Sensitivity of latex agglutination faecal occult blood test in the Florence District population-based colorectal cancer screening programme

We evaluated the sensitivity for colorectal cancer (CRC) of the latex agglutination test (LAT), an immunochemical test routinely used in the Florence District screening programme since 2000. Sensitivity was calculated by the proportional interval cancer incidence method in a population of 27,503 consecutive subjects screened in 2000-2002, interval cancers being identified by linkage to the Tuscany Cancer Registry files. Sensitivity was calculated overall and by gender, age, time since last negative LAT, CRC site, and rank of screening. Overall 1- and 2-year sensitivity estimates were 80.7 and 71.5%, respectively, suggesting that faecal occult blood testing screening sensitivity may be suboptimal due to testing or programme quality problems. Increasing screening sensitivity might be achieved if the detection rate of advanced adenomas could be increased without unacceptable loss in specificity.     

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.     

The impact of population-based faecal occult blood test screening on colorectal cancer mortality: a matched cohort study

Background:

Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme.

Methods:

Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000–2007) before the roll out of a national programme. All residents (50–69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier.

Results:

There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83–0.99) overall and 0.73 (95% CI 0.65–0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06–1.38).

Conclusion:

There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants.     

Immunochemical faecal occult blood test: number of samples and positivity cutoff. What is the best strategy for colorectal cancer screening?

Immunochemical faecal occult blood tests have shown a greater sensitivity than guaiac test in colorectal cancer screening, but optimal number of samples and cutoff have still to be defined. The aim of this multicentric study was to evaluate the performance of immunochemical-based screening strategies according to different positivity thresholds (80, 100, 120 ng ml⁻¹) and single vs double sampling (one, at least one, or both positive samples) using 1-day sample with cutoff at 100 ng ml⁻¹ as the reference strategy. A total of 20 596 subjects aged 50–69 years were enrolled from Italian population-based screening programmes. Positivity rate was 4.5% for reference strategy and 8.0 and 2.0% for the most sensitive and the most specific strategy, respectively. Cancer detection rate of reference strategy was 2.8‰, and ranged between 2.1 and 3.4‰ in other strategies; reference strategy detected 15.6‰ advanced adenomas (range=10.0–22.5‰). The number needed to scope to find a cancer or an advanced adenoma was lower than 2 (1.5–1.7) for the most specific strategies, whereas it was 2.4–2.7, according to different thresholds, for the most sensitive ones. Different strategies seem to have a greater impact on adenomas rather than on cancer detection rate. The study provides information when deciding screening protocols and to adapt them to local resources.     

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.     

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     

上海市社区居民大肠癌筛查便隐血检测效果分析

背景与目的：上海市为符合条件的居民提供免费的大肠癌筛查服务,通过对上海市居民大肠癌筛查中两次便隐血检测和后续诊断检查结果的分析,评价筛查中两次便隐血检测的效果,为基于人群的疾病筛查项目提供科学依据。方法：筛查的目标人群为50~74岁的上海居民,使用两次免疫法便隐血检测和危险度评估为初筛,初筛阳性者进行肠镜检查。结果：筛查期间,共有809 528人完成了两次便隐血检测,便隐血检测阳性者共有104 953人,其中第一次阳性的人数为47 421人,阳性率为5.9%,第二次阳性的人数为36 462人,阳性率为4.5%,两次阳性的人数为21 070人,阳性率为2.6%。便隐血检测阳性的筛查对象中,有49 339人接受了肠镜检查,肠镜检查顺应性为47.0%。两次阳性的筛查对象的肠镜参与率明显高于单次阳性的筛查对象（P<0.001）。在所有筛查出的大肠癌和癌前期病变中,仅进行一次便隐血检测可以诊断出大肠癌1 200例,占79.5%;发现癌前期病变3 777例,占68.1%。进行第二次便隐血检测可以多诊断出大肠癌310例,占20.5%;发现癌前期病变1 767例,占31.9%。结论：相比于单次便隐血检测, 进行两次便隐血检测的初筛可以更有效地检测出阳性对象,两次便隐血检测可提高后续肠镜检查的参与率,所检出的大肠癌和癌前期病变数量也均有所提高且增量成本较低。因此建议在以人群为基础的大肠癌筛查中采用两次或更多次数的便隐血检测,以提高筛查效率。     

Performance of immunochemical faecal occult blood test in colorectal cancer screening in average‐risk population according to positivity threshold and number of samples

