Introduction

In colorectal cancer (CRC) the pathway to diagnosis has rapidly evolved over the past 5 years incorporating Faecal Immunochemical Testing (FIT) as the chosen biomarker in the field. A FIT cut off of ≥10 µg Hb/g faeces is recommended by NICE for investigation of colorectal cancer (CRC) on an urgent pathway based on an expected CRC risk threshold of 3% in England. It is crucial to balance the risk of CRC against the ability of the health service to investigate and diagnose cancer in an appropriate and timely manner.

Aims & Methods

Our aim was to determine the empirical thresholds of CRC risk in a representative population at different FIT cut offs to assess optimal use of FIT in patients with symptoms of CRC. Cohort study of a symptomatic CRC pathway from primary care with a FIT test in Nottingham, UK (November 2017-2021) with 1-year follow-up. Heat maps showed the cumulative 1-year CRC risk using Kaplan-Meier estimates stratified by FIT (fHb <4 µg Hb/g faeces, 4-9.9 µg Hb/g faeces, 10-19.9 µg Hb/g faeces, 20 – 39.9 µg Hb/g faeces, 40- 99.9 µg Hb/g faeces and ≥100 µg Hb/g faeces), age, anaemia (≤130g/l in men; ≤120g/l in women), and thrombocytosis (≥400 x10⁹/l). We estimated the number of investigations that could potentially be re-purposed if a threshold of ≥3% 1-year risk of CRC was instigated.

Results

In total 514 (1.5%) CRC’s were diagnosed following 33694 index FIT tests. Individuals with a FIT ≥10 µg Hb/g faeces had a greater than 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 less than 3%, except those between the age of 70-85 years (CRC risk 5.26% 95% CI 2.72-7.73%). Non-anaemic patients do not meet the 3% threshold set by NICE for investigation until they have a FIT ≥40 µg Hb/g faeces. In contrast, those patients with anaemia meet the 3% threshold at a FIT of ≥20 µg Hb/g faeces. Using a ≥3% CRC threshold in patients < 55 years calculated using FIT, age and anaemia would allow 160-220 colonoscopies per 10000 FIT tests to be re-purposed, at a cost of missing 1-2 CRCs.

Conclusion

CRC risk varies by FIT, age and anaemia when fHb levels are below 100 µg Hb/g faeces. Tailored FIT cut offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold rather than a single cut off of ≥10 µg Hb/g faeces.

Disclosure

none to declare

Introduction

Aims & Methods

Aims: To assess for evidence of association between a symptomatic FIT ≥10μgHb/g and 1 year risk of other GI cancers and influence of age and anaemia on these associations.
Methods: A regional cohort study inclusive of all patients who underwent a symptomatic FIT between 2017-2023 in Nottingham. Heatmaps, stratifying by age group and blood results were constructed to display the cumulative 1-year cancer risks using Kaplan-Meier estimates.

Results

370 (0.54%) out of 68,538 patients were diagnosed with a non-colorectal GI cancer within 1-year of symptomatic FIT. 242/54,855 (0.44%) patients diagnosed with non-colorectal GI cancer had a FIT<10μgHb/g compared to 128/13,683 (0.94%) with a FIT≥10μgHb/g (p<0.0001). A FIT≥10μgHb/g was associated with increased risk of oesophagogastric (p<0.0001) and small bowel (p<0.0001) cancer compared to FIT<10μgHb/g, yet the absolute risks of each were low (<0.5%). There was no association between FIT result and subsequent hepatopancreatobiliary malignancy. When stratified by FIT result, age and blood results the highest risks were seen in patients with anaemia (Table 1). The cumulative risk of small bowel cancer with a FIT≥10μgHb/g in patients under 40 years with anaemia was 0.8% (95%CI: 0-2.35%). The cumulative risk of oesophagogastric cancer with FIT≥10μgHb/g and anaemia in the age group 71-85 was 0.85% (95%CI: 0.49-1.2%).

