Screening for colorectal cancer with immunochemical faecal occult blood tests

Population-based studies have shown that guaiac faecal occult blood testing followed by colonoscopy in case of positivity can reduce colorectal cancer mortality. However these tests have been criticised for their fairly low sensitivity. For this reason attention has been given to alternative tests. The aim of this paper is to review the evidence for screening for colorectal cancer using qualitative immunochemical faecal occult blood tests. For the complete range of tested cut-off values, immunochemical faecal occult blood tests lead to higher diagnostic yield, improved sensitivity and greater participation. The optimal number of samples and the optimal cut-off value has to suit local resources and the acceptability of missed cancers. All economic evaluations, despite some differences between studies, add further arguments to support the opinion that the immunochemical faecal occult blood test is currently the most cost-effective screening test for average-risk populations. These economic evaluations provide strong arguments in favour of the 1-sample strategy. With decreasing the cut-off value similar performances can be achieved with one-compared to two day sampling. Too few data are currently available to accurately compare existing qualitative tests.     

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.     

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.     

The impact of immunochemical faecal occult blood testing on colorectal cancer incidence

BackgroundThe efficacy of colorectal cancer screening based on faecal immunochemical test, in terms of reduction of colorectal cancer incidence, is under debate. In the district of Florence, an organized screening programme based on faecal immunochemical test has been running since the early 1990s. The aim of this study was to compare the risk of developing colorectal cancer for subjects undergoing faecal immunochemical test with those who did not undergo the test in the same period.MethodsTwo cohorts were analyzed: subjects who underwent an initial faecal immunochemical test between 1993 and 1999 (“attenders”), and unscreened residents in the same municipalities invited to perform the faecal immunochemical test in the same period (“non-attenders”). Kaplan–Meier and Cox regression analysis were performed to evaluate the risk of developing colorectal cancer.ResultsThe attenders’ and non-attenders’ cohorts included 6961 and 26,285 subjects, respectively. Cox analysis showed a reduction in colorectal cancer incidence of 22% in the attenders’ compared to the non-attenders’ cohort (hazard ratio = 0.78, 95% Confidence Interval: 0.65–0.93).ConclusionOur results support the hypothesis that screening based on a single faecal immunochemical test every 2 years produces a significant decrease in colorectal cancer incidence after an average follow-up observation period of 11 years.     

Switching from guaiac to immunochemical faecal occult blood test increases participation and diagnostic yield of colorectal cancer screening

BackgroundCompared with the guaiac-faecal occult blood test (gFOBT), faecal immunological tests (FIT) are considered to be more effective for colorectal cancer (CRC) screening. However, only scarce research has examined the outcomes of switching to FIT within a mature gFOBT-based CRC screening programme.MethodsWe reported a 15-year experience of biennial FOBT screening in a well-defined population of approximately one million inhabitants, including six gFOBT-based screening rounds and one round with FIT at the 30 μg Hb/g cut-off. The main outcome measures were screening participation, FOBT positivity and advanced neoplasia detection in each round.ResultsIn this study, 647 676 screenings were performed in 228 716 different individuals, leading to 17 819 positives and 16 580 follow-up colonoscopies. Compared with the last gFOBT round, switching to FIT led to an increased participation of nearly 20% points, and a fivefold increased detection of CRC and advanced adenoma among invitees (3-fold among attendees). The numbers needed to screen and scope to detect one advanced neoplasia declined from 221 to 66 and from 4.7 to 2.6, respectively.ConclusionsThe present population-based study demonstrated a dramatical increase in the diagnostic yield of advanced neoplasia by switching to FIT within a mature gFOBT-based CRC screening programme.     

