Guaiac and immunochemical tests for faecal occult blood in colorectal cancer screening.

Seven hundred and eighty-six subjects spontaneously referring to our Center performed two guaiac (Rehydrated Hemoccult II (R.HO), and Hemoccult Sensa (HO S.)), and two immunochemical (OC Hemodia (Hdia) and Hemeselect (Hsel)) faecal occult blood tests on three consecutive faecal determinations. The positivity rates of 3 day R.HO, HO S., Hdia, and Hsel were 4.8%, 5.6%, 8.4% and 11.2% respectively. One hundred and thirty-five of the 150 subjects with at least one positive test completed the diagnostic work-up. Cancer was detected in three subjects and adenomas in 15. Three-day specificity estimates of R.HO, HO S., Hdia and Hsel in the overall series were 96.1%, 96.0%, 93.8% and 91.2% respectively, the differences between guaiac and immunochemical tests being significant. Corresponding values of specificity as determined on the first faecal sample only in the overall series were 98.1%, 98.3%, 96.1% and 94.9% respectively. No significant difference in specificity is evident when 3-day guaiac tests are compared to 1-day immunochemical ones. Three-day immunochemical testing is not recommended for screening purposes due to its very low specificity. Nevertheless, 1-day immunochemical testing is almost as specific as 3-day guaiac testing. A preliminary estimate of colonic neoplasms detection rates shows no difference as well. The benefit of 1-day testing on screening acceptability is evident, but the impact on sensitivity should be evaluated in a screening situation with a proper study design and a larger sample size.     

Immunochemical vs guaiac faecal occult blood tests in a population-based screening programme for colorectal cancer.

Two faecal occult blood tests (FOBTs), Hemoccult II (guaiac based) and Hemeselect (immunochemical) were compared in a population screening for colorectal cancer on 24 282 subjects aged 40-70. Hemeselect was interpreted according to a lower (+ and +/-) and a higher (+) positivity threshold. A total of 8008 compliers were enrolled in the study. Positivity rates: Hemoccult = 6.0%, Hemeselect (+ and +/) = 8.2%, Hemeselect (+) = 3.1%. Among FOBT-positive subject complying with the diagnostic work-up, 22 had colorectal cancer (17 Hemeselect-positive (+), four Hemeselect-borderline (+/-), 15 Hemoccult-positive) and 166 subjects had adenomas (62 Hemeselect(+), 56 Hemeselect-borderline (+/-), 79 Hemoccult-positive) were detected. The positive predictive values (PPVs) for cancer were as follows: Hemoccult = 3.7%, Hemeselect (+ and +/-) = 3.8%, Hemeselect (+) = 8.4%. The PPVs for adenoma(s) were: Hemoccult = 19.7%, Hemeselect (+ and +/-) = 21.4%, Hemeselect (+) = 30.5%. The specificity for cancer was: Hemoccult = 94.1%, Hemeselect (+ +/-) = 92%, Hemeselect (+) = 97.1%. Ratios between detection rates of each test and expected incidence of colorectal cancer suggest that Hemoccult anticipates cancer diagnosis by approximately 2 years on average whereas the mean diagnostic anticipation of Hemeselect ranges between 2.5 and 3.2 years. Hemeselect is superior to Hemoccult as it is at least as effective but more efficient and acceptable than guaiac testing. Further evaluation of Hemeselect cost-effectiveness and sensitivity is needed in order to assess the optimal threshold of positivity and screening frequency.     

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml⁻¹, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml⁻¹, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml⁻¹ provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.     

Comparison and combination of blood-based inflammatory markers with faecal occult blood tests for non-invasive colorectal cancer screening

Background:

Faecal occult blood tests (FOBTs) are widely used for colorectal cancer (CRC) screening. Blood-based inflammatory markers have been suggested as alternative or supplementary non-invasive CRC screening tests.

Methods:

Among 179 CRC patients, 193 people with advanced adenoma and 225 people free of neoplasm, C-reactive protein (CRP), serum CD26 (sCD26), complement C3a anaphylatoxin and tissue inhibitor of metalloproteinases 1 (TIMP-1) levels in blood were measured by ELISA tests, and an immunochemical FOBT (iFOBT) and a guaiac-based FOBT were performed. Receiver operating characteristic curves were constructed and the areas under the curves (AUCs) were compared.

Results:

The blood levels of CRP, sCD26 and TIMP-1 showed statistically significant differences between CRC patients and neoplasm-free participants, and levels of TIMP-1 were furthermore significantly elevated in advanced adenoma patients. For the four inflammatory markers, AUCs ranged from 0.52 to 0.62 for CRC detection and from 0.50 to 0.58 for advanced adenomas detection, compared with AUCs of 0.90 and 0.68 for the iFOBT. At 97% specificity, blood markers showed much lower sensitivities than FOBTs. Combining inflammatory markers with the iFOBT increased the AUC for advanced adenomas.

Conclusion:

These blood-based markers do not seem to be an alternative to FOBT-based CRC screening. The potential use of these and other blood-based tests in combination with iFOBT might deserve further attention.     

Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy

There is increasing evidence that faecal immunochemical tests (FITs) for haemoglobin offer a number of advantages over traditional guaiac based faecal occult blood tests (gFOBTs). However, evidence on diagnostic performance from direct comparisons with colonoscopy findings in all participants in the average risk population is still sparse. We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of the German screening colonoscopy programme. Pre-colonoscopy stool samples and colonoscopy reports were obtained from 2235 participants of screening colonoscopy in 2005–2009. To enhance comparability of diagnostic performance of the various tests, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting the FIT cut-off haemoglobin (Hb) concentrations in such a way that FIT positivity rates equalled the positivity rate of the gFOBT. Colorectal cancer, advanced adenomas and other adenomas were found in 15 (0.7%), 207 (9.3%) and 398 (17.8%) participants. The gFOBT was positive in 111 (5.0%) participants, with sensitivities (specificities) for detecting colorectal cancer, any advanced neoplasm or any neoplasm of 33.3% (95.2%), 8.6% (95.4%) and 5.5% (95.2%). At the same positivity rate, all three FITs outperformed the gFOBT in all indicators. In particular, all sensitivities of FITs were approximately two to three times higher at increased levels of specificity. All differences were statistically significant, except for some of the performance indicators for colorectal cancer. In conclusion, FITs can detect much larger proportions of colorectal neoplasms even if their cut-offs are set to levels that ensure equally low positivity rates as gFOBT.     

Immunochemical testing of individuals positive for guaiac faecal occult blood test in a screening programme for colorectal cancer: an observational study

BACKGROUND: Screening for colorectal cancer by use of guaiac-based faecal occult blood tests (FOBT) reduces disease-specific mortality. However, due to imperfect specificity, about half of individuals positive for guaiac FOBT are negative for neoplasia on colonoscopy. We aimed to assess whether the testing of individuals positive for guaiac FOBT in a screening programme for colorectal cancer by use of a sensitive immunochemical FOBT could select more appropriately those who should receive colonoscopy. METHODS: We invited individuals who were guaiac FOBT positive in the second screening round of a pilot study in Scotland, UK, to give two samples, each from separate stools, for immunochemical FOBT while awaiting colonoscopy. Results were classed as: both samples negative (N/N), one sample negative and one positive (N/P), and both samples positive (P/P); data were assessed for sampling bias. We compared immunochemical findings with those from colonoscopy using odds ratios of positive samples (P/P) versus negative (N/N and N/P). Sensitivity, specificity, and positive and negative likelihood ratios for cancer, and for cancer and high-risk adenomatous polyps were also calculated. FINDINGS: 1486 participants were invited and 801 (54%) sets of duplicate samples were returned. We found no evidence of sampling bias with regard to sex, age, or degree of positivity on guaiac FOBT. Of 800 sets returned with consent and analysed, 173 (22%) were N/N, 129 (16%) were N/P, and 498 (62%) were P/P. Chi2 test showed a highly significant positive correlation between degree of positivity on guaiac FOBT and on immunochemical FOBT (p<0.003). 795 individuals had data for colonoscopy: one (<1%) of 171 N/N participants and one (<1%) of 127 N/P participants had colorectal cancer, compared with 38 (8%) of 497 P/P participants; adenomatous polyps were found in 28 (16%) N/N individuals, 24 (19%) N/P individuals, and 193 (39%) P/P individuals. Normal colonoscopy was less common in the P/P group (85 [17%]) than in the N/N (67 [39%]) and N/P (49 [39%]) groups. The odds ratio for P/P being associated with cancer was 7.57 (95% CI 1.84-31.4) and with high-risk adenomatous polyps was 3.11 (1.86-5.18). Sensitivity of a P/P result for cancer was 95.0% (81.8-99.1), and for cancer and high-risk adenomatous polyps was 90.1% (84.4-94.0); specificity was 39.5% (36.0-43.1) and 47.8% (43.9-51.8), respectively. INTERPRETATION: Immunochemical FOBT for individuals with positive guaiac FOBT could decrease substantially the number of false positives in a screening programme for colorectal cancer.     

Colorectal cancer screening comparing no screening,immunochemical and guaiac fecal occult blood tests: A cost‐effectiveness analysis

Comparability of cost‐effectiveness of colorectal cancer (CRC) screening strategies is limited if heterogeneous study data are combined. We analyzed prospective empirical data from a randomized‐controlled trial to compare cost‐effectiveness of screening with either one round of immunochemical fecal occult blood testing (I‐FOBT; OC‐Sensor®), one round of guaiac FOBT (G‐FOBT; Hemoccult‐II®) or no screening in Dutch aged 50 to 75 years, completed with cancer registry and literature data, from a third‐party payer perspective in a Markov model with first‐ and second‐order Monte Carlo simulation. Costs were measured in Euros (€), effects in life‐years gained, and both were discounted with 3%. Uncertainty surrounding important parameters was analyzed. I‐FOBT dominated the alternatives: after one round of I‐FOBT screening, a hypothetical person would on average gain 0.003 life‐years and save the health care system €27 compared with G‐FOBT and 0.003 life years and €72 compared with no screening. Overall, in 4,460,265 Dutch aged 50–75 years, after one round I‐FOBT screening, 13,400 life‐years and €320 million would have been saved compared with no screening. I‐FOBT also dominated in sensitivity analyses, varying uncertainty surrounding important effect and cost parameters. CRC screening with I‐FOBT dominated G‐FOBT and no screening with or without accounting for uncertainty.     

Cutoff value determines the performance of a semi-quantitative immunochemical faecal occult blood test in a colorectal cancer screening programme

Background:

The cutoff of semi-quantitative immunochemical faecal occult blood tests (iFOBTs) influences colonoscopy referrals and detection rates. We studied the performance of an iFOBT (OC-Sensor) in colorectal cancer (CRC) screening at different cutoffs.

Methods:

Dutch screening participants, 50–75 years of age, with average CRC risk and an iFOBT value ⩾50 ng ml⁻¹ were offered colonoscopy. The detection rate was the percentage of participants with CRC or advanced adenomas (⩾10 mm, ⩾20% villous, high-grade dysplasia). The number needed to scope (NNTScope) was the number of colonoscopies to be carried out to find one person with CRC or advanced adenomas.

Results:

iFOBT values ⩾50 ng ml⁻¹ were detected in 526 of 6157 participants (8.5%) and 428 (81%) underwent colonoscopy. The detection rate for advanced lesions (28 CRC and 161 with advanced adenomas) was 3.1% (95% confidence interval: 2.6–3.5%) and the NNTScope was 2.3. At 75 ng ml⁻¹, the detection rate was 2.7%, the NNTScope was 2.0 and the CRC miss rate compared with 50 ng ml⁻¹ was <5% (N=1). At 100 ng ml⁻¹, the detection rate was 2.4% and the NNTScope was <2. Compared with 50 ng ml⁻¹, up to 200 ng ml⁻¹ CRC miss rates remained at 16% (N=4).

Conclusions:

Cutoffs below the standard 100 ng ml⁻¹ resulted in not only higher detection rates of advanced lesions but also more colonoscopies. With sufficient capacity, 75 ng ml⁻¹ might be advised; if not, up to 200 ng ml⁻¹ CRC miss rates are acceptable compared with the decrease in performed colonoscopies.     

Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy

Background:

Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55–74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55–74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60.

Methods:

A state-transition model was used to estimate costs and outcomes for each screening scenario vs no screening. A third party payer perspective was adopted. Probabilistic sensitivity analyses were undertaken.

Results:

All scenarios would be considered highly cost-effective compared with no screening. The lowest incremental cost-effectiveness ratio (ICER vs no screening €589 per quality-adjusted life-year (QALY) gained) was found for FSIG, followed by FIT (€1696) and gFOBT (€4428); gFOBT was dominated. Compared with FSIG, FIT was associated with greater gains in QALYs and reductions in lifetime cancer incidence and mortality, but was more costly, required considerably more colonoscopies and resulted in more complications. Results were robust to variations in parameter estimates.

Conclusion:

Population-based screening based on FIT is expected to result in greater health gains than a policy of gFOBT (with reflex FIT) or once-only FSIG, but would require significantly more colonoscopy resources and result in more individuals experiencing adverse effects. Weighing these advantages and disadvantages presents a considerable challenge to policy makers.     