Conclusion

Introduction

Colorectal cancer (CRC) and other bowel diseases is a significant health concern globally. In several countries, the fecal immunochemical test (FIT) is a cornerstone in CRC screening for early detection of cancer in asymptomatic individuals. Moreover, the utility of FIT extends beyond this, as it is increasingly recommended for evaluating symptomatic patients as part of the clinical pathway to render possible or rule out serious bowel pathology. Therefore, we aimed to quantify the findings of serious bowel conditions following a non-screening FIT test in the Danish population.

Aims & Methods

This study investigated use of FIT beyond the national CRC screening program in Denmark. We aimed (1) to assess utilization patterns of FIT in contexts other than screening and (2) to examine ensuing diagnoses. Our goal was to quantify the findings of CRC and other bowel diseases in symptomatic patients, thereby assessing its broader potential.
This cohort study was conducted within the Danish universal public healthcare system, delivered by five administrative regions. National CRC screening using FIT was initiated in 2014, but utilization of FIT for symptomatic patients varies between regions. The cut-off for a positive test is ≥10 µg haemoglobin/g faeces for symptomatic populations.
The study used data from the Danish Civil Registration System, the Danish National Patient Registry covering all Danish hospitals, and the Clinical Laboratory Information Register. The cohort included all patients who underwent FIT between 2014 and 2021 outside the Danish CRC screening program.
We employed descriptive statistics to examine FIT administration and demographic distributions across the Danish regions, as well as fecal haemoglobin levels among tested individuals. In addition, we estimated the cumulative incidence of CRC and inflammatory bowel disease (IBD) diagnoses following FIT, considering death as a competing risk and evaluated the proportion of diagnoses for CRC and IBD during the year following FIT.

Results

We identified 19,787 individuals who underwent FIT outside the national CRC screening program in 2014 to 2021. Of these, 4,283 (22%) individuals had a positive FIT result. Among tested individuals, 10,807 (55%) were female. Median age at testing was 64 years. Use of FIT varied across the regions, with 36% of the study cohort being from the Central Denmark Region, and 1.6% being from the Region of Southern Denmark.
Positive FIT cases had a shorter median time to CRC diagnosis (28 days) and any diagnosis (36 days) compared to negative FIT cases (711 and 58 days, respectively). Within one year of the FIT, 370 (1.9%) individuals were diagnosed with CRC, with higher occurrence for FIT positive individuals (7.9%) than for FIT negative individuals (0.2%) (risk difference: 7.7 percentage points [95% CI: -3.2, 11.1]).
Among individuals with a positive FIT result, 83 (1.9%) were diagnosed with IBD within one year, compared to 51 (0.3%) individuals with a negative FIT (risk difference: 1.6 percentage points [95% CI: -5.8, 7.3]).

Conclusion

We found that FIT used outside the national CRC screening program had over 20% positivity. A positive test indicated higher risk of CRC and IBD. Differences in diagnoses are expected due to varied follow-up procedures after positive and negative FIT results. A negative test, while not definitive, suggests a potential to rule out disease and could reduce unnecessary investigations when assessing symptomatic patients.

Introduction

The United Kingdom National Institute for Health and Care Excellence recommends Faecal Immunochemical Testing (FIT) for all patients presenting to primary care with symptoms suggestive of colorectal cancer. How use of this test varies across England is unknown, which this study aimed to quantify.

Aims & Methods

Routinely-collected primary care records (Clinical Practice Research Datalink Aurum) were used to assess variations in symptomatic FIT use in adults (≥18 years) between regions and over time in England from 2019 to 2023. Rates were calculated using the population registered to each primary care practice as the denominator, with analysis split by calendar year.
The first coded FIT test with a numerical result per patient each year was extracted from the primary care records. Rates of testing were calculated using Poisson regression, adjusted for other confounders. Results were described between groups, regions and years at the recommended threshold of ≥10 µgHb/g faeces (results above this threshold henceforth referred to as FIT10), describing the proportions likely to have a secondary care referral based on national guidance. Logistic regression was used to compare the impact of year, region, gender and age on the differences in FIT10.

Results

Between 01/01/2019 and 05/06/2023 there were 531,735 FIT results among 495,121 patients and a denominator population of 17,910,681. The number of completed FITs increased from 8,395 in 2019 to 237,708 in 2022 (the last complete year within the study), with a corresponding ~thirty-fold increase from 0.69 tests per 1000 person-years in 2019 (95%CI 0.68-0.71) to 19.57 per thousand person-years in 2022 (95%CI 19.50-19.65). There was large variation in testing between regions, with rates 3.6 times higher in the North East compared to the West Midlands (17.05 per thousand person-years, 95%CI 16.87-17.23 versus 4.72 per thousand person-years, 95%CI 4.67-4.76). These differences persisted to 2022, with less than half the rate in the West Midlands (11.32) compared to the North East (31.85 per thousand person-years).
20.4% of results were FIT10. Despite increased testing, the overall proportion FIT10 did not change over time. 51.7% of all tests FIT10 were in those over 70 years of age. The percentage FIT10 was lower in regions with higher rates of FIT testing, for example FIT10 ranged from 16.7% in the South West (rate of testing 14.62 per thousand person-years) to 25.3% in the South East (rate of testing 8.00 per thousand person-years). After adjusting for year, region, gender and age, this difference persisted (adjusted OR 0.57, 95%CI 0.55-0.58) comparing FIT10 in the South West to the South East. The difference in proportions FIT10 between regions showed some convergence over time, from a range of 16.6%-26.7% (10.1%) in 2021 to 15.8%-23.7% (7.9%) in 2023.

Conclusion

There has been a marked increase over time in the use of FIT for patients with symptoms in primary care, with large and persistent variations between regions of England. The overall proportion FIT10 has not decreased over time with increasing use, however there were large differences in FIT10 between regions that correlated with rates of testing. These regional differences persisted but reduced over time as testing rates increased nationally. It is likely that clinical pathway differences in the implementation of FIT over time and between regions explain the variations we have observed. If used as a guide to referral, such variation could lead to inequalities in colorectal investigation and diagnosis.

Introduction

Colorectal cancer (CRC) screening reduces cancer risk, yet real-world adherence to screening remains variable. We aimed to leverage a large healthcare organization longitudinal cohort to evaluate factors that influence the timeliness of adherence to screening guidelines.

Aims & Methods

We included average-risk Maccabi Healthcare Services members aged 50–75 years who were alive on 1 January 2025. Demographics, comorbidities, hemoglobin values, and dates of fecal immunochemical test(FIT), CT-colonography (CTC) and colonoscopy were extracted.
Adherence was defined as annual FIT, colonoscopy every 10 years, or CTC every 5 years.
Patients covered for >50 % versus ≤50 % of follow-up time by screening guidelines were compared with Wilcoxon rank-sum (continuous) and χ²/Fisher’s exact (categorical) tests.
In order to study factors associated with adherence times, longitudinal adherence was modelled with a gap-time Andersen–Gill Cox regression. The dependent variable was time (in periods) to the recurrent event active adherence. Adjusted hazard ratios (HRs) and 95 % confidence intervals (CI) were estimated with robust variance, clustering on patient ID to account for within-subject correlation.

Results

Our cohort comprised 590,550 adults at screening age, contributing 6,581,044 person-years of follow-up. In a baseline comparison between individuals whose proportion of time covered was less than 50%(n=282,347) vs more than 50%(n=308,203), the latter group was older (60.00 [55.00, 68.00] years vs 62.00 [57.00, 67.00] years, p-value<0.001) with a longer median follow up (9.0 [4.0, 17.0] years vs 11.0 [6.0, 16.0] years, p-value<0.001). Higher prevalence of hypertension (17.5 % vs 12.0 %, p-value<0.001), diabetes mellitus (8.2 % vs 5.8 %, p-value<0.001), pre-diabetes (22.4 % vs 17.5 %, p-value<0.001), and cardiac disease (4.8 % vs 3.4 %, p-value<0.001) were seen among the more compliant group. Consistent with greater adherence, endoscopic referral was more common at baseline in the more compliant group (6.2 % vs 1.0 %, p-value<0.001). Interestingly. Although the differences in distributions of sector, district and socioeconomic rank categories were significant, the absolute percentage differences across strata were small and unremarkable (<3 percentage points for any category).
A gap-time survival model demonstrated that each additional year of age was associated with longer intervals and a lower aHR for active adherence (aHR 0.94, 95 % CI 0.94–0.94). Men undergone screening tests marginally sooner than women (aHR 1.05, 95% CI 1.04–1.05). Adherence was lower in the orthodox sector (aHR 0.84, 95% CI 0.84–0.85). Metabolic or cardiovascular conditions translated into earlier adherence: pre-diabetes (aHR 1.63, 95% CI 1.62-1.63), diabetes (aHR 1.54, 95% CI 1.54-1.55), hypertension (aHR 1.22, 95% CI 1.21-1.23), cardiac disease (aHR 1.14, 95% CI 1.14-1.15), and obesity (aHR 1.10, 95% CI 1.10-1.11). Severe conditions and subjects included in severe disease registry were associated with lower adherence (aHR 0.33, 95% CI 0.30-0.38; and aHR 0.63, 95% CI 0.59-0.67, respectively). Recent higher hemoglobin levels delayed active adherence (aHR 0.97 per each increase of 1 g/dL, 95% CI 0.97-0.98).

Conclusion

Our results suggest that long term compliance for CRC screening is related to age as well as for chronic medical conditions, particularly metabolic and cardiovascular. Screening efforts should therefore be aimed at healthy subjects or those with minor contact with medical providers.

Introduction

Colorectal cancer’s (CRC) incidence above 50 years old has been decreasing globally in the last decades, but its incidence in patients below 50 years old (early-onset colorectal cancer, EO-CRC) has been increasing, for reasons not yet fully understood.

Aims & Methods

A unicentric cohort study was conducted in a tertiary centre, including all patients admitted for a first diagnosis of CRC and evaluated by the Multidisciplinary Colorectal Cancer Group from 01.01.2017 until 31.12.2018. Patients with a previous diagnosis of a Hereditary Colorectal Cancer Syndrome were excluded.

Results

A total of 438 patients were included, 58.2% males, with a mean age at diagnosis of 67.7±11.1 years old. Mean follow-up time was 41.49 months. There were 25 EO-CRC patients (5.7%), 17 males (68%), mean age 43.1±6.0 years old.
Globally, 32.4% of the patients were current or past smokers, 18.5% had previous non-colorectal cancer, 7.5% and 3.4% were previously exposed to immunosuppressive drugs or abdominal/pelvic radiotherapy, respectively. The majority presented with normal(29.7%) to high Body Max Index (39.7%), median 25.6 (IQR:22.6-28.4) Kg/m². The most common CRC location was the rectum (42.9%) and 56.1% were stage I or II (AJCC 8^th edition).
In the univariate analysis, a significant association was found between EO-CRC and: smoking status (past or current smokers 52% in EO-CRC vs. 31.2% in older cases p=0.009); lymphovascular invasion (40.0% in EO-CRC vs. 17.4% in over 50, p=0.018) No significant differences were found for histological subtype (p=0.447), perineural invasion (p=0.474), or tumor stage at diagnosis, although a relevant proportion of the younger patients had metastatic disease at diagnosis (28.0% vs. 12.8%, p=0.064).
Immunohistochemistry for mismatch-repair proteins showed loss of expression of at least one protein in 1/18 EO-CRC patients and 22/179 of older patients (p=0.728).
From the EO-CRC patients, 16 were evaluated in the Familial Cancer Clinic and 14 underwent germline mutation analysis: 13 patients had inconclusive results, one of them presented a MUTYH heterozygote mutation and another was diagnosed with MUTYH-associated Polyposis (composed heterozygote mutation).

