Tiziana Rubeca

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.

Influence of seasonal variations in ambient temperatures on performance of immunochemical faecal occult blood test for colorectal cancer screening: observational study from the Florence district

Background Faecal occult blood testing (FOBT) in population screening has proved to be effective in reducing mortality from colorectal cancer. In Italy a latex agglutination FOBT has been adopted for a single-sample screening programme. The aim of this study was to examine the performance of FOBTs in the Florence screening programme over several seasons to evaluate the impact of variations in ambient temperature on the performance of the screening test. Methods Measured haemoglobin (Hb) concentrations were aggregated into seasons with their average ambient temperature (AAT). Using logistic regression, the AAT over the period preceding the test measurement was analysed. This period included the time between faecal sampling and return of the test sample (mean 7 days) and the time in the laboratory refrigerator before analysis (mean 4 days). The AAT from days 5–11 before analysis of the test sample was considered a determinant of test positivity. The Kruskal–Wallis rank test was used to evaluate the significance of seasonal and/or AAT-related differences in Hb concentration. A logistic regression model adjusted for sex, age, season and screening episode (first or repeated examination) was constructed. Results 199 654 FOBT results were examined. Mean FOBT seasonal Hb concentrations (ng/ml) were: spring 27.6 (95% CI 26.2 to 29.1); summer 25.2 (95% CI 23.1 to 27.3); autumn 29.2 (95% CI 27.7 to 30.6); winter 29.5 (95% CI 27.9 to 31.1). Logistic regression showed that there was a 17% lower probability of the FOBT being positive in summer than in winter. The results of the logistic regression showed that an increase in temperature of 1°C produced a 0.7% reduction in probability of a FOBT being positive. In the summer the probability of detecting a cancer or an advanced adenoma was about 13% lower than in the winter. Conclusions This study showed that there is a significant fall in Hb concentration at higher ambient temperatures. These results will have important implications for the organisation of immunochemical FOBT-based screening programmes, particularly in countries with high ambient temperatures.

Measuring interval cancers in population-based screening using different assays of fecal occult blood testing : The district of florence experience

The fecal occult blood test (FOBT) has demonstrated its efficacy in reducing mortality from colorectal cancer (CRC). The guaiac‐based FOBT has been criticized for its low sensitivity. In this study, two different assays for FOBT (guaiac or an immunochemical test based on reversed passive hemagglutination [RPHA]) were tested for comparison within a population‐based screening program for colorectal cancer in the province of Florence (Italy). The proportional incidence method was used to calculate sensitivity for both FOBTs, according to rank of screening (first or repeat), age at entry (two groups of 50 to 59 and 60 to 70 years old) and lesion site (colon or rectum). When comparing FOBTs, the sensitivity multivariate Poisson regression was used to adjust for other variables. The sensitivity after the first 2 years was 50% (95% confidence interval [CI] 34% to 63%) for the guaiac test versus 82% (95% CI 67% to 92%) for RPHA. At multivariate analysis the risk of developing an interval cancer after a guaiac test is almost 3 times that after RPHA (rate ratio = 2.64; 95% CI 1.3 to 5.4). Our study confirms that RPHA is more sensitive than the guaiac test. The assumption that FOBT screening for CRC has to be based on a guaiac test should be reconsidered, and RPHA should be recommended as the standard FOBT for screening purposes.

Association of FOBT-assessed faecal Hb content with colonic lesions detected in the Florence screening programme.

We assessed the correlation between quantitative results of immunological faecal occult blood testing (I-FOBT) and colonic lesions (191 colorectal cancers, 890 adenomas) detected at colonoscopy in 2597 FOBT+ (cutoff 100 ng ml−1 Hb) subjects. At univariate analysis, a higher average faecal Hb content was significantly associated with male gender (P=0.003), age (P=0.02), and colonoscopy findings (P=0.000). Among adenomas, higher faecal Hb content was significantly associated with size (P=0.0000), presence of severe dysplasia (P=0.0001), presence of villous component (P=0.0002), and location in the left colon (P=0.003). At multivariate analysis adjusting for potential confounders, age (P=0.03), size (P=0.0000), and location in the left colon (P=0.0005) were confirmed as having an independent association with higher faecal Hb content. Immunological FOBT is confirmed to be a specific screening test to detect cancer and adenoma, with a low positivity rate (3.7%) and a high positive predictive value (41.5%). Faecal Hb content is significantly higher for those lesions (cancer and