The cost-effectiveness of immunochemical tests for colorectal cancer screening

BackgroundThe optimal immunochemical test to use for generalised mass screening is still under debate in France.AimTo compare the cost and effectiveness in biennial screening for colorectal cancer of fifteen strategies consisting of the three-stool sample un-rehydrated guaiac faecal occult blood test and three immunochemical tests: Magstream, FOB-Gold and OC-Sensor, at different positivity cut-off levels and stool-sample collection.MethodsA Markov model was used to compare these strategies in a general population of 100,000 individuals aged 50–74 over a 20-year period.ResultsImmunochemical tests were efficient strategies compared with guaiac faecal occult blood test. When all 15 strategies were compared with each other, only five of them remained efficient: the one- and two-stool sample Magstream, the one- and two-stool sample FOB-Gold with the 176 ng/mL cut-off, and the two-stool sample OC-Sensor with the 150 ng/mL cut-off. Sensitivity analyses showed that, at an identical price, the one-stool sample OC-Sensor was the most efficient strategy, and outperformed FOB-Gold.ConclusionOne-stool immunochemical testing can be considered a promising alternative to the guaiac faecal occult blood test for colorectal cancer mass screening in the general population. Competition between manufacturers should now be introduced to reduce purchase price differences.     

Fecal immunochemical test accuracy in average-risk colorectal cancer screening

AIM:To assess the fecal immunochemical test(FIT)accuracy for colorectal cancer(CRC)and advanced neoplasia(AN)detection in CRC screening.METHODS:We performed a multicentric,prospective,double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy.Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample(FIT1)and the highest level of both samples(FITmax)using the OC-sensor.Areas under the curve(AUC)for CRC and AN were calculated.The best FIT1and FITmax cut-off values for CRC were determined.At this threshold,number needed to scope(NNS)to detect a CRC and an AN and the cost per lesion detected were calculated.RESULTS:About 779 individuals were included.An AN was found in 97(12.5%)individuals:a CRC in 5(0.6%)and an advanced adenoma(≥10 mm,villous histology or high grade dysplasia)in 92(11.9%)subjects.For CRC diagnosis,FIT1 AUC was 0.96(95%CI:0.95-0.98)and FITmax AUC was 0.95(95%CI:0.93-0.97).For AN,FIT1 and FITmax AUC were similar(0.72,95%CI:0.66-0.78 vs 0.73,95%CI:0.68-0.79,respectively,P=0.34).Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28%and 42%and specificity between 91%and 97%.At the best cut-off point for CRC detection(115 ng/mL),the NNS to detect a CRC were 10.2 and 15.8;and the cost per CRC was 1814€and 2985€on FIT1 and FITmax strategies respectively.At this threshold the sensitivity,NNS and cost per AN detected were 30%,1.76,and 306€,in FIT1 strategy,and 36%,2.26€and 426€,in FITmax strategy,respectively.CONCLUSION:Performing two tests does not improve diagnostic accuracy,but increases cost and NNS to detect a lesion.     

Similar fecal immunochemical test results in screening and referral colorectal cancer

AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.     

Diagnostic accuracy of immunochemical versus guaiac faecal occult blood tests for colorectal cancer screening

Background  

Immunochemical tests show important advantages over chemical-based faecal occult blood tests (FOBT) for colorectal cancer (CRC) screening, but comparison studies are limited. This study was performed to compare the accuracy of a sensitive immunochemical test with the guaiac test for detecting significant neoplasia (advanced adenomas and CRC) in an average-risk population.     

Cost-effectiveness analysis of immunochemical occult blood screening for colorectal cancer among three fecal sampling methods

BACKGROUND/AIMS: To evaluate the optimal sampling times of stool in immunochemical occult blood screening from the viewpoint of the cost-effectiveness. METHODOLOGY: A colorectal cancer screening was conducted in 5 municipalities (Matsumoto, Hata, Yamagata, Asahi, Sakai), Nagano prefecture, Japan in 1996. Each participant received a fecal occult blood test with 3 consecutive days. For the economic assessment of testing methods, the results of the 1st day, those of the 1st and 2nd days and those of the 3 consecutive days were used for a single-day method, a 2-day method, and a 3-day method. The average costs per detection of one cancer patient and diagnostic validity were evaluated among 3 months. RESULTS: The average costs for one cancer case detected were calculated to be $5924 for a single-day method, $6014 for a 2-day method, and $7123 for a 3-day method, respectively. The sensitivity and specificity were calculated to be 58% and 96% for a single-day method, 89% and 95% for a 2-day method, and 100% and 94% for a 3-day method, respectively, indicating a significant difference in the sensitivity between a single-day method and a 2-day as well as a 3-day method (P < 0.05), and in the specificity among 3 testing methods (P < 0.001). CONCLUSIONS: The present analysis suggests that a 2-day collection method is recommended in the immunochemical occult blood screening from the viewpoint of the cost-effectiveness as well as the diagnostic accuracy.     

Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening

Colorectal cancer (CRC) is the second most common cause of cancer deaths in Canadian men and women - accounting for almost 12% of all cancer deaths. In Ontario, it is estimated that 8100 persons were diagnosed with CRC in 2011, and 3250 died from the disease. CRC incidence and mortality rates in Ontario are among the highest in the world. Screening offers the best opportunity to reduce this burden of disease. The present report describes the findings and recommendations of Cancer Care Ontario's Fecal Immunochemical Tests (FIT) Guidelines Expert Panel, which was convened in September 2010 by the Program in Evidence-Based Care. The purpose of the present guideline is to evaluate the existing evidence concerning FIT to inform the decision on how to replace the current guaiac fecal occult blood test with FIT in the Ontario ColonCancerCheck Program. Eleven articles were included in the present guideline, comprising two systematic reviews, five articles reporting on three randomized controlled trials, and reports of four other studies. Additionally, one laboratory study was obtained that reported on several parameters of FIT tests that helped to inform the present recommendation. The performance of FIT is superior to the standard guaiac fecal occult blood test in terms of screening participation rates and the detection of CRC and advanced adenoma. Given greater specimen instability with the use of FIT, a pilot study should be undertaken to determine how to implement the FIT in Ontario.     

Proportional incidence of interval colorectal cancer in a large population-based faecal immunochemical test screening programme

BackgroundThe European guidelines for quality assurance in colorectal cancer (CRC) screening recommend that interval cancer rate be expressed as a proportion of background incidence rate.AimTo determine the crude and adjusted proportional incidence of interval CRC in an Italian regional two-yearly faecal immunochemical test (FIT) screening programme.MethodsThe programme (year of implementation, 2005) is targeted at over 1,000,000 people aged 50–69 years. The test is a one-sample OC-Sensor (Eiken Chemical Co., Tokyo, Japan). The study covered one-third of the regional area. Excerpts of 434,295 eligible negative FIT records dated 2005–2012 from 193,193 subjects were retrieved from the regional CRC screening data warehouse. By 31 December 2013, the cohort accumulated 198,302 man-years and 235,370 woman-years. Interval CRCs were identified by record-linkage with the local population-based cancer registry. Their number was divided by the expected number, estimated with age-period-cohort models, to obtain the proportional incidence.ResultsThe proportional incidence of interval CRC for men and women was, respectively, 0.06 (95% confidence interval (CI), 0.04–0.09) and 0.17 (95% CI, 0.13–0.23) in the first interval year, and 0.21 (95% CI, 0.16–0.26) and 0.28 (95% CI, 0.22–0.36) in the second year.ConclusionsThe results were acceptable and in line with previous studies.     

Evaluation of a card collection-based faecal immunochemical test in screening for colorectal cancer using a two-tier reflex approach

BACKGROUND: The guaiac faecal occult blood test (gFOBT) has been proved as a screening investigation for colorectal cancer, but has disadvantages. Newer faecal immunochemical tests (FITs) have many advantages, but yield higher positivity rates and are expensive. A two-tier reflex follow-up of gFOBT-positive individuals with a FIT before colonoscopy has been advocated as an efficient and effective approach. METHODS: A new simple and stable card collection FIT was evaluated. RESULTS: 1124 individuals who were gFOBT positive were asked to provide samples. 558 individuals participated, 320 refused and 246 did not return samples. No evidence of sampling bias was found. 302 individuals tested FIT negative and 256 tested positive. In the 302 FIT-negative individuals, 2 (0.7%) had cancer and 12 (4.0%) had large or multiple (high-risk) adenomatous polyps. In contrast, of 254 positive individuals, 47 (18.5%) had cancer and 54 (21.3%) had high-risk polyps. 93 (30.8%) of the FIT-negative individuals had a normal colonoscopy, but only 34 (13.4%) of the FIT-positive individuals had no pathology. Sensitivity, specificity, and positive and negative likelihood ratios (and 95% CIs) for cancer were 95.9% (84.8 to 99.3), 59.2% (54.7 to 63.5), 2.35 (2.08 to 2.65) and 0.07 (0.02 to 0.27), and for cancer and high-risk polyps were 87.8% (80.1 to 92.9), 65.3% (60.6 to 69.7), 2.53 (2.19 to 2.93) and 0.19 (0.11 to 0.31), respectively. CONCLUSIONS: A two-tier reflex screening algorithm, in which gFOBT-positive participants are tested with a FIT, is effective in identifying individuals at high risk of significant colorectal neoplasia. This strategy is transferable across different FIT formats. This approach has been adopted for the Scottish Bowel Screening Programme.     