Conclusion

Colorectal cancer showed distinctive features in the younger population, with a higher prevalence of lymphovascular invasion and, possibly, a higher incidence of metastatic disease at diagnosis. Smoking had a significant association with CRC, especially in this younger population. Whether this means there is a biological difference is not yet clear. More evidence is needed in order to clarify EO-CRC aetiology and to develop screening and improve management strategies.

References

Siegel RL, Jakubowski CD, Fedewa SA, Davis A, Azad NS. Colorectal Cancer in the Young: Epidemiology, Prevention, Management. Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-14. doi: 10.1200/EDBK_279901. PMID: 32315236

Introduction

In the UK guidance National Institute of Clinical Excellent (NICE) guidance [1] advised early referral for colonoscopy based on symptoms suggesting lower GI malignancy. In June 2022 updated national guidance [2] was published recommending the use of FIT for all community based referral for colonoscopy. A regional FIT testing strategy (cut off 10gHb/g faeces) was implemented from July 2022.

Aims & Methods

To evaluate the outcome of implementing a community based FIT strategy on a regional Health Board colonoscopy service, focussing on diagnostic rates for colorectal cancer (CRC). Data sources included laboratory based FIT registry, EMS endoscopy reporting system and Welsh Clinical Portal (pathology, laboratory, and imaging) for all patients with a community based FIT test between July-December 2022. CRC rates for this cohort were compared with 1) Index Bowel Screening Wales programme patients (aged between 58 and 74 years of age) (referred if FIT result >120 ugHb/g faeces) undergoing colonoscopy in the same time period [n=180], and 2) a historical cohort of symptomatic patients [n=191, 78M:113F, mean age 47.7years, range 18-92] referred for lower GI endoscopy (July-December 2021) when symptom-based referral criteria applied. Differences between the CRC detection rates between each cohort were tested using the Chi-squared test.

Results

A total of 3291 FIT tests were performed (Jul-Dec 2022), 162 were positive (FIT+ rate 4.9%) [89M,73F; mean age 65.7years (range 23-91)]. 48/162 (29.6%) were anaemic. Of the FIT+ cohort 107 underwent colonoscopy and 36 had CT colonography (21 did not complete definitive diagnostic testing). 17/162 (10.4%) had colorectal cancer, with a further 20 (12.3%) have advanced neoplasia. CRC rates increased with increased FIT values: 10-80, 4.8%; 80-120, 11.1%; 120-400, 18%; >400, 25.9%. 107 colonoscopies performed to screen the FIT test cohort detected 16 CRC (14.9% detection rate and were significantly higher than comparator groups attending for colonoscopy; 12/180 (6.7%) in the BSW group [Chi-squared=6.18, d.o.f.1, p<0.025], and 3/191 (1.6%) in the historical symptomatic cohort [Chi-squared=20.65, d.o.f. 1, p<0.001]. Clinically important incidental pathology was detected in a further 11 patients during the course of their investigative pathway.

Conclusion

A regional community FIT testing strategy has been successfully implemented and supported. This has increased significantly diagnostic yield of CRC at colonoscopy vs previous symptom-based referral and national screening programmes. These benefits must be offset against the additional costs of FIT testing, providing clinical oversight and pathway safety netting and managing incidental pathology detected.

References

1. Suspected cancer: recognition and referral. https://www.nice.org.uk/guidance/ng12 (2015)
2. Monahan KJ et al. Gut 2022;71:1939-1962.