Result card

  • EFF26: What is the optimal threshold value of FIT for CRC screening?

What is the optimal threshold value of FIT for CRC screening?

Authors: Jesús González-Enríquez, Francesca Gillespie, Stefania Lopatriello, Iñaki Imaz

Internal reviewers: Pseudo125 Pseudo125

Please refer to EFF 20

We found a total of 7 studies relative to cut-off values for the amount of fecal blood that have attempted to define an optimal cut off value or have adopted producers indications and are here below described.

It is know that the positivity rate, specificity and the detection rate of advanced neoplasia varied with the cut-off level. A high-level quality review performed the analysis using different cut-off values in the meta analysis, and the superiority of FIT in the detection of advanced neoplasm was not significantly influenced. Ultimately, data extracted at a cut-off value of 75 ng/mL were considered as an acceptable trade-off between the detection rate and the number needed to scope {10}. Another review reported on 4 studies assessing FITs performances at multiple haemoglobin concentrations cut-off levels that differ from manufacture’s recommendations: in general, increasing the cut-off level of haemoglobin concentration the positivity rate decreased and the specificity and PPV increased {15}.


The faecal haemoglobin concentration at first screening predicts subsequent risk of incident colorectal neoplasia: the adjusted hazard ratios increased from 1.43 (95% CI 1.08–1.88) for baseline faecal haemoglobin concentration of 20–39 ng/mL, to 3.41 (2.02–5.75) for a baseline concentration of 80–99 ng/mL (trend test p<0·0001), relative to 1–19 ng/mL {23}. Nevertheless, findings needs to be validated for each kit separately, with a longer term follow-up, since colorectal neoplasia typically takes 10 years to develop, and using a large, population-based longitudinal follow-up study {23}.


Furthermore, f-Hb is related to severity of colorectal neoplastic disease: median f-Hb concentration was higher in those with cancer than those with no (p<0.002) or non-neoplastic (p<0.002) pathology, and those with LRA (p=0.0001); polyp cancers had lower concentrations than more advanced stage cancers (p<0.04). Higher f-Hb was also found in those with HRA than with LRA (p<0.006), large (>10 mm) compared with small adenoma (p<0.0001), and also an adenoma displaying high-grade dysplasia compared with low-grade dysplasia (p<0.009); f-Hb was significantly higher in those with a large compared with a small adenoma (p<0.0001){24}. Nevertheless, these results could be limited by the fact that false negative f-Hb were not taken into account and only participants with a positive result were referred for colonoscopy.


The cut-off level increases detection both for haemoglobin and haemoglobin-haptoglobin: when varying the cut-off level from 2 mcg/ g of stool (recommended by the manufacturer) to 14 mcg/g of stool, sensitivities for advanced adenomas and large adenomas ( ≥ 1 cm in diameter) ranged 40-24 % and 50-30 % for haemoglobin, and 33-12 % and 41-13 % for haemoglobin-haptoglobin, respectively, whereas specificities ranged 90–97 % for hemoglobin and 91–99 % for haemoglobin-haptoglobin; at cutoff values of 6 mcg/g of stool for hemoglobin and 4 mcg/g of stool for haemoglobin-haptoglobin, the specificity was ~ 95 % for both tests {25}.


A major advantage of FIT is recognized to be the automated and easier to interpret and furthermore, it measures the concentration of haemoglobin in the buffer, thus making it possible to choose the cut-off value. Nevertheless, the effect of different cut-off level in different FIT kit cannot be detected because manufacturers quote the concentration of haemoglobin not in the faeces, but in the buffer solution and this varies between different devices. Therefore, simple comparisons of cut-offs were not possible {19}.


Cut-off level detection is also linked to the colonoscopy capability: when colonoscopy capacity was unlimited, the optimal screening strategy was to administer an annual FIT with  a 50 ng/mL haemoglobin cut off level in individuals aged 45–80 years and to offer colonoscopy surveillance to all  individuals with adenomas. When colonoscopy capacity was decreasing, the optimal screening adaptation was to first increase the FIT haemoglobin cut-off value to 200 ng haemoglobin per mL and narrow the age range to 50–75 years, to restrict colonoscopy surveillance, and finally to further decrease the number of screening rounds {26}.

González-Enríquez J et al. Result Card EFF26 In: González-Enríquez J et al. Clinical Effectiveness In: Jefferson T, Cerbo M, Vicari N [eds.]. Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali; 2014. [cited 16 June 2021]. Available from: