Implementing Faecal Immunochemical Testing in Primary Care.

Aim: The incidence of colorectal cancer (CRC) has increased globally, in particular patients under the age of fifty. This is a pilot study of a faecal immunochemical testing(FIT) service in primary care. The aim was to trial a FIT service for asymptomatic patients. Methods: We offered FIT kits to asymptomatic patients, aged between 40-75 years old during routine consultations. The number of FITs performed and the outcomes were reviewed. A cut-off of >10µg Hb/g faeces was defined as a positive result. Results: Overall 180 FIT kits were distributed, 7 duplicate tests were given. Of the 173 patients recruited, 142 (82%) samples were analysed in the lab. A total of 126 ( 88.7%) samples had a normal result, 8(5%) were rejected, 31 (17.9%) did not send their sample for analysis. A positive result was found in 8(5%), of these 6 (75%) underwent colonoscopy. No cancer was identified, 4 (50%) had polyps removed and 2 patients require follow up colonoscopy. Discussion: This study represents the first successful implementation of a FIT service in primary care in Ireland. There is a significant unmet need in this setting and strong scientific rationale for the use of FIT testing in general practice.

Colorectal cancer prevalence in faecal immunochemical test non-returners: potential for health inequality in symptomatic referral pathways.

BACKGROUND: This study aimed to describe the faecal immunochemical test non-return rate of those referred with high-risk symptoms of colorectal cancer from primary care, and the clinical outcomes of the 'non-returners'. METHODS: From January 2019 to July 2021, patients referred to secondary care with symptoms suspicious of colorectal cancer and a referral priority of urgent or urgent suspicion of cancer were sent a faecal immunochemical test. All patients were investigated regardless of faecal immunochemical test return or result. Demographics and clinical outcomes such as colorectal cancer prevalence were compared between those who returned a faecal immunochemical test and non-returners. RESULTS: Of 7345 patients included in the study, 874 (11.9%) did not return a faecal immunochemical test. Non-returner characteristics included male sex (P = 0.040), younger age (median age 57 versus 65 years, P < 0.001), per rectal bleeding (P < 0.001) and lower socioeconomic status (median Scottish Index of Multiple Deprivation, 6 versus 7, P < 0.001) compared with those who returned a faecal immunochemical test. Of 6294 patients undergoing colorectal investigation, there was a greater prevalence of colorectal cancer (5.4% versus 3.6% P = 0.032) and significant bowel pathology than in the non-returners (15.3% versus 9.8%, P < 0.001). With a median follow-up of 25 months, the colorectal cancer prevalence for the entire 7345 cohort was equal between those who returned and did not return a faecal immunochemical test (3.2% versus 3.8%, P = 0.108). Of note, the non-returners diagnosed with colorectal cancer were younger (median age 64 versus 73 years, P < 0.001) and from a lower socioeconomic area (median Scottish Index of Multiple Deprivation 4 versus 7, P = 0.015) than faecal immunochemical test returners. CONCLUSION: Patients referred to secondary care, with symptoms suspicious of colorectal cancer, that did not return a faecal immunochemical test had a similar colorectal cancer prevalence to those that returned the test.

Contribution of Fecal Calprotectin and Fecal Immunochemical Tests to the Evaluation of Patients with Ulcerative Colitis.

Cite this article as: Yakut A. Contribution of fecal calprotectin and fecal immunochemical tests to the evaluation of patients with ulcerative colitis. Turk J Gastroenterol. 2024;35(6):509-510.

RE: Contribution of Fecal Calprotectin and Fecal Immunochemical Tests to the Evaluation of Patients with Ulcerative Colitis.

Cite this article as: Hu T, Zhang Z, Song F, Zhang W, Yang J. RE: Contribution of fecal calprotectin and fecal immunochemical tests to the evaluation of patients with ulcerative colitis. Turk J Gastroenterol. 2024;35(6):511.

