (*p < 0.001; ^† p < 0.05; ^‡no significance). (^¥Cut-off 50 μg Hb/g faeces in men = 509 [95% CI: 333–1000])

Fig. 3

Relation between saving colonoscopies (SC) and lesion loss upon increasing the faecal haemoglobin concentration cut-off by sex. Dotted lines represent lesion detection rates (for colorectal cancer (CRC) and advanced adenoma (AA)) and solid lines saved colonoscopies. The left Y axis represents lesion detection rate and the right Y axis the percentage of colonoscopies saved. Saving Colonoscopies: the percentage of colonoscopies that will not be performed in the programme by increasing the f-Hb cut-off, due to the reduction of positivity rate

Fig. 4

Relation between saving colonoscopies (SC) and lesion losses upon increasing the cut-off level of the FIT by sex and age group. Dotted lines express lesion detection rates (colorectal cancer (CRC) and advanced adenoma (AA)) and solid lines saved colonoscopies. The left Y-axis represents lesion detection rate and the right axis the percentage of colonoscopies saved. Saving Colonoscopies: the percentage of colonoscopies that will not be performed in the programme by increasing the f-Hb cut-off, due to the reduction of positive rate