• colorectal cancer
• faecal haemoglobin
• faecal immunochemical test
• faecal occult blood test
• screening

We read with interest the work by Haug et al published in Gut.1 Longitudinal data from 4523 participants in the first round of a faecal immunochemical test for haemoglobin (FIT)-based screening programme, of whom 3427 also participated in the second round, were studied. In both first and second rounds, a threshold of 10 µg Hb/g faeces was used. The cohort was followed up for 2 years. The cumulative positivity and the number of participants diagnosed with neoplasia over the two rounds of screening were determined and compared with a hypothetical strategy involving single round screening with use of lower faecal haemoglobin concentration (f-Hb) thresholds and omission of the second round. It was suggested that lowering the f-Hb threshold and extending the screening interval could possibly enhance population-based screening programmes.

In our pilot evaluation of FIT-based screening in Scotland, a much higher f-Hb threshold (≥80 µg Hb/g faeces) was employed.2 Moreover, a much larger cohort of screened individuals (30 893) was available for study. Seven hundred and fifty-three participants with f-Hb ≥80 µg Hb/g were referred for colonoscopy. Of 30 140 with a negative screening test result, 27 890 that had participated were eligible to be invited for the next screening round (January 2011 to January 2013). Of 24 669 responders, 450 had a positive screening test result and were referred for colonoscopy. In the two rounds of screening studied, the first with quantitative FIT using a threshold of ≥80 µg Hb/g faeces and the second using the standard guaiac faecal occult blood test/FIT two-tier reflex algorithm used in Scotland,3 the positivity in the first round was 2.5%: there were 30 screen-detected cancers (SDCs) and 31 interval cancers (ICs).4 In the first round, 753 colonoscopies were performed. At the second round, there were 25 SDC, making a total of 55 SDC over two rounds.

Assuming that IC and colorectal cancer (CRC) detected at the subsequent screening round would have been present in some form during the initial screening round, the scenarios that would have eventuated by omitting the second screening round and using lower f-Hb thresholds are listed in table 1. The f-Hb threshold that would have given double the positivity rate of that found using ≥80 µg Hb/g faeces was identified as ≥28 µg Hb/g faeces.

This f-Hb threshold would have generated the same number of colonoscopies in a single 4-year screening round as a threshold of ≥80 µg Hb/g faeces would have in two rounds of biennial screening. In this situation, which is colonoscopy resource neutral, three ICs and nine second round CRCs would have been detected during the first round of screening. It follows that the remaining 16 SDCs found in the second round would have become IC, or at least have been more advanced when detected at the next screening episode. This would have resulted in 42 SDCs diagnosed in a 4-year screening round, considerably fewer than the total of 55 SDCs with biennial screening, and the number of IC could have potentially increased from 31 to 44.

Therefore, the concept of lowering f-Hb cut-off and lengthening screening interval to improve test sensitivity without an increase in colonoscopy requirement is not supported by our data since a modest decrease in IC would be offset by the majority of second round SDC being missed. Other strategies such as the use of f-Hb concentration to determine the length of the subsequent screening interval for individual participants may be a better option when evolving to more intelligent use of FIT.