Faecal immunochemical tests can improve colonoscopy triage in patients with iron deficiency: A systematic review and meta-analysis.

BACKGROUND: Use of the faecal immunochemical test (FIT) to triage patients with iron deficiency (ID) for colonoscopy due to suspected colorectal cancer (CRC) may improve distribution of colonoscopic resources. We reviewed the diagnostic performance of FIT for detecting advanced colorectal neoplasia, including CRC and advanced pre-cancerous neoplasia (APCN), in patients with ID, with or without anaemia. METHODS: We performed a systematic review of three databases for studies comprising of patients with ID, with or without anaemia, completing a quantitative FIT within six months prior to colonoscopy, where test performance was compared against the reference standard colonoscopy. Random effects meta-analyses determined the diagnostic performance of FIT for advanced colorectal neoplasia. RESULTS: Nine studies were included on a total of n=1761 patients with ID, reporting FIT positivity thresholds between 4-150 µg haemoglobin/g faeces. Only one study included a non-anaemic ID (NAID) cohort. FIT detected CRC and APCN in ID patients with 90.7 % and 49.3 % sensitivity, and 81.0 % and 82.4 % specificity, respectively. FIT was 88.0 % sensitive and 83.4 % specific for CRC in patients with ID anaemia at a FIT positivity threshold of 10 µg haemoglobin/g faeces. CONCLUSIONS: FIT shows high sensitivity for advanced colorectal neoplasia and may be used to triage those with ID anaemia where colonoscopic resources are limited, enabling those at higher risk of CRC to be prioritised for colonoscopy. There is a need for further research investigating the diagnostic performance of FIT in NAID patients.

The impact of primary-care led, faecal immunochemical test-based, triage of new-onset colorectal symptoms on time to diagnosis of colorectal cancer-An observational study.

AIM: Since December 2015, a faecal immunochemical test (FIT) has been provided to primary care in NHS Tayside as an adjunct to clinical acumen in the assessment of new-onset bowel symptoms. The aim of this work was to assess the impact of this approach on time to diagnosis of colorectal cancer (CRC). METHOD: NHS Tayside Cancer audit data from January 2013 to December 2019 were reviewed to identify all CRC patients diagnosed via the primary-care referral pathway for a period before and after the introduction of FIT. Their electronic patient records were accessed and date of referral and any contemporaneous FIT and full blood count (FBC) result were recorded. Time from referral to diagnosis of CRC was calculated for each patient and compared between subgroups. RESULTS: The study cohort consisted of 959 patients: 378 and 581 from the time periods before and after the introduction of FIT, respectively. The median time to diagnosis before FIT was 30 days [interquartile range (IQR) 16-57 days] versus 25 days (IQR 14-47 days) following the introduction of FIT (p = 0.006). Following the introduction of FIT, patients who completed a FIT had a median of time to diagnosis of 23 days (IQR 14-43 days) compared with 30 days (IQR 16-62 days) for patients not completing a FIT (p = 0.019). FBC results were available for 97.5% of FIT patients to aid safety-netting of patients with a low or undetectable faecal haemoglobin concentration. CONCLUSION: The introduction of FIT-based triage of new bowel symptoms in primary care as an adjunct to clinical acumen is associated with a reduced time to CRC diagnosis.

Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: inequities in diagnostic yield.