Screening for colorectal cancer in Uruguay with an immunochemical faecal occult blood test.

An observational prospective study was carried out in Uruguay to evaluate the feasibility of colorectal cancer screening using immunochemical faecal occult blood tests with no dietary restrictions in an average-risk population. An automated system was used for processing the samples with a cut-off haemoglobin level of 100 ng/ml. Of the 11,734 study participants who received an immunochemical test kit (OC-Hemodia), 10,573 (90.1%) returned samples for screening. The results of 1170 (11.1%) of the responders were positive. Subsequently, colonoscopy was performed on 879 (75.1%) of the participants with a positive test result and showed neoplasia in 330 participants. Fifty four had advanced cancer, 47 had early cancer, 131 had high-risk adenoma and 98 had low-risk adenoma. The detection rates and the positive predictive values were 0.95 and 8.6% for cancer, and 1.24 and 11.2% for high-risk adenoma, respectively. The high compliance and high detection rates for cancer and high-risk adenoma achieved in the colorectal cancer screening programme verifies the feasibility of an immunochemical faecal occult blood test in screening an average-risk population in Uruguay, a country with a small population, but with high morbidity and mortality rates for this disease.     

Advantage of immunochemical fecal occult blood test in screening for colorectal cancer

Colorectal cancer screening is a high public health priority in all industrialized countries. However, the low sensitivity of the common guaiac screening test (Haemoccult II) makes practitioners and public health deciders reluctant to set up national screening program. In recent years, immunochemical tests based on the use of a specific antibody have been found to be more sensitive than the Haemoccult II test. However, for screening purposes, any gain in sensitivity is of interest only if specificity and positive predictive value are satisfactory. As instance, rehydration of the Haemoccult II test prior to lecture can increase sensitivity, but the associated decrease in specificity and positivity predictive value and the high positivity rate render its value in mass screening debatable. Moreover, extra costs, if existing, must be acceptable for the society. Until recently, immunochemical tests costs made it unaffordable in our societies. The arrival of automated reading is likely to remove this obstacle. Moreover it offers the opportunity of positivity cut-off choice. A recent study was conducted in Cotentin (France) to assess the performance of an immunochemical test with an automated reading technique (Magstream 1000) for different haemoglobin content cut-off points. As previous American, Japanese, Chinese and Italian studies, this study suggests that the use of immunochemical tests could lead a substantial gain, in screening sensitivity. Moreover by choosing a higher haemoglobin content as cut-off point (50 ng/ml instead of usual cut-off at 20 ng/ml), a gain in sensitivity can be obtained with a satisfactory specificity (97%) and positivity rate (3%). Considering the increasing number of publications, the use of an immunochemical test with an automated reading technique could improve the prospects for mass-screening for colorectal cancer, since it offers a promising alternative to guaiac tests.     

Prevention of advanced colorectal cancer by screening using the immunochemical faecal occult blood test: a case-control study

To evaluate colorectal cancer screening with faecal occult blood testing (FOBT) in terms of prevention of advanced cancers, we conducted a case-control study in the areas where an annual screening programme with immunochemical FOBT has been offered to all inhabitants aged 40 years or over. Cases were 357 consecutive patients in the study areas clinically diagnosed as having advanced colorectal cancer or a tumour invading the muscularis propriae or deeper, that is, T(2)-T(4) in TNM classification. Three controls were selected for each case matched by gender, age, residential area and exposure status to screening within 1 year before case diagnosis. The odds ratios (ORs) of developing advanced cancer were calculated using conditional logistic regression analyses. The OR for those screened within 3 years before the diagnosis vs those not screened was 0.54 (95% confidence interval (CI) 0.29-0.99). The ORs were lower for rectum than for colon (0.32-0.73 and 0.84-1.18 for rectum and colon, respectively). For those screened within the past 3 years, OR of developing advanced cancer in the rectum was 0.32 ( 95%CI: 0.12-0.84). A screening programme with immunochemical FOBT can be effective for prevention of advanced colorectal cancer. Risk reduction appears to be larger for rectal than for colon cancer.British Journal of Cancer (2003) 89, 23-28. doi:10.1038/sj.bjc.6601002 www.bjcancer.com     

Debate on colorectal cancer screening by faecal occult blood.

