Comparison and commutability study among four faecal immunochemical tests (FIT) systems.

OBJECTIVES: Faecal immunochemical tests for haemoglobin (FIT) are used in colorectal cancer screening programs around the world and increasingly for triage of symptomatic patients. FIT results are currently not traceable to a common reference standard and results obtained on various FIT systems may not be equivalent. The size of the bias between the systems is difficult to quantify due to the complex pre-analytical aspects of FIT. METHODS: This study aimed to quantify the bias and the correlation between four FIT systems by measuring a panel of 38 faecal samples while limiting the effect of the pre-analytical aspects. In addition, the commutability of seven candidate reference materials (RM) was assessed. RESULTS: Pairwise method comparisons based on faecal samples demonstrated Pearson correlation coefficients ranging between 0.944 and 0.970 and an average proportional bias of -30 to -35 % for one FIT system compared to the other three. The relative standard deviation among biases of the individual samples was around 20 %. Due to these sample specific differences, no decisive conclusions could be drawn in the commutability study. However, two candidate RMs, prepared in the FIT system-specific storage/extraction buffers, had a better commutable profile than the other five. CONCLUSIONS: The use of a common threshold for all FIT systems is currently not possible due to the presence of a proportional bias. We have identified potential commutable RMs to take to further studies on the production of a common calibrator, with the aim being to reduce the analytical bias observed on different FIT systems.

[Évaluation de la gravité du cancer colorectal dépisté dans le contexte de la crise sanitaire liée au COVID19 en région Ile-de-France]. / Evaluation of the severity of screened colorectal cancer in the context of the health crisis linked to COVID19 in Ile-de-France region.

BACKGROUND: After the announcement in March 2020 of the COVID-19 pandemic, colorectal cancer (CRC) screening programs were suspended in several countries. Compared to the lesions detected during previous campaigns, this study aims to assess the severity of CRC detected during the 2020 screening campaign in Île-de-France, the French region most affected by the 1st wave of the pandemic. METHODS: The descriptive and etiological study included all faecal immunochemical test (FIT) results carried out between January 2017 and December 2020 on people aged 50-74, living in Île-de-France. First, the proportion of colonoscopies performed within one month (One-month-colo) following FIT; the yield of colonoscopy (proportion of colonoscopies with a neoplasm lesion among those performed) and CRC severity (TNM Classification, Level-0: T0/N0/M0, Level-1: T1/T2/N0/M0, Level-2: T3/T4/N0/M0; Level-3: T3/T4/N1/M0; Level-4: M1) were described in 2020 compared to previous campaigns (2017, 2018, and 2019). Subsequently, the link between the level of CRC severity and the predictive factors, including campaign year and time to colonoscopy, was analysed using polytomous multivariate regression. RESULTS: The one-month-colo (2017: 9.1% of 11,529 colonoscopies; 2018: 8.5% of 13,346; 2019: 5.7% of 7,881; 2020: 6.7% of 11,040; p < 0.001), the yield (65.2%, 64.1%, 62.4%, 60.8% respectively, p < 0.001) were significantly different between campaigns. The proportion of CRC level-4 (4.8% in 2017 (653 CRC); 7.6% in 2018 (674 CRC); 4.6% in 2019 (330 CRC) and 4.7% in 2020 (404 CRC); p < 0.29) was not significantly different between campaigns. The probability of having CRC with a high severity level was inversely related to the time to colonoscopy but not to the campaign year. Compared to patients having undergone colonoscopy within 30 days, the odds were significantly reduced by 60% in patients having undergone colonoscopy after 7 months (adjusted Odds-Ratio: 0.4 [0.3; 0.6]; p < 0.0001). CONCLUSIONS: The French indicators were certainly degraded before the first wave of the COVID-19. The delay in access to colonoscopy as well as its extension induced by the COVID-19 crisis had no impact in terms of cancer severity, due to a discriminatory approach prioritizing patients with evident symptoms.

Understanding colorectal cancer risk for symptomatic patients in primary care: A cohort study utilising faecal immunochemical tests and blood results in England.

BACKGROUND: A faecal immunochemical tests (FIT) cut-off of ≥10 µg Hb/g faeces is now recommended in the UK as a gateway to urgent (suspected cancer) investigation for colorectal cancer (CRC), based on an expected CRC risk threshold of 3%. AIMS: To quantify the risk of CRC at FIT cut-offs by age, haemoglobin and platelet strata. METHODS: A cohort study of a symptomatic CRC pathway based on primary care FIT tests in Nottingham, UK (November 2017-2021) with 1-year follow-up. Heat maps showed the cumulative 1-year CRC risk using Kaplan-Meier estimates. RESULTS: In total, 514 (1.5%) CRCs were diagnosed following 33,694 index FIT requests. Individuals with a FIT ≥ 10 µg Hb/g faeces had a >3% risk of CRC, except patients under the age of 40 years (CRC risk 1.45% [95% CI: 0.03%-2.86%]). Non-anaemic patients with a FIT < 100 µg Hb/g faeces had a CRC risk of <3%, except those between the age of 70 and 85 years (5.26% 95% CI: 2.72%-7.73%). Using a ≥3% CRC threshold in patients <55 years calculated using FIT, age and anaemia might allow 160-220 colonoscopies per 10,000 FITs to be re-purposed, at a cost of missing 1-2 CRCs. CONCLUSIONS: FIT alone with a single cut-off is unlikely to be a panacea for optimising CRC diagnosis, as risk varies by FIT, age and anaemia when faecal haemoglobin levels are below 100 µg Hb/g. Tailored FIT cut-offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold.