BACKGROUND: Socioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on inequities in health gain remain unclear. METHODS: Sixty-year-olds were randomly recruited from the Swedish population between March 2014 and March 2020 and invited to undergo either 2 rounds of fecal immunochemical testing (FIT) 2 years apart (n = 60 137) or primary colonoscopy just once (n = 30 400). By linkage to Statistics Sweden's registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia in each screening arm (intention-to-screen analysis). In the biennial FIT arm, we predicted the probability of exceeding the yield in the primary colonoscopy arm by linear extrapolation of the cumulative yield to (hypothetical) additional rounds of FIT. RESULTS: In the lowest income group, the yield of advanced neoplasia was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after 2 rounds of FIT vs 1.93% (95% CI = 1.49% to 2.40%) in the primary colonoscopy arm. Extrapolation to a third round of FIT implied a 86% probability of exceeding the yield in the primary colonoscopy arm. In the highest income group, we found a more pronounced yield gap between the 2 screening strategies-2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%)- implying a low (2%) predicted probability of exceeding yield after a third round of FIT. CONCLUSIONS: Yield of advanced neoplasia from 2 rounds of FIT 2 years apart was poorer as compared with primary colonoscopy, but the difference was less in lower socioeconomic groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02078804.

Modelling the impact of bias in fecal immunochemical testing on long-term outcomes of colorectal cancer screening.

BACKGROUND: As the impact of unmanaged bias (i.e. systematic source of inaccuracy) in fecal immunochemical test (FIT) analytical performance on long-term colorectal cancer (CRC) outcomes is unknown, we assessed the impact bias in FIT performance in an ongoing FIT-based CRC screening program. METHODS: This study consisted of two parts: cross-sectional observational data analysis to estimate change in short-term outcomes and microsimulation modelling to estimate change in long-term outcomes assuming different levels of bias by assuming 15 % lower up to 15 % higher Hemoglobin detected in the stool compared to observed. Two scenarios were considered: bias occurring 1) one-time only, due to the occasional bias associated with the FIT kits used in 2020 and 2) consistently due to a constant bias associated with the FIT kits used from 2020 onwards. RESULTS: With a hypothetical bias of -15 % to +15 %, we observed a positivity rate ranging from 6.7 % to 7.8 %, and a detection rate for CRC between 0.65 % and 0.68 %. Single biases in FIT performance resulted in less than 0.1 % change in long-term CRC screening outcomes, while consistent biases resulted in a much larger change (up to 1.4 % in CRC cases and CRC-related deaths and up to 2.07 % in total costs). Detecting lower Hemoglobin concentrations resulted in a relatively larger change on long-term CRC outcomes in comparison to positive bias. CONCLUSIONS: Because of the substantial impact of consistent FIT bias, it is important to set evidence-based acceptance criteria of bias on long-term CRC screening outcomes and in particular, the introduction of an asymmetrical or upward shifted tolerance interval for FIT bias.

Colonoscopy findings after increasing two-stool faecal immunochemical test (FIT) cut-off: Cross-sectional analysis of the SCREESCO randomized trial.

BACKGROUND: We determined the impact of an increased two-stool faecal immunochemical test (FIT) cut-off on colonoscopy positivity and relative sensitivity and specificity in the randomized controlled screening trial screening of Swedish colons conducted in Sweden. METHODS: We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a faecal haemoglobin concentration of at least 10 µg/g in at least one of two stool samples and who underwent a colonoscopy (n = 3841). For each increase in cut-off, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cut-off 10 µg/g. RESULTS: The PPV for AN increased from 23.0% (95% confidence intervals [CI]: 22.3%-23.6%) at cut-off 10 µg/g to 28.8% (95% CI: 27.8%-29.7%) and 33.1% (95% CI: 31.9%-34.4%) at cut-offs 20 and 40 µg/g, respectively, whereas the NNS to find a CRC correspondingly decreased from 41 to 27 and 19. The PPV for AN was higher in men than women at each cut-off, for example 31.5% (95% CI: 30.1%-32.8%) in men and 25.6% (95% CI: 24.3%-27.0%) in women at 20 µg/g. The relative sensitivity and relative specificity were similar in men and women at each cut-off. CONCLUSION: A low cut-off of around 20-40 µg/g allows detection and removal of many AN compared to 10 µg/g while reducing the number of colonoscopies in both men and women.

Faecal Immunochemical Test (FIT) Sensitivity; A Five Year Audit.