Immunochemical faecal occult blood tests (I‐FOBT) detect more effectively advanced neoplasia than guaiac tests (G‐FOBT). The study aim was to compare the performance of an I‐FOBT whilst varying the positivity threshold and considering four analysis modalities: one sample was performed (MG₁), two samples were performed and at least one sample was positive (MG₂₊), both samples were positive (MG₂₊₊) or the mean of the two samples' log‐transformed haemoglobin contents exceeded the cutoff (MG_2m). Screening for colorectal cancer using both G‐FOBT and two samples' I‐FOBT was performed by an average‐risk population sample of 20,322 subjects. Among the 1,615 subjects with at least one positive test, 1,277 had a satisfactory colonoscopy result; 43 invasive cancers and 270 high‐risk adenomas were detected. The I‐FOBT was reinterpreted under each analysis modality (a random selection of one sample led to MG₁). For all modalities, increasing the positivity threshold decreased sensitivity and increased specificity. The relative ROC curves (in reference to G‐FOBT) demonstrated similar performance for MG₁ and MG₂₊, and improved performance for MG_2m. MG₂₊₊ sensitivity was limited within the range of positivity thresholds evaluated. For any specificity, MG_2m provided the highest sensitivity. For any sensitivity, MG_2m provided the highest specificity. For any positivity rate, MG_2m provided both the highest sensitivity and specificity. This study suggests the replacement of MG₂₊ by MG₁ or, for even better performance, by MG_2m provided that two samples are performed with similar participation (which should be explored). The targeted positivity rate could then be achieved by choosing the positivity threshold. © 2009 UICC     

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.     

Fecal occult blood screening for colorectal cancer: open issues.

Data from seven case-control and--mainly--three randomized clinical trials consistently indicate that biennial fecal occult blood screening (FOBT) can reduce colorectal cancer (CRC) mortality by approximately 20% after 10-18 years. The reduction may be greater in compliant subjects. In the long-term, incidence also appears to be reduced. There are suggestions that the effect of annual screening may be greater, although data are inadequate to quantify the potential advantages of annual versus biennial screening. The issue of the effectiveness of FOBT in the general population and, more important, of comparative cost-effectiveness with other possible screening tests for CRC, however, remain open to discussion.     

Fecal immunochemical test accuracy in familial risk colorectal cancer screening

There is little information on fecal immunochemical test (FIT) in familial risk colorectal cancer (CRC) screening. Our study assesses FIT accuracy, number needed to scope (NNS) and cost to detect a CRC and an advanced neoplasia (AN) in this setting. We performed a multicentric, prospective, double‐blind study of diagnostic tests on individuals with first‐degree relatives (FDRs) with CRC submitted to screening colonoscopy. Two stool samples were collected and fecal hemoglobin in the first sample (FIT1) and the highest in both samples (FITmax) were determined. Areas under the curve (AUC) for CRC and AN as well as the best FIT1 and FITmax cutoff value for CRC were determined. At this threshold, NNS and the cost per lesion detected were calculated. A total of 595 individuals were included (one FDR > 60 years, 413; two FDR or one ≤ 60 years, 182). AN and CRC were found in 64 (10.8%) and six (1%) patients, respectively. For CRC diagnosis, FIT1 AUC was 0.96 [95% confidence interval (CI): 0.95–0.98] and FITmax AUC was 0.95 (95% CI: 0.93–0.97). For AN diagnosis, FIT1 and FITmax AUC were 0.74 (95% CI: 0.66–0.82). The best cutoff point for CRC was 115. At this threshold, the NNS to detect a CRC was 5.67 and 7.67, and the cost per CRC was 1,064€ and 1591.33€ on FIT1 and FITmax strategies, respectively. FIT shows high accuracy to detect CRC in familial CRC screening. Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.     

False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening

Delayed return of immunochemical fecal occult blood test (iFOBT) samples to a laboratory might cause false negatives because of hemoglobin degradation. Quantitative iFOBT's became increasingly more accepted in colorectal cancer screening. Therefore, we studied the effects of delay between sampling and laboratory delivery on iFOBT performance. IFOBT positivity (≥50 ng/ml hemoglobin) in colorectal cancer screening participants without delay between sampling and laboratory delivery (<5 days), was compared with positivity in participants with ≥5 and ≥7 days delay. Additionally, positive tests were stored at room temperature and retested 5 times within 10–14 days. The sampling date was reported by 61% (n = 3,767) of the participants: in 19% delay was ≥5 days and in 5% ≥7 days. Compared with no‐delay, the adenoma detection rate was already significantly decreased after ≥5 days delay (OR 0.6; 95%CI 0.4–0.9). We retested iFOBT samples of 170 positives of which 139 (82%) had a colonoscopy: 45 (32%) had advanced adenomas (not colorectal cancer) and 8 (6%) had colorectal cancer. Mean daily fecal hemoglobin decrease was 29 ng/ml (S.D. 38 and median 11 ng/ml). In patients with advanced adenomas, hemoglobin in the sample was <50 ng/ml in 5 (11%) 2–3 days after the initial test and in 16 (36%) after 10–14 days. Seven days after the initial test, 2 (25%) colorectal cancer patients became false negative. Both had stage I colorectal cancer and initial values below 100 ng/ml, where the average for stage I is 532 ng/ml. Delay in sample return increased false negative immunochemical FOBT's. Mainly precursor lesions, but also colorectal cancer, will be missed due to delayed sample return. © 2009 UICC     

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.     

