Making colorectal cancer screening FITTER for purpose with quantitative faecal immunochemical tests for haemoglobin (FIT).

Colorectal cancer (CRC) is a major cause of disease worldwide and a leading cause of mortality. Fortunately, CRC is a disease that meets the criteria for successful early detection and treatment through population screening. Moreover, CRC incidence is decreasing in some countries which, at least in part, may be due to the establishment and expansion of screening programmes. Screening tests can be applied either in one-step screening using colonoscopy or flexible sigmoidoscopy, or in two-step screening using simpler non-invasive tests such as faecal tests for occult blood. Tests for the assessment of blood in faeces are widely considered to be the best currently available for two-step screening and are very suited to large scale population-based screening programmes [1]. Traditionally, guaiac-based faecal occult blood tests (gFOBT) have been used and four randomised controlled trials, in the setting of population-based programmes, showed a modest intention-to-treat decrease in mortality [2] that has been demonstrated to occur also in practice [3, 4]. However, gFOBT have many well-known limitations [5] that do not apply to the newer faecal immunochemical tests (FIT) for haemoglobin (Hb) [6]. FIT are now being widely adopted in new screening programmes and existing programmes using gFOBT are moving to FIT. The merits of FIT over gFOBT are summarised in this issue of the journal by Huang and colleagues [7], who collected faeces in a single specimen collection device from a representative random population in China. The specimens were then analysed using one quantitative and two qualitative FIT. The authors documented the cut-off haemoglobin concentration which they used for referral of the participants for colonoscopy as 20 μg Hb/g faeces for the quantitative FIT and 20 μg Hb/g faeces and 40 μg Hb/g faeces for the two qualitative FIT. The appropriate use by the authors of μg Hb/g faeces for reporting FIT concentrations is consistent with good practice, and our recent recommendations [8], since these units facilitate more objective comparison of data across different FIT, a process impeded by the current wide use of proprietary ng Hb/mL buffer units. The study demonstrated different positivity rates for the two qualitative FIT, evidence of the different faecal Hb cut-off concentration needed for a colour change on the immunochromatographic test strips. This is an important finding which confirms previous evidence that available qualitative FIT are not all the same [9]. The cut-off faecal Hb for qualitative FIT are set by the manufacturers and, as a consequence, it is the manufacturers that determine the important clinical outcomes. As the cut-off faecal Hb concentration is decreased, the positivity rate and colonoscopy demand increase, the clinical sensitivity increases, specificity decreases, positive-predictive value decreases and number needed to scope increases. Surely this critical clinical variable, the cut-off faecal Hb concentration, should be set by screening programme organisers so that effective use of the endoscopic resources is enabled and clinical expectations met. Huang et al. provide a novel solution to the setting of the cut-off faecal Hb concentration for qualitative FIT [7]. The criteria for a positive result for the qualitative FIT were set according to the density of the colour appearing in the test strip. The authors created 10 positive criteria for the qualitative FIT by measuring the density of the colour in the strips of the qualitative FIT, producing a colour ladder from faint pink to dark red with the different grades corresponding to increasing faecal Hb concentrations. Faecal specimens with a test strip colour darker than the designated cut-off colour grade were regarded as positive. Setting the cut-off subjectively at a specific colour rather than the simple presence or absence of colour for one of the qualitative FIT did improve the comparability of results across the quantitative and both qualitative FIT. However, we are not convinced that this approach could be successfully adopted for large-scale population screening programmes. Indeed, the authors state that it would be necessary to intensify quality control and refine positive criteria for qualitative FIT to be used for CRC screening and suggest that, otherwise, quantitative FIT might be a better choice [7]. We agree and have recently documented