Introduction: Colorectal cancer has a high prevalence and mortality rate in the United Kingdom. Cancerous colorectal lesions often bleed into the gastrointestinal lumen. The faecal immunochemical test (FIT) detects haemoglobin (Hb) in the faeces of patients and is used as a first line test in the diagnosis of colorectal cancer. Materials and Methods: A retrospective audit of all FIT performed and all colorectal cancers diagnosed in the Hull and East Riding of Yorkshire counties of the United Kingdom (population approximately 609,300) between 2018 and 2022 was conducted. FIT were performed using a HM-JACKarc analyser from Kyowa medical. The predominant symptom suggestive of colorectal cancer which prompted the FIT was recorded. Colorectal cancer was diagnosed using the gold standard of histological biopsy following colonoscopy. Results: Between 2018 and 2022, 56,202 FIT were performed on symptomatic patients. Follow on testing identified 1,511 with colorectal cancer. Of these people, only 450 people with a confirmed colorectal cancer had a FIT within the 12 months preceding their diagnosis. Of these 450 FIT results, 36 had a concentration of <10 µg/g and may be considered to be a false negative. The sensitivity of FIT in the patients identified was 92.00%. The most common reason stated by the clinician for a FIT being performed in patients with colorectal cancer was a change in bowel habits, followed by iron deficient anaemia. The number of patients diagnosed with colorectal cancer decreased in 2020, but increased significantly in 2021. Discussion: This study shows that 8.00% of people diagnosed with colorectal cancer in the Hull and East Riding of Yorkshire regions had a negative FIT. This study also shows that the SARS-CoV-2 pandemic affected the number of people diagnosed with colorectal cancer, and therefore skews the prevalence and pre-test probability of a positive test. There are many reasons why a FIT could produce a false negative result, the most likely being biological factors affecting the stability of haemoglobin within the gastrointestinal tract, or pre-analytical factors influencing faecal sampling preventing the detection of haemoglobin. Some colorectal lesions do not protrude into the gastrointestinal lumen and are less likely to bleed. Conclusion: This is the first study showing data from outside of a structured clinical trial and provides the largest study to date showing the sensitivity of FIT in a routine clinical setting. This study also provides evidence for the impact COVID-19 had on the rate of colorectal cancer diagnosis.

Lowering Fecal Immunochemical Test Positivity Threshold vs Multitarget Stool RNA Testing for Colorectal Cancer Screening.

This analysis uses data from 2 studies to explore whether lowering the threshold for fecal immunochemical test positivity can achieve comparable levels of sensitivity and specificity as multitarget stool RNA testing for colorectal cancer screening.

Effect of fecal immunochemical test cut-off levels on adenoma detection rate: a systematic review and meta-analysis.

BACKGROUND: Adenoma detection rate (ADR) is higher after a positive fecal immunochemical test (FIT) compared to direct screening colonoscopy. OBJECTIVE: This meta-analysis evaluated how ADR, the rates of advanced adenoma detection (AADR), colorectal cancer detection (CDR), and sessile serrated lesion detection (SSLDR) are affected by different FIT positivity thresholds. METHODS: We searched MEDLINE, EMBASE, CINAHL, and EBM Reviews databases for studies reporting ADR, AADR, CDR, and SSLDR according to different FIT cut-off values in asymptomatic average-risk individuals aged 50-74 years old. Data were stratified according to sex, age, time to colonoscopy, publication year, continent, and FIT kit type. Study quality, heterogeneity, and publication bias were assessed. RESULTS: Overall, 4280 articles were retrieved and fifty-eight studies were included (277,661 FIT-positive colonoscopies; mean cecal intubation 96.3%; mean age 60.8 years; male 52.1%). Mean ADR was 56.1% (95% CI 53.4 - 58.7%), while mean AADR, CDR, and SSLDR were 27.2% (95% CI 24.4 - 30.1%), 5.3% (95% CI 4.7 - 6.0%), and 3.0% (95% CI 1.7 - 4.6%), respectively. For each 20 µg Hb/g increase in FIT cut-off level, ADR increased by 1.54% (95% CI 0.52 - 2.56%, p < 0.01), AADR by 3.90% (95% CI 2.76 - 5.05%, p < 0.01) and CDR by 1.46% (95% CI 0.66 - 2.24%, p < 0.01). Many detection rates were greater amongst males and Europeans. CONCLUSIONS: ADRs in FIT-positive colonoscopies are influenced by the adopted FIT positivity threshold, and identified targets, importantly, proved to be higher than most current societal recommendations.