Replicate and repeat faecal immunochemical tests in symptomatic patients: A systematic review.

BACKGROUND: Faecal Immunochemical tests (FITs) in the assessment of patients presenting with symptoms have generally used a single sample. Little evidence pertains to the use of replicate, where a number of tests are done prior to decision-making or repeat FIT, where additional FIT are performed following clinical decision-making. Overwhelmingly, research has focussed on FIT to help identify colorectal cancer (CRC). The aim of this review is to assess the available literature concerning replicate and repeat FIT in symptomatic patients to help generate consensus and guide future research. METHODS: The terms 'faecal immunochemical test' or 'FIT' were combined with 'multiple' or 'repeat'. EMBASE, Medline and PubMed database and other searches were conducted. All papers published in English were included with no exclusion date limits until November 2021. RESULTS: Of the 161 initial papers screened, seven were included for review. Qualitative and quantitative FIT outcomes were assessed in the studies. The primary aims of most related to whether replicate FIT increased diagnostic yield of CRC, with colonoscopy used as the reference standard. One publication assessed the impact of a new COVID-adapted pathway on CRC detection. No consensus on replicate FIT was apparent. Some concluded that FITs may help minimise missed CRC diagnoses: others showed no increase in diagnostic yield of CRC. CONCLUSIONS: Current evidence on replicate and repeat FIT is both minimal and conflicting. FIT is a superb clinical tool, but significant gaps surrounding application remain. Further studies relating to replicate and repeat FIT are required.

Use of faecal immunochemical tests common in patients with suspected colorectal cancer but unrelated to travel distance to secondary care: a population-based study from Swedish primary care.

BACKGROUND: Evidence is increasing for the use of faecal immunochemical tests (FITs) for occult blood as diagnostic tools when colorectal cancer can be suspected. FITs have been used for this purpose in Swedish primary care since around 2005 despite absence of supporting guidelines. To our knowledge, the extent of this use has not been studied. OBJECTIVE: To investigate the use of FITs as diagnostic tools, and if the use was related to patient age, sex and travel time from primary care to diagnostic facilities in secondary care. DESIGN: Population-based retrospective study using data from electronic health records. SETTING AND SUBJECTS: Patients ≥18 years that provided FITs in primary care in five Swedish health care regions during 2015. Driving times from their primary care centres to secondary care were calculated. MAIN OUTCOME MEASURES: The proportion of patients that provided FITs was calculated for each region, different age intervals and grouped driving times. RESULTS: 18,913 patients provided FITs. The proportion of listed patients in the five regions that provided FITs increased with age: 0.86-1.2% for ages <65 years, 3.6-4.1% for ages 65-79 years and 3.8-6.1% for ages ≥80 years. Differences between the regions were small. There was no overall correlation between the proportion of patients that provided FITs and driving time to secondary care. CONCLUSION: FITs were used extensively in Swedish primary care with a higher use in older age groups. There was no tendency towards a higher use of FITs at primary care centres with longer driving times to secondary care.Key PointsEvidence is increasing for the use of faecal immunochemical tests (FITs) as diagnostic tools when colorectal cancer can be suspected. We investigated the use of FITs in Sweden.FITs were used extensively in primary care especially in older age groups.There were small differences in the use of FITs between five studied health care regions.There was no tendency towards a higher use of FITs at primary care centres with longer driving times to diagnostic facilities in secondary care.

Combining faecal immunochemical testing with blood test results for colorectal cancer risk stratification: a consecutive cohort of 16,604 patients presenting to primary care.

BACKGROUND: Faecal immunochemical tests (FITs) are used to triage primary care patients with symptoms that could be caused by colorectal cancer for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting. METHODS: Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospitals NHS Foundation Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared. RESULTS: One hundred thirty-nine colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 µg Hb/g were 92.1 and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test results with FIT increased specificity but decreased sensitivity. Multivariable models including blood tests performed similarly to FIT alone. CONCLUSIONS: FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.

Short-term outcomes of a COVID-adapted triage pathway for colorectal cancer detection.