To scope or not - the challenges of managing patients with positive fecal occult blood test after recent colonoscopy

BACKGROUNDColorectal cancer (CRC) is a major health problem. There is minimal consensus of the appropriate approach to manage patients with positive immunochemical fecal occult blood test (iFOBT), following a recent colonoscopy.AIMTo determine the prevalence of advanced neoplasia in patients with a positive iFOBT after a recent colonoscopy, and clinical and endoscopic predictors for advanced neoplasia.METHODSThe study recruited iFOBT positive patients who underwent colonoscopy between July 2015 to March 2020. Data collected included demographics, clinical characteristics, previous and current colonoscopy findings. Primary outcome was the prevalence of CRC and advanced neoplasia in a patient with positive iFOBT and previous colonoscopy. Secondary outcomes included identifying any clinical and endoscopic predictors for advanced neoplasia.RESULTSThe study included 1051 patients (male 53.6%; median age 63). Forty-two (4.0%) patients were diagnosed with CRC, 513 (48.8%) with adenoma/sessile serrated lesion (A-SSL) and 257 (24.5%) with advanced A-SSL (AA-SSL). A previous colonoscopy had been performed in 319 (30.3%). In this cohort, four (1.3%) were diagnosed with CRC, 146 (45.8%) with A-SSL and 56 (17.6%) with AA-SSL. Among those who had a colonoscopy within 4 years, none had CRC and 7 had AA-SSL. Of the 732 patients with no prior colonoscopy, there were 38 CRCs (5.2%). Independent predictors for advanced neoplasia were male [odds ratio (OR) = 1.80; 95% confidence interval (CI): 1.35-2.40; P < 0.001), age (OR = 1.04; 95%CI: 1.02-1.06; P < 0.001) and no previous colonoscopy (OR = 2.07; 95%CI: 1.49-2.87; P < 0.001).CONCLUSIONA previous colonoscopy, irrespective of its result, was associated with low prevalence of advanced neoplasia, and if performed within four years of a positive iFOBT result, was protective against CRC.     

Comparative yield and efficiency of strategies based on risk assessment and fecal immunochemical test in colorectal cancer screening: A cross-sectional population-based analysis

ObjectiveIntegration of risk stratification into fecal immunochemical test (FIT) might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer (CRC) screening. A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment (QRA) and FIT, FIT-only and QRA-only strategies in a CRC screening program in China.MethodsThe study included 29,626 individuals aged 40−74 years and invited to participate in a CRC screening program in China. Participants were first invited to undertake QRA and one-time FIT (OC-sensor). Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy. Participation, detection rate, and resource demand for colonoscopy were calculated and compared.ResultsOf the 29,626 invitees, 20,203 completed the parallel combination, 8,592 completed the QRA-only, and 11 completed the FIT-only strategy. For the parallel combination, FIT-only, and QRA-only strategies, the overall positivity rates were 10.2% (2,928/28,806), 5.4% (1,096/20,214), and 6.8% (1,944/28,795), respectively; the yield of advanced neoplasm per 10,000 invitees were 46.9 [95% confidence interval (95% CI): 39.8−55.4], 36.8 (95% CI: 30.5−44.4), and 12.2 (95% CI: 8.8−16.8), respectively; the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7% (95% CI: 4.0%−5.6%), 9.9% (95% CI: 8.3%−11.9%), and 1.9% (95% CI: 1.3%−2.6%), respectively; the number of colonoscopies required to detect one advanced neoplasm was 11.4 (95% CI: 9.8−13.4), 5.7 (95% CI: 4.8−6.7), and 28.4 (95% CI: 20.7−39.2), respectively.ConclusionsThe parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.     

大肠癌筛查方法的研究进展

大肠癌早期筛查可以早期发现大肠癌,遏制其进一步发展,延长预期寿命.其筛查方法主要包括粪便检查、影像学检查、内镜检查和最新的基因检测技术,筛查方法不同,效果也不同.粪便检查是目前最受欢迎的一种筛查方式.