Mass screening for colorectal cancer

A voluntary community colorectal cancer screening project to detect occult blood in the stool of asymptomatic individuals was undertaken; 49,353 Hemoccult^® II kits were distributed. A total of 23,674 completed kits were returned to a central repository and processed (compliance rate, 48 percent); 851 participants had positive results (3.6 percent). Of the 640 who underwent further medical evaluation, 299 participants (46.7 percent) who had adequate follow-up had no evidence of disease. Diverse disease entities were detected in 341 participants, which was 1.4 percent of those enrolled. Forty-one patients (0.17 percent) showed significant findings that included 29 cancers (0.12 percent) and 12 (0.05 percent) noninvasive malignant polyps. Of the cancers, there were 27 colorectal, one nonHodgkin's lymphoma, and one carcinoma of the vocal cord. In addition, 107 patients (0.45 percent) had benign polyps and 193 patients (0.82 percent) had various diseases of the gastrointestinal tract and other medical conditions. The cost of the program was modest and the results conformed to those found in previous screening surveys. The heightened public awareness of testing for colorectal disease and the detection of early lesions justifies the guaiac test screening program for mass survey.     

Options for screening for colorectal cancer

Unlike other types of cancer, there are several options for screening for colorectal cancer (CRC). The most extensively examined method, faecal occult blood testing (FOBT), has been shown, in three large randomized trials, to reduce mortality from CRC by up to 20% if offered biennally and possibly more if offered every year. Recently published data from the US trial suggest that CRC incidence rates are also reduced by up to 20%, but only after 18 years. In this study, the number of positive slides was associated with the positive predictive value both for CRC and adenomas larger than 1 cm, suggesting that the reduction in CRC incidence was caused by the identification and removal of large adenomas. In this respect, this study supports the concept that removing adenomas prevents CRC. More efficient methods of detecting adenomas include the use of colonoscopy or flexible sigmoidoscopy (FS). Considerable evidence exists from case-control and uncontrolled cohort studies to suggest that endoscopic screening by sigmoidoscopy reduces incidence of distal colorectal cancer. However, in the absence of evidence from a randomized trial, several countries have been reluctant to introduce endoscopic screening. Three trialsare currently in progress (in the UK, Italy and the US) to address this issue. Two of these trials are examining the hypothesis that a single FS screen at around age 55-64 might be a cost-effective and acceptable method for reducing CRC incidence rates. Recruitment and screening are now complete in both studies and the first analysis of results on incidence rates is expected in 2004. Colonoscopy screening at 10-year intervals has recently been endorsed in the US on the basis that the reductions in incidence observed with distal CRC screening can be extrapolated to the proximal colon. However, data are lacking and a pilot study for a trial of the acceptability and efficacy of colonoscopy screening is in progress in the US. It has also been suggested that FOBT testing should be used to detect proximal CRC missed by sigmoidoscopy screening, but the small amount of published data suggest that supplementing FS with FOBT offers very little advantage over FS alone. Other forms of CRC screening are under investigation and represent exciting options for the future. Extraction of DNA from stool is now feasible and a number of research groups have shown high sensitivity for CRC using a panel of DNA markers including mutations in k-ras, APC, p53 and BAT26. Data so far indicate that, with the exception of k-ras, these markers are highly specific and therefore represent a significant improvement over FOBT. Whether these tests will replace or supplement existing methods of screening has yet to be determined. It has been suggested that BAT26, which is a marker of microsatellite instability, a feature of proximal sporadic CRC, might be a useful adjunct to sigmoidoscopy screening. Others have suggested that a test for occult blood should be included with the DNA markers to further increase sensitivity. It is not yet known how sensitive these markers are for adenomas--it is only by detecting adenomas that CRC incidence rates can be reduced. A final exciting new option for screening is virtual colonoscopy (VC), which by screening out people without neoplasia allows colonoscopy to be reserved for patients requiring a therapeutic intervention. The sensitivity of VC for large adenomas and CRC appears to be high, although results vary by centre and there is a steep learning curve. Sensitivity for small adenomas is low, but perhaps it is less essential to find such lesions. Some groups have suggested that virtual colonoscopy might be a useful option for investigating patients who test positive with stool-based screening tests. Whichever CRC screening method is finally chosen (and there is no reason why several methods should not ultimately be available), high quality endoscopy resources will always be required to investigate and treat neoplastic lesions detected.     

大肠癌筛查方法研究新进展

大肠癌筛查能够有效降低大肠癌相关发病率及死亡率,现有多种基于人群的大肠癌筛查方法,本文对其筛查方法的研究进展进行概述,并展望未来发展趋势。