Faecal haemoglobin concentration among subjects with negative FIT results is associated with the detection rate of neoplasia at subsequent rounds: a prospective study in the context of population based screening programmes in Italy

Abstract

ObjectiveTo estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer—CRC—or advanced adenoma).DesignProspective cohort of subjects aged 50–69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy.MethodsAll programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces). We assessed the AN risk at subsequent exams, the cumulative AN detection rate (DR) over the 4-year period following the second FIT and the interval CRC (IC) risk following two negative FITs by cumulative amount of f-Hb concentration over two consecutive negative FITs, using multivariable logistic regression models and the Kaplan-Meier method.ResultsThe cumulative probability of a positive FIT result over the subsequent two rounds ranged between 7.8% (95% CI 7.5 to 8.2) for subjects with undetectable f-Hb at the initial two tests (50% of the screenees) and 48.4% (95% CI 44.0 to 53.0) among those (0.7% of the screenees) with a cumulative f-Hb concentration ≥20 µg/g faeces. The corresponding figures for cumulative DR were: 1.4% (95% CI 1.3 to 1.6) and 25.5% (95% CI 21.4 to 30.2) for AN; 0.17% (95% CI 0.12 to 0.23) and 4.5% (95% CI 2.8 to 7.1) for CRC. IC risk was also associated with cumulative f-Hb levels.ConclusionThe association of cumulative f-Hb concentration with subsequent AN and IC risk may allow to design tailored strategies to optimise the utilisation of endoscopy resources: subjects with cumulative f-Hb concentration ≥20 µg/g faeces over two negative tests could be referred immediately for total colonoscopy (TC), while screening interval might be extended for those with undetectable f-Hb.

Personalised screening for colorectal cancer, ready for take-off

“…In line with these results, a recent Spanish study reported an OR for advanced neoplasia of nearly 22 for those with high faecal Hb concentrations (between 10 and 19.9 µg/g faeces) compared with those with low Hb concentrations (between 0 and 3.8 µg/g faeces) 7. Both studies reported risks that were lower than those reported by Senore et al5 This could be explained by the fact that the Italian findings were set against screenees with undetectable faecal Hb concentrations whereas the other studies compared their findings to those with low, yet not undetectable concentrations. The results of this Italian study are also in line with the results from a Dutch CRC screening cohort 8.…”

“…The Italian data published in Gut combined with the two previous similar studies from Spain and the Netherlands now firmly establish ground for development of personalised FIT screening strategies using individual actual faecal Hb data 5 7 8. These findings have the potential to help move risk stratification along and to aid public health decision makers in choosing the optimal screening strategy in FIT-based CRC screening.…”

“…The beautiful paper by Senore and colleagues in Gut provides additional support for this concept in exploring the predictive value of faecal Hb concentrations over multiple rounds of CRC screening 5. Their study used data from four Italian CRC screening programme over multiple rounds including almost 300 000 screenees.…”

The impact of hypothetical PErsonalised Risk Information on informed choice and intention to undergo Colorectal Cancer screening colonoscopy in Scotland (PERICCS)—a randomised controlled trial

“…Alternative approaches to improve transparency of information offered to screening participants could also be explored, such as providing those with a negative result with their numerical f-Hb, so that they themselves are aware of the proximity of their screening result to the threshold. This idea is supported by the findings of a recent study from Italy demonstrating that those with two consecutive negative screening test results, but a cumulative f-Hb above the cut-off for positivity had a significantly increased risk of a future diagnosis of advanced neoplasia [29]. An indication of the individual's proximity to the positivity threshold could be provided alongside strategies applying more intelligent use of FIT, such as varying the length of the screening interval according to f-Hb, with those closest to the threshold offered the opportunity to be screened more regularly than those with very low or undetectable f-Hb.…”

Optimal diagnostic accuracy of quantitative faecal immunochemical test positivity thresholds for colorectal cancer detection in primary health care: A community‐based cohort study

“…Another recent proposal is to refer for colonoscopy those patients with cumulative f-Hb concentration ≥20 μg Hb/g faeces over two 'negative' tests. 31 We believe that these data provide the basis to justify a clinical trial in which the risks and benefits of both thresholds could be prospectively compared.…”