AIM: The dramatic curtailment of endoscopy and CT colonography capacity during the coronavirus pandemic has adversely impacted timely diagnosis of colorectal cancer (CRC). We describe a rapidly implemented COVID-adapted diagnostic pathway to mitigate risk and maximize cancer diagnosis in patients referred with symptoms of suspected CRC. METHOD: The 'COVID-adapted pathway' integrated multiple quantitative faecal immunochemical tests (qFIT) to enrich for significant colorectal disease with judicious use of CT with oral contrast to detect gross pathology. Patients reporting 'high-risk' symptoms were triaged to qFIT+CT and the remainder underwent an initial qFIT to inform subsequent investigation. Demographic and clinical data were prospectively collected. Outcomes comprised cancer detection frequency. RESULTS: Overall, 422 patients (median age 64 years, 220 women) were triaged using this pathway. Most (84.6%) were referred as 'urgent suspicious of cancer'. Of the 422 patients, 202 (47.9%) were triaged to CT and qFIT, 211 (50.0%) to qFIT only, eight (1.9%) to outpatient clinic and one to colonoscopy. Fifteen (3.6%) declined investigation and seven (1.7%) were deemed unfit. We detected 13 cancers (3.1%), similar to the mean cancer detection rate from all referrals in 2017-2019 (3.3%). Compared with the period 1 April-31 May in 2017-2019, we observed a 43% reduction in all primary care referrals (1071 referrals expected reducing to 609). CONCLUSION: This COVID-adapted pathway mitigated the adverse effects on diagnostic capacity and detected cancer at the expected rate within those referred. However, the overall reduction in the number of referrals was substantial. The described risk-mitigating measures could be a useful adjunct whilst standard diagnostic services remain constrained due to the ongoing pandemic.

Qualitative faecal immunochemical tests (FITs) for diagnosing colorectal cancer in patients with histories of rectal bleeding in primary care: a cohort study.

BACKGROUND: Rectal bleeding is considered an alarm symptom for colorectal cancer (CRC) but it is common and mostly caused by benign conditions. Qualitative faecal immunochemical tests (FITs) for occult blood have been used as diagnostic aids for many years in Sweden when CRC is suspected. The study aimed to evaluate the usefulness of FITs requested by primary care physicians for patients with and without histories of rectal bleeding, in the diagnosis of CRC. METHODS: Results of all FITs requested in primary care for symptomatic patients in the Örebro region during 2015 were retrieved. Data on each patient's history of rectal bleeding was gathered from electronic health records. Patients diagnosed with CRC within 2 years were identified from the Swedish Cancer Register. The analysis focused on three-sample FITs, the customary FIT in Sweden. RESULTS: A total of 4232 patients provided three-sample FITs. Information about the presence/absence of rectal bleeding was available for 2027 patients, of which 59 were diagnosed with CRC. For 606 patients with the presence of rectal bleeding, the FIT showed sensitivity 96.2%, specificity 60.2%, positive predictive value 9.8% (95% CI 6.1-13.4) and negative predictive value 99.7% (95% CI 99.2-100) for CRC. For 1421 patients without rectal bleeding, the corresponding figures were 100%, 73.6%, 8.3% (95% CI 5.6-10.9) and 100% (95% CI 99.6-100). CONCLUSION: The diagnostic performance of a qualitative three-sample FIT provided by symptomatic patients in primary care was similar for those with and without a history of rectal bleeding. FITs seem useful for prioritising patients also with rectal bleeding for further investigation.

An assessment of the effect of haemoglobin variants on detection by faecal immunochemical tests.

Background Faecal immunochemical tests (FIT) for haemoglobin (Hb) are being used in the investigation of colorectal cancer. These tests use antibodies raised to the globin moiety of human Hb. Where the globin structure is abnormal or reduced, it is possible that antibody binding, and thus Hb-detection may be affected. Methods Lysates prepared from whole blood samples of patients with known variants were diluted in manufacturer-specific buffer to 10, 100 and 500 µg Hb/g faeces. These samples were analysed on four FIT analysers and the results compared with samples with no known variant present (normal samples). Results The results from this study show that of 20 variants tested, three showed a decrease in detection by all four analysers. These were ß-thalassaemia major and two fetal cord blood samples. Conclusions Of 20 common Hb variants studied, 17 did not affect detection of Hb by the FIT systems tested. Hb variants leading to a reduction in the presence of a globin chain caused a reduction in Hb detection; in such cases, cancers could be missed.

Prospective cohort study of compliance with faecal immunochemical tests for colorectal cancer screening in Hong Kong.

OBJECTIVE: This study aims to examine the rate and determinants of faecal immunochemical test (FIT) compliance over a four-year period among asymptomatic participants in a colorectal cancer (CRC) screening programme in Hong Kong. METHOD: Self-referred screening participants aged between 50 and 70 years who chose FIT for annual screening were followed up for four years (2008-2012). All participants were reminded up to three times yearly for FIT retrieval within two months of the expected screening date. The proportions of screening participants who failed to adhere to annual FIT tests in 1, 2, 3 and 4-years, respectively, after the initial screening uptake were evaluated. The factors associated with non-compliance with FITs in any year were assessed by a binary logistic regression analysis. RESULTS: From 5700 consecutive screening participants, the compliance rates to FIT were 95.1%, 79.9%, 66.2% and 68.4% at years one to four, respectively. The proportions of people missing one, two and three tests were 6.2%, 19.6% and 2.1%, respectively. From multivariate regression analysis, male subjects, younger participants, smokers and those with positive family history of CRC were more likely to be non-compliant. CONCLUSION: Participants identified as at higher risk for screening non-compliance should be especially considered for individual reminders to enhance screening effectiveness.