Anne F. van Rijn

Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population

BACKGROUND & AIMS Despite poor performance, guaiac-based fecal occult blood tests (G-FOBT) are most frequently implemented for colorectal cancer screening. Immunochemical fecal occult blood tests (I-FOBT) are claimed to perform better, without randomized comparison in screening populations. Our aim was to randomly compare G-FOBT with I-FOBT in a screening population. METHODS We conducted a population-based study on a random sample of 20,623 individuals 50-75 years of age, randomized to either G-FOBT (Hemoccult-II) or I-FOBT (OC-Sensor). Tests and invitations were sent together. For I-FOBT, the standard cutoff of 100 ng/ml was used. Positive FOBTs were verified with colonoscopy. Advanced adenomas were defined as >or=10 mm, high-grade dysplasia, or >or=20% villous component. RESULTS There were 10,993 tests returned: 4836 (46.9%) G-FOBTs and 6157 (59.6%) I-FOBTs. The participation rate difference was 12.7% (P < .01). Of G-FOBTs, 117 (2.4%) were positive versus 339 (5.5%) of I-FOBTs. The positivity rate difference was 3.1% (P < .01). Cancer and advanced adenomas were found, respectively, in 11 and 48 of G-FOBTs and in 24 and 121 of I-FOBTs. Differences in positive predictive value for cancer and advanced adenomas and cancer were, respectively, 2.1% (P = .4) and -3.6% (P = .5). Differences in specificities favor G-FOBT and were, respectively, 2.3% (P < .01) and -1.3% (P < .01). Differences in intention-to-screen detection rates favor I-FOBT and were, respectively, 0.1% (P < .05) and 0.9% (P < .01). CONCLUSIONS The number-to-scope to find 1 cancer was comparable between the tests. However, participation and detection rates for advanced adenomas and cancer were significantly higher for I-FOBT. G-FOBT significantly underestimates the prevalence of advanced adenomas and cancer in the screening population compared with I-FOBT.

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 iFOBTs 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 FOBTs. Mainly precursor lesions, but also colorectal cancer, will be missed due to delayed sample return.

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.

Comparison of guaiac and immunological fecal occult blood tests in colorectal cancer screening: the patient perspective.

Abstract Objective. Colorectal cancer (CRC) screening programs can decide upon the type of fecal occult blood test (FOBT): the guaiac FOBT (g-FOBT) or the immunological FOBT (i-FOBT). The effectiveness of any screening program depends not only on the diagnostic performance of the screening test but also on the compliance and general acceptance of the test by the public. Any decision on the type of FOBT for CRC screening should also take acceptation and perception into account. The aim of the present study was to study differences in patient perception between i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups in a population based study. Material and methods. Differences in patient perception of i-FOBT and g-FOBT and differences in perception and participation rates among relevant subgroups were investigated (n = 20,623) by sending a short questionnaire to all invited to the first Dutch CRC screening trial. Results. i-FOBT was perceived significantly more favorable than g-FOBT. About 1275 (32%) participants reported the g-FOBT not easy to use, not easy to perform, disgusting or shameful compared to 742 (16%) for the i-FOBT (p < 0.001). The participation rate was significantly higher in those who received i-FOBT compared to the g-FOBT group: 6159 of 10,322 (60%) versus 4839 of 10,301 (47%) (p < 0.001). Conclusions. These findings support the selection of i-FOBT as the more appropriate test for population screening programs.

Inappropriate use of the faecal occult blood test in a university hospital in the Netherlands.

Objectives Although all international guidelines state that there is no indication to perform a faecal occult blood test (FOBT) in symptomatic patients, we believe the test is frequently used as a diagnostic test. The objective of this study was to investigate whether the current guidelines for FOBT use are being followed in the Netherlands. Methods The frequency of reasons for ordering a FOBT in 15 hospitals over a time period of 1 year was determined and the consequences of the test result on the diagnostic workup were determined by a retrospective search of electronic hospital charts. Results In 14 of the 15 hospitals a FOBT was available and totally 2993 FOBTs were performed in 1 year. A total of 201 electronic charts were retrieved. The FOBTs were ordered because of anaemia (41%), suspicion of rectal bleeding (17%), abdominal pain (14%), changed bowel habits (10%) or others (18%). A positive test result was found in 66 (33%) patients and a negative in 133 (66%). Respectively, 38% (25/66) of the patients with a positive and 41% (55/133) of the patients with a negative test result received a gastrointestinal follow-up investigation. In 25/80 investigations, a possible cause of rectal blood loss was detected, of which 13 had a positive FOBT result. Conclusion This study demonstrates that current guidelines on FOBT use are not followed in the Netherlands and that a FOBT is often used as a diagnostic tool instead of a screening tool, thereby causing confusion and unnecessary delays in the diagnostic workup of patients.

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/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different 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/mL vs 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.

S1125 Differences in Fit Results Between Screening and Referred Colorectal Cancer Patients are Explained by Differences in Tissue Tumor Stage

Background Fecal immunochemical tests (FITs) are state of the art in colorectal cancer(CRC) screening. Sensitivity of a single FIT for advanced neoplasia is around 50%. Theoretically, as blood loss from colon tumors can be intermittent, sensitivity of FITs could improve by double sampling. This study aims to compare the sensitivity of single FIT sampling and double FIT sampling at different cut-off values, for the detection of advanced neoplasia. Methods All subjects (≥18 years) scheduled for elective colonoscopy in three participating centers in the Amsterdam area were asked to perform FITs (OC sensor®) on two consecutive days. FIT results were compared with colonoscopy and histology as gold standard. Test performance of single FIT was compared to the sensitivity of double FIT sampling. Double FIT sampling was considered positive if one of both FITs was higher than the cut-off value. Test performances were evaluated at cut-off values ranging from 50-150ng/ml (incremental steps of 25ng/ml). Results Of 1105 subjects who performed two FITs and underwent total colonoscopy, 140 (9,4%) had advanced neoplasia (AN), of which 34 were CRC and 106 were advanced adenomas (AA). Of the CRC cases, 70% were Dukes stage A or B (stage unknown in 2). Positivity rates for single FIT ranged from 11-17%, and for double FIT from 14-23%. At the same cut-off value for positivity, sensitivity of double FIT sampling was higher than sensitivity of single FIT sampling. For any particular specificity (e.g. 90%), the sensitivity of double FIT was slightly higher than that of single FIT at a lower cut-off value (see table), but these differences were not statistically significant. Conclusions Two fold sampling of FIT does increase sensitivity for advanced neoplasia. However, at a given specificity, sensitivity of double sampling is comparable to single sampling at a lower cutoff value. Sensitivity and specificity of single and double FIT testing for the detection of advanced neoplasia

M1013 a Cost-Effectiveness Analysis in Colorectal Cancer Screening Comparing Immunochemical Faecal Occult Blood Tests with Guaiac Faecal Occult Blood Tests and No Screening.

Introduction: The comparability of cost-effectiveness of colorectal cancer (CRC) screening strategies is limited if heterogeneous study data on tests, populations, and designs are combined. Furthermore cost-effectiveness studies frequently suffer from unrealistic assumptions, e.g. concerning differences in screening participation and adherence to follow-up. Based on empirical data from a representative randomised controlled screening trial with FOBT in the Netherlands (Van Rossum, et al. Gastroenterology 2008), we aimed to compare cost-effectiveness of one round of immunochemical faecal-occult-blood-test (OC-Sensor®, I-FOBT) screening, with one round of guaiac based faecal-occult-blood-test (HemoccultII®, G-FOBT) screening and no screening. Methods: We designed a Markov model of the cost-effectiveness of CRC screening with FOBT and no screening in asymptomatic average risk individuals between 50 and 75 years. From a third-party payer perspective we analysed data with first and second order Monte Carlo simulation over 10 years of one year cycles. Empirical data were completed with cancer registry and literature data. Costs were presented in Euros using a discount rate of 4%. Effects were measured as life years gained using a discount rate of 1.5%. Results: I-FOBT resulted in more life years gained and costs saved (i.e. I-FOBT dominated) compared to G-FOBT and no screening. A hypothetical person invited for colorectal cancer screening with I-FOBT would on average save 0.003 life-years and €5 compared to G-FOBT and compared to no screening 0.006 life-years and €45. Ten years after a single round I-FOBT screening, in the Dutch population aged 50-75 years (n= 4,460,265), 25,200 life-years and €220 million would have been saved compared to no screening. I-FOBT remained the dominant screening strategy in sensitivity analyses when varying colorectal cancer incidence and major cost drivers. Conclusions: CRC screening with I-FOBT dominated G-FOBT and no screening. Accounting for uncertainty surrounding important parameters did not alter this conclusion. Table. Cost-effectiveness according to intention-to-screen analysis of one round immunochemical FOBT screening compared to one round guaiac FOBT screening or no screening