Given a gradient relationship between fecal hemoglobin (f-Hb) concentration and colorectal neoplasia demonstrated previously, using f-Hb-guided interscreening interval has increasingly gained attention in population-based fecal immunological test (FIT), but it is very rare to address how to implement such a precision strategy and whether it can economize the use of FIT and colonoscopy.

To demonstrate the applicability of personalized colorectal cancer (CRC) screening with f-Hb-guided screening intervals to reduce the number of FITs and colonoscopy with as equivalent efficacy as universal biennial screening.

A retrospective cohort study for developing f-Hb-guided precision interscreening interval was conducted using data on a Taiwanese biennial nationwide FIT screening program that enrolled more than 3 million participants aged 50 to 74 years between 2004 and 2014. The cohort was followed up over time until 2019 to ascertain colorectal neoplasia and causes of death. A comparative study was further designed to compare the use of FIT and colonoscopy between the personalized f-Hb-guided group and the universal biennial screening group given the equivalent efficacy of reducing CRC-related outcomes.

A spectrum of f-Hb-guided intervals was determined by using the Poisson regression model given the equivalent efficacy of a universal biennial screening. The use of FIT and colonoscopy for the pragmatic f-Hb-guided interval group was measured compared with the universal biennial screening group. Data analysis was performed from September 2022 to October 2023.

Using data from the 3 500 250 participants (mean [SD] age, 57.8 [6.0] years) enrolled in the Taiwanese biennial nationwide FIT screening program, an incremental increase in baseline f-Hb associated with colorectal neoplasia and CRC mortality consistently was observed. Participants with different f-Hb levels were classified into distinct risk categories. Various screening intervals by different f-Hb levels were recommended. Using the proposed f-Hb-guided screening intervals, it was found that the personalized method was imputed to reduce the number of FIT tests and colonoscopies by 49% and 28%, respectively, compared with the universal biennial screening.

The gradient relationship between f-Hb and colorectal neoplasia and CRC mortality was used to develop personalized FIT screening with f-Hb-guided screening intervals. Such a precision interscreening interval led to the reduced use of FIT test and colonoscopy without compromising the effectiveness of universal biennial screening.

To assess the effect of an incremental increase in faecal haemoglobin (f-Hb) concentration on colorectal cancer (CRC) mortality and all-cause death.

We conducted an observational study of cohorts over time based on two population-based CRC screening programmes.

Two cities of Taiwan.

1233 individuals with CRC (217 prevalent cases and 1016 incident cases) and 2640 with colorectal adenoma (1246 prevalent cases and 1394 incident cases) found in the two cohorts of 59 767 and 125 976 apparently healthy individuals, aged 40 years and above, who had been invited to participate in screening since 2001 and 2003, respectively.

Death from CRC and all-cause death ascertained by following up from the entire two cohorts over time until 2009.

The effect of an incremental increase in f-Hb on the risk for CRC mortality was noted, increasing from a slightly increased risk for the category of f-Hb of 20-49 ng Hb/mL (adjusted HR (aHR)=1.09; 95% CI 0.68 to 1.75) to 11.67 (95% CI 7.71 to 17.66) for the group with f-Hb≥450 ng Hb/mL as compared with the group considered baseline with f-Hb of 1-19 ng Hb/mL (p<0.001). A similar but less marked increasing trend was found for all-cause mortality, aHR increasing from 1.15 (95% CI 1.07 to 1.24) for the group with f-Hb of 20-49 ng Hb/mL to 1.67 (95% CI 1.54 to 2.07) for the group with f-Hb≥450 ng Hb/mL.

We substantiated the impacts of an incremental increase in f-Hb on the risk for death from CRC and all-cause death, consistently showing a significant gradient relationship. Both discoveries suggest that f-Hb may not only make contribution to facilitating individually tailored screening for CRC but also can be used as a significant predictor for life expectancy.

The study aimed to determine whether faecal haemoglobin (Hb) concentration can assist in deciding who with lower abdominal symptoms will benefit from endoscopy.

Faecal Hb concentrations were measured on single samples from 280 patients referred for lower gastrointestinal tract endoscopy from primary care in NHS Tayside who completed a faecal immunochemical test (FIT) for Hb and underwent subsequent endoscopy.

Among 739 invited patients, FIT and endoscopy were completed by 280 (median age 63 (18-84) years; 59.6% women), with a median time between FIT and endoscopy of 9 days. Six (2.1%) participants had cancer, 23 (8.2%) had high-risk adenoma (HRA) (more than three adenomas or any > 1 cm), 31 (11.1%) low-risk adenoma (LRA) and 26 (9.3%) inflammatory bowel disease (IBD) as the most serious diagnosis. Those with cancer had a median faecal Hb of > 1000 ng Hb/ml buffer. Those with cancer + HRA + IBD had a median faecal Hb concentration of 75 ng Hb/ml buffer (95% CI 18-204), which was significantly higher than that of all remaining participants without significant colorectal disease (P < 0.0001). Using a cut-off faecal Hb concentration of 50 ng Hb/ml buffer, negative predictive values of 100.0%, 94.4%, 93.4% and 93.9% were found for cancer, HRA, LRA and IBD. Patients with reasons for referral other than rectal bleeding and family history did not have high faecal Hb concentrations.