We read with great interest the debate on colorectal cancer(CRC) screening in volume 13 issue 1 of the Annals of Oncology[1]. As opinions in the debate are controversial we would liketo contribute to the discussion on the basis of our experience. The criticisms by the majority of the authors involved in thedebate are based on the results of randomised trials that demonstratethe efficacy of guaiac-based faecal occult blood tests (FOBTs).Guaiac testing was the only available method at the time thosetrials started, approximately two decades     

Seasonal variations do not affect the superiority of fecal immunochemical tests over guaiac tests for colorectal cancer screening

The aim of this study was to compare the seasonal variation in performance of a faecal immunochemical test for haemoglobin (FIT) and a guaiac test (gFOBT) for colorectal cancer screening. From June 2009 to May 2011, 18,290 screening participants (50–74 years old) performed OC‐SENSOR quantitative FIT (1 sample) and Hemoccult II gFOBT (3 stool samples with 2 spots/sample). Referral for colonoscopy required a minimum of one positive spot (gFOBT), or a positive FIT [cut‐off 150 ng haemoglobin/mL buffer (i.e. 30 μg haemoglobin/g feces)]. The performance of tests for detection of advanced neoplasia was compared according to seasons using Receiver Operating Characteristics (ROC) curves, at various FIT cut‐off values. The positivity rate of FIT was significantly lower in the summer compared with other seasons (2.3% versus 3.0%, p = 0.03), whilst the positivity rate of gFOBT increased in the autumn (1.8% versus 1.5%, p = 0.11). FIT was clinically more effective than gFOBT over the four season‐specific ROC curves. At the cut‐off concentration used in the study, the season‐specific FIT/gFOBT ratios for true positive rates were: 2.8 (Autumn), 2.5 (Winter), 3.0 (Spring), 3.7 (Summer), and for false positive rates: 1.2 (Autumn), 1.5 (Winter), 1.8 (Spring), 0.9 (Summer). Therefore, in this study with this cut‐off concentration and in spite of lower positivity rate in summer, the seasonal variations of performance of OC‐SENSOR FIT led to improved gain in specificity in the summer, without a decrease in gain in sensitivity compared with gFOBT.     

Impact of time between faecal immunochemical tests in colorectal cancer screening on screening results: A natural experiment

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT₂), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT₁), and time between the two screening rounds. 18 522 individuals with negative FIT₁ who attended FIT₂ were included in this study. 245 AN were detected at FIT₂, of which 34 were CRC. The CRC detection rate at FIT₂ for participants with FIT₁ = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT₁ ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT₁-value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT₁ ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb.     

Comparative screening with a sensitive guaiac and specific immunochemical occult blood test in an endoscopic study

BACKGROUND: HemoccultSENSA (HOS), the sensitive guaiac fecal occult blood test (FOBT) for colorectal neoplasia, is faulted for its low specificity, which might be improved by substituting or adding FlexSure OBT (FS), the immunochemical test for human hemoglobin. (Both tests are manufactured by Beckman-Coulter Inc., Primary Care Diagnostics, Palo Alto, CA.) The authors compared both FOBTs in an endoscopic study to determine which FOBT to recommend for a population-screening program. METHODS: Both FOBTs, without dietary restrictions, were prepared by 1410 screenees or nonbleeding symptomatic patients (3%). All underwent colonoscopy (51.8%) or flexible sigmoidoscopy (if asymptomatic and both FOBTs were negative). RESULTS: HOS sensitivity for significant neoplasia, cancers, or adenomas >/= 1 cm (20 cases) was similar to that of FS (50% vs. 35%, not significant). However, HOS specificity was lower (95% vs. 99%, confidence interval (CIs) 94-96 vs. 98-99, P < 0.05). In those 11 cases in which both HOS and FS were positive, specificity for significant neoplasia was 100% but sensitivity decreased to 25% (less than HOS alone, P < 0.05). HOS was more sensitive than FS for any neoplasia (55 cases), including adenomas < 1 cm (35% vs. 18%, CIs 22-47 vs. 8-28, P < 0.05), but less specific (96% vs. 99%, CIs 95-97 vs. 98-100, P < 0.05). CONCLUSIONS: Guaiac HOS, which does not require dietary restrictions, is significantly more sensitive for any colorectal neoplasm than the immunochemical FS; it identifies more adenomas with a specificity that is low but acceptable for population screening.     

Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location

We investigated variations in sensitivity of an immunochemical (I-FOBT) and a guaiac (G-FOBT) faecal occult blood test according to type and location of lesions in an average-risk 50- to 74-year-old population. Screening for colorectal cancer by both non-rehydrated Haemoccult II G-FOBT and Magstream I-FOBT was proposed to a sample of 20 322 subjects. Of the 1615 subjects with at least one positive test, colonoscopy results were available for 1277. A total of 43 invasive cancers and 270 high-risk adenomas were detected. The gain in sensitivity associated with the I-FOBT was calculated using the ratio of sensitivities (RSN) according to type and location of lesions, and amount of bleeding. The gain in sensitivity by using I-FOBT increased from invasive cancers (RSN=1.48 (1.16–4.59)) to high-risk adenomas (RSN=3.32 (2.70–4.07)), and was inversely related to the amount of bleeding. Among cancers, the gain in sensitivity was confined to rectal cancer (RSN=2.09 (1.36–3.20)) and concerned good prognosis cancers, because they involve less bleeding. Among high-risk adenomas, the gain in sensitivity was similar whatever the location. This study suggests that the gain in sensitivity by using an I-FOBT instead of a G-FOBT greatly depends on the location of lesions and the amount of bleeding. Concerning cancer, the gain seems to be confined to rectal cancer.     

Screening for colorectal cancer: Comparison of perceived test burden of guaiac-based faecal occult blood test,faecal immunochemical test and flexible sigmoidoscopy

BackgroundPerceived burden of colorectal cancer (CRC) screening is an important determinant of participation in subsequent screening rounds and therefore crucial for the effectiveness of a screening programme. This study determined differences in perceived burden and willingness to return for a second screening round among participants of a randomised population-based trial comparing a guaiac-based faecal occult blood test (gFOBT), a faecal immunochemical test (FIT) and flexible sigmoidoscopy (FS) screening.MethodsA representative sample of the Dutch population (aged 50–74 years) was randomised to be invited for gFOBT, FIT and FS screening. A random sample of participants of each group was asked to complete a questionnaire about test burden and willingness to return for CRC screening.ResultsIn total 402/481 (84%) gFOBT, 530/659 (80%) FIT and 852/1124 (76%) FS screenees returned the questionnaire. The test was reported as burdensome by 2.5% of gFOBT, 1.4% of FIT and 12.9% of FS screenees (comparing gFOBT versus FIT p = 0.05; versus FS p < 0.001). In total 94.1% of gFOBT, 94.0% of FIT and 83.8% of FS screenees were willing to attend successive screening rounds (comparing gFOBT versus FIT p = 0.84; versus FS p < 0.001). Women reported more burden during FS screening than men (18.2% versus 7.7%; p < 0.001).ConclusionsFIT slightly outperforms gFOBT with a lower level of reported discomfort and overall burden. Both FOBTs are better accepted than FS screening. All three tests have a high level of acceptance, which may affect uptake of subsequent screening rounds and should be taken into consideration before implementing a CRC screening programme.     

Quantitative fecal immunochemical tests for colorectal cancer screening

Fecal immunochemical tests (FITs) for hemoglobin (Hb) are increasingly used for colorectal cancer (CRC) screening. We aimed to review, summarize and compare reported diagnostic performance of various FITs. PubMed and Web of Science were searched from inception to July 24, 2017. Data on diagnostic performance of quantitative FITs, conducted in colonoscopy‐controlled average‐risk screening populations, were extracted. Summary receiver operating characteristic (ROC) curves were plotted and correlations between thresholds, positivity rates (PRs), sensitivities and specificities were assessed. Seven test brands were investigated across 22 studies. Although reported sensitivities for CRC, advanced adenoma (AA) and any advanced neoplasm (AN) varied widely (ranges: 25–100%, 6–44% and 9–60%, respectively), with specificities for AN ranging from 82% to 99%, the estimates were very close to the respective summary ROC curves whose areas under the curve (95% CI) were 0.905 (0.88–0.94), 0.683 (0.67–0.70) and 0.710 (0.70–0.72) for CRC, AA and AN, respectively. The seemingly large heterogeneity essentially reflected variations in test thresholds (range: 2–82 µg Hb/g feces) and showed moderate correlations with sensitivity (r = ?0.49) and specificity (r = 0.60) for AN. By contrast, observed PRs (range: 1–21%) almost perfectly correlated with sensitivity (r = 0.84) and specificity (r = ?0.94) for AN. The apparent large heterogeneity in diagnostic performance between various FITs can be almost completely overcome by appropriate threshold adjustments. Instead of simply applying the threshold recommended by the manufacturer, screening programs should adjust the threshold to yield a desired PR which is a very good proxy indicator for the specificity and the subsequent colonoscopy workload.