Stable hemoglobin concentration with fecal immunochemical test at high temperatures in a Caribbean colorectal cancer screening program.

BACKGROUND AND AIMS: High temperatures may reduce fecal immunochemical test (FIT) positivity and colorectal cancer (CRC) detection sensitivity. We investigated the effect of temperature on hemoglobin concentration [Hb], in the FOB Gold®. Additionally, we examined FIT pick-up, storage, return times and specimen collection. MATERIALS AND METHODS: In vitro experiments with buffer containing FIT devices, inoculated with Hb-spiked stool. For 7 days, 144 samples were stored in groups of 36 at 4 °C, 22 °C, 30 °C, and 50 °C. Additionally, 54 samples were stored in groups of 18 at 34 °C, 42 °C and 50 °C for 20 h. Paired t-tests and repeated measure ANOVA assessed [Hb] change. Sixty-five screening participants completed a FIT-handling questionnaire. RESULTS: After 7 days, mean [Hb] was stable at 30 °C (0.8 µg Hb/g;95 %CI: -1.5 to 3.1;p = 0.50). For 50 °C, mean [Hb] decreased within 2 days (-21.3 µg Hb/g;95 %CI: -30.2 to -12.5;p < 0.001) and after 20 h (-63.0 µg Hb/g;95 %CI: -88.7 to -37.3;p < 0.001), respectively. All other temperature categories showed significant mean [Hb] increase. Same-day FIT return was reported by 80 %. Eighty-seven percent experienced specimen collection as easy and 33 % kept the FIT refrigerated after collection. CONCLUSIONS: The FOB Gold® is suitable for CRC screening in tropical climates. Although most respondents indicated same-day sample return, we recommend avoiding FIT storage above 30 °C for longer than7 days.

Immunochemistry-based quantification of tumor-infiltrating lymphocytes and immunoscore as prognostic biomarkers in bladder cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) and the derived immunoscore (IS) have gained considerable attention over the last decade as prognostic markers in many solid cancers. However, in bladder cancer (BC), their prognostic value is not clearly established. METHODS: The present study aimed to quantify the TILs rates in BC, assess the derived immunoscore, and investigate their prognostic value. An immunochemistry-based quantification of the different subtypes of TILS was performed on paraffin-embedded blocks from patients with invasive urothelial carcinoma of the bladder. We have assessed the rates of TILs, respectively, on peri-tumoral (PT) and intra-tumoral (IT) areas and calculated for each case the corresponding IS which is the index: CD8+/CD3+ TILs. The IS was then classified as low (I0, I1) or high (I2, I3, I4). We included 30 cases in the analysis. RESULTS: The median age of patients was 65 years with a sex ratio of 9. TILs densities and distribution were significantly variable between IT and PT areas CD3+ (p = 0.03) and CD8+ (p = 0.004) with the highest rates on the PT areas. In univariate analysis, a low density of CD8+ TILs was significantly associated with an advanced age (p = 0.05), with the presence of lympho-vascular invasion (p = 0.02) and with the absence of specific histological subtype (p = 0.05). A low immunoscore was significantly associated with the presence of lympho-vascular invasion (p = 0.004). No significant association was found between TILs subpopulations, the IS, and the other clinicopathological and survival data. The overall survival (OS) and disease-free survival (DFS) medians were slightly superior in highly T (CD3+/CD8+)-cell infiltrated tumors as well as tumors with a high IS densities. However, the univariate analysis showed that TILs and immunoscore did not impact overall survival (OS) and disease-free survival (DFS). CONCLUSION: TILs and immunoscore might be effective prognostic tools in BC. However, standardized quantification methods and further investigation on larger samples are highly recommended to definitively attest the prognostic value of TILs and IS in BC.

Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening.

BACKGROUND: A next-generation multitarget stool DNA test, including assessments of DNA molecular markers and hemoglobin level, was developed to improve the performance of colorectal cancer screening, primarily with regard to specificity. METHODS: In a prospective study, we evaluated a next-generation multitarget stool DNA test in asymptomatic adults 40 years of age or older who were undergoing screening colonoscopy. The primary outcomes were sensitivity of the test for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions). Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. Secondary objectives included the quantification of sensitivity for advanced precancerous lesions and specificity for nonneoplastic findings or negative colonoscopy and comparison of sensitivities for colorectal cancer and advanced precancerous lesions between the multitarget stool DNA test and a commercially available fecal immunochemical test (FIT). RESULTS: Of 20,176 participants, 98 had colorectal cancer, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy. With the next-generation test, sensitivity for colorectal cancer was 93.9% (95% confidence interval [CI], 87.1 to 97.7), and specificity for advanced neoplasia was 90.6% (95% CI, 90.1 to 91.0). Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3 to 45.6), and specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2 to 93.1). With the FIT, sensitivity was 67.3% (95% CI, 57.1 to 76.5) for colorectal cancer and 23.3% (95% CI, 21.5 to 25.2) for advanced precancerous lesions; specificity was 94.8% (95% CI, 94.4 to 95.1) for advanced neoplasia and 95.7% (95% CI, 95.3 to 96.1) for nonneoplastic findings or negative colonoscopy. As compared with FIT, the next-generation test had superior sensitivity for colorectal cancer (P<0.001) and for advanced precancerous lesions (P<0.001) but had lower specificity for advanced neoplasia (P<0.001). No adverse events occurred. CONCLUSIONS: The next-generation multitarget stool DNA test showed higher sensitivity for colorectal cancer and advanced precancerous lesions than FIT but also showed lower specificity. (Funded by Exact Sciences; BLUE-C ClinicalTrials.gov number, NCT04144738.).

Comparing a fecal immunochemical test and circulating tumor DNA blood test for colorectal cancer screening adherence.

BACKGROUND AND AIM: Colorectal cancer (CRC) screening programs are most effective at reducing disease incidence and mortality through sustained screening participation. A novel blood test modality is being explored for CRC screening, but it is unclear whether it will provide sustained screening participation. This study aimed to investigate whether a circulating tumor DNA (ctDNA) blood test improved CRC screening re-participation when compared with a fecal immunochemical test (FIT) and to define the predictors of sustained CRC screening in an Australian population. METHODS: South Australians who initially participated in CRC screening using a ctDNA blood test (n = 36) or FIT (n = 547) were offered the same CRC screening test approximately 2 years later through an extended phase of a randomized controlled trial. Surveys collected demographic, psychosocial, and clinical information. Predictors of CRC screening re-participation were explored using chi-square, Wilcoxon tests, and logistic regression. RESULTS: Participants offered a second ctDNA blood test were equally likely to re-participate in CRC screening as those who completed a FIT in the first round and who were offered the same test (61% vs 66% re-participation respectively, P = 0.6). CRC fatalism, health activation, and self-efficacy were associated with repeated screening participation. Test awareness was predictive of repeated FIT-based CRC screening. CONCLUSIONS: Targeted interventions to improve CRC screening awareness and increase patient health activation may improve CRC screening adherence. A ctDNA blood test may be a suitable CRC screening option to maintain CRC screening adherence in people who do not participate in screening with FIT.