Faecal Hb concentration measurements have considerable potential to contribute to reducing unnecessary endoscopy for the majority of symptomatic patients.

Guaiac faecal occult blood tests are being replaced by faecal immunochemical tests (FIT). We investigated whether faecal haemoglobin concentration (f-Hb) was related to stage in progression of colorectal neoplasia, studying cancer and adenoma characteristics in an evaluation of quantitative FIT as a first-line screening test.

We invited 66 225 individuals aged 50-74 years to provide one sample of faeces. f-Hb was measured on samples from 38 720 responders. Colonoscopy findings and pathology data were collected on the 943 with f-Hb ≥ 400 ng Hb/ml (80 µg Hb/g faeces).

Of the 814 participants with outcome data (median age: 63 years, range 50-75, 56.4% male), 39 had cancer, 190 high-risk adenoma (HRA, defined as ≥ 3 or any ≥ 10 mm) and 119 low-risk adenoma (LRA). 74.4% of those with cancer had f-Hb>1000 ng Hb/ml compared with 58.4% with HRA, and 44.1% with no pathology. 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 is related to severity of colorectal neoplastic disease. This has ramifications for the selection of the appropriate cut-off concentration adopted for bowel screening programmes.

Guaiac-based faecal occult blood tests (gFOBT) are still used in asymptomatic population bowel screening programmes but are being replaced by faecal immunochemical tests (FIT) for haemoglobin. gFOBT have many well-documented disadvantages and there is little evidence for their use in assessment of the symptomatic. Many laboratories have eliminated gFOBT from their approved repertoires by invoking the authoritative published guidelines. Data continue to accumulate that gFOBT are obsolete. FIT are available in two formats, qualitative and quantitative, the latter having advantages that the faecal haemoglobin concentrations are measured and cut-off concentrations that stimulate further investigation can be user-defined. There is growing evidence that FIT would be useful in a spectrum of clinical settings in addition to screening. All laboratories should have FIT in their existing repertoire. For some uses, qualitative FIT would be adequate. However, much evidence has accumulated that measurements of faecal haemoglobin concentrations are beneficial for the assessment of both disease severity and the future risk of colorectal neoplasia. Interpretation requires appreciation that faecal haemoglobin concentrations are higher in men than women and rise with age. It might well be that risk scoring systems that take gender and age into account, possibly with other factors including symptoms, will benefit individuals. Laboratories should consider how quantitative faecal haemoglobin measurements could be brought into routine practice and included in their forward planning. External quality assessment is needed. Specialists in laboratory medicine are urged to play a significant role in the research and development still required to make this a truly mature investigation.

Fecal immunochemical tests for hemoglobin are replacing traditional guaiac fecal occult blood tests in population screening programs for many reasons. However, the many available fecal immunochemical test devices use a range of sampling methods, differ with regard to hemoglobin stability, and report hemoglobin concentrations in different ways. The methods for sampling, the mass of feces collected, and the volume and characteristics of the buffer used in the sampling device also vary among fecal immunochemical tests, making comparisons of test performance characteristics difficult. Fecal immunochemical test results may be expressed as the hemoglobin concentration in the sampling device buffer and, sometimes, albeit rarely, as the hemoglobin concentration per mass of feces. The current lack of consistency in units for reporting hemoglobin concentration is particularly problematic because apparently similar hemoglobin concentrations obtained with different devices can lead to very different clinical interpretations. Consistent adoption of an internationally accepted method for reporting results would facilitate comparisons of outcomes from these tests. We propose a simple strategy for reporting fecal hemoglobin concentration that will facilitate the comparison of results between fecal immunochemical test devices and across clinical studies. Such reporting is readily achieved by defining the mass of feces sampled and the volume of sample buffer (with confidence intervals) and expressing results as micrograms of hemoglobin per gram of feces. We propose that manufacturers of fecal immunochemical tests provide this information and that the authors of research articles, guidelines, and policy articles, as well as pathology services and regulatory bodies, adopt this metric when reporting fecal immunochemical test results.

Faecal immunochemical tests (FIT) are becoming widely used in colorectal cancer screening. Estimation of faecal haemoglobin concentration in a large group prompted an observational study on gender and age.

A single estimate of faecal haemoglobin concentration was made using quantitative automated immunoturbidimetry. Potential reference intervals were calculated for men and women and for age quintiles according to the Clinical and Laboratory Standards Institute Approved Guideline. The percentages of positive results were calculated at a number of concentrations. The percentages of individuals who fell into different risk groups were assessed.

The 97.5 percentiles, potential upper reference limits, were 519 ng haemoglobin/mL (90% CI: 468-575) for men and 283 ng haemoglobin/mL (90% CI: 257-316) for women. Concentrations increased with age in both genders. Decision limits have advantages over reference intervals. At any cut-off concentration, more men are declared positive than women and more older people are declared positive than younger people. Future risk of neoplasia is higher in men than in women and in older people.

Faecal haemoglobin concentrations vary with gender and age. More tailored strategies are needed in screening programmes. Faecal haemoglobin concentration could be included in individual risk assessment scores. These data should assist in screening programme design.