Feasibility study of colorectal cancer screening by immunochemical faecal occult blood testing: results in a northern Italian community

AIM: Screening by means of faecal occult blood testing (FOBT) has proved to be effective in reducing colorectal cancer incidence and mortality. We performed a pilot screening for colorectal cancer by latex immunological FOBT in two municipalities of the region Valle d'Aosta, Italy, focusing on problems and obtaining indications for the feasibility and extension of the screening programme on a regional basis. METHODS: A total of 2961 subjects aged 50-74 years were invited by mail to perform a one-day immunochemical FOBT without any dietary restrictions and with a positive threshold put at 100 ng/ml. Patients with positive tests were then invited to undergo colonoscopy and double-contrast barium enema if colonoscopy was incomplete. RESULTS: A total of 1631 subjects performed the screening test with an overall compliance of 55.1%. Seventy-two subjects had a positive FOBT. Detection rates for cancer and adenomas were 1.8 per thousand and 16.6 per thousand, respectively. Positive predictive values (PPVs) for cancer and adenomas were 4.5% and 40.3%, respectively. CONCLUSIONS: Screening had an adequate attendance rate and the majority of the indicators were satisfactory. The use of a one-day quantitative latex FOBT with no dietary restrictions, automation of the analytical procedure, and a positive threshold of 100 ng/ml has shown that a programme based on this test is feasible in both organizational and attendance terms. On the basis of this experience, the extension of the screening on a regional basis is suggested.     

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.     

Harms of colonoscopy in a colorectal cancer screening programme with faecal occult blood test: A population-based cohort study

Background and aimsTo assess the harms of colonoscopy in a real world colorectal cancer screening programme with faecal occult blood test.MethodsRetrospective cohort study of all colonoscopies performed in patients aged 50–74 for a positive guaiac-based faecal occult blood test between September 2003 and February 2010 within the screening programme in progress in Alsace (France). Adverse events were recorded through prospective voluntary reporting by gastroenterologists and retrospective postal surveys addressed to persons screened and their general practitioners.ResultsOf 10,277 colonoscopies, 250 adverse events were recorded, 48 (4.7‰, 95% CI 3.4–6.0) of them being moderate or severe, mainly 10 (1.0‰, 95% CI 0.4–1.6) perforations and 31 (3.0‰, 95% CI 2.0–4.1) bleeding. 91.7% of moderate and severe adverse events were the result of a therapeutic procedure. Of 103 serious adverse events, eight (7.8%) were considered preventable. Gastroenterologists reported 52.2% of moderate and severe adverse events. A mild adverse event or an incident was reported in up to 97.0‰ (95% CI 83.2–110.7) colonoscopies.ConclusionThe harms of colonoscopy were underestimated in all randomized controlled trials on colorectal cancer screening with faecal occult blood test. They are greater in a real world programme, estimated at 7.5 major and 100 minor adverse events per 1000 colonoscopies.     

Rehydration of guaiac-based faecal occult blood tests in mass screening for colorectal cancer. An economic perspective

Owing to dehydration during storage, faecal occult blood tests have been found to lose sensitivity; accordingly, test rehydration before development has been advocated, although this practice has yet to be subjected to an economic evaluation. In this paper, the results from two major screening trials in Sweden and England, one using rehydration and the other not, are so evaluated, based on a costing model developed within the English trial. The higher sensitivity resulting from rehydration was found to be accompanied by losses in specificity, such that, although more cancers are detected, the costs of screening and of cancer detection are actually considerably higher under the rehydration regimen than with non-hydration.     

Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population

BACKGROUND: The guaiac faecal occult blood test (G-FOBT) is recommended as a screening test for colorectal cancer but its low sensitivity has prevented its use throughout the world. METHODS: We compared the performances of the reference G-FOBT (non-rehydrated Hemoccult II test) and the immunochemical faecal occult blood test (I-FOBT) using different positivity cut-off values in an average risk population sample of 10,673 patients who completed the two tests. Patients with at least one test positive were asked to undergo colonoscopy. RESULTS: Using the usual cut-off point of 20 ng/ml haemoglobin, the gain in sensitivity associated with the use of I-FOBT (50% increase for cancer and 256% increase for high risk adenoma) was balanced by a decrease in specificity. The number of extra false positive results associated with the detection of one extra advanced neoplasia (cancer or high risk adenoma) was 2.17 (95% confidence interval 1.65-2.85). With a threshold of 50 ng/ml, I-FOBT detected more than twice as many advanced neoplasias as the G-FOBT (ratio of sensitivity = 2.33) without any loss in specificity (ratio of false positive rate = 0.99). With a threshold of 75 ng/ml, associated with a similar positivity rate to G-FOBT (2.4%), the use of I-FOBT allowed a gain in sensitivity of 90% and a decrease in the false positive rate of 33% for advanced neoplasia. CONCLUSIONS: Evidence in favour of the substitution of G-FOBT by I-FOBT is increasing, the gain being more important for high risk adenomas than for cancers. The automated reading technology allows choice of the positivity rate associated with an ideal balance between sensitivity and specificity.     

Short term outcomes of the first round of a pilot colorectal cancer screening programme with guaiac based faecal occult blood test

Objective

To assess both feasibility and short term outcomes of a population based colorectal cancer screening programme using a biennial guaiac based faecal occult blood test (gFOBT).

Method

All participants were invited by mail to take part in a screening programme using a non‐rehydrated gFOBT. The gFOBTs were first provided by general practitioners (GPs) and then directly mailed to individuals who failed to comply after two invitations. The setting was a French administrative district: Haut‐Rhin (710 000 inhabitants). 182 981 residents aged 50–74 years were invited to participate.

Results

19 274 people (10.5%) were excluded from gFOBT screening and 90 706 completed a gFOBT, so that the participation rate was 55.4% of those eligible. 76.5% of the completed gFOBTs were provided by GPs and 15.5% by direct mailing. The gFOBT positivity rate was 3.4%. The positive predictive value was 42.7% for neoplasia (women 30.8%, men 52.5%), 23.6% for advanced adenoma, and 7.6% for cancer. The number of normal colonoscopic procedures (without neoplasia) needed to be performed for each colonoscopy detecting an advanced neoplasia was 1.8, lower in men (1.2) than in women (3.4), and decreasing with age. Detection rates for neoplasia and cancer were 12.8 and 2.3 per 1000 people screened. 206 adenocarcinomas were detected: 47.6% were stage I and 23.8% stage II. The direct cost was estimated at €29.3 per screened person and €13 466 per cancer detected.

Conclusions

Participation and diagnostic yield of controlled trials of gFOBT screening are reproducible in the real world at an acceptable cost through an organised population based programme involving GPs.     

Long-term effect of faecal occult blood screening on incidence and mortality from colorectal cancer

BackgroundSeveral randomized trials have shown a reduction of colorectal cancer mortality by screening using guaiac-based faecal occult blood tests. However, little is known on the long-term effect of screening at the population level in everyday practice.MethodsSmall-sized geographic areas including a total of 91,199 individuals were allocated to either biennal screening using the Hemoccult-II test or no screening. The expected mortality and incidence in the cohort invited to screening was determined using mortality and incidence in the non-screened population.ResultsColorectal cancer mortality was significantly lower in the population invited to screening than in the non-screened population after 11 screening rounds (standardized mortality ratio: 0.87; 0.80–0.94). The standardized mortality ratio remained significant whatever the duration of follow-up. This reduction in colorectal cancer mortality was more pronounced in those who participated in the first screening campaign, who were regular participants in screening rounds (standardized mortality ratio: 0.67; 0.59–0.76). In contrast, colorectal cancer incidence was not different between the screened and non-screened populations (standardized incidence ratio: 1.01; 0.96–1.06).ConclusionOur findings confirm, in the long term, that screening with Hemoccult can reduce colorectal cancer mortality. The data also highlight the benefit of regular participation in screening and the absence of effect of screening on colorectal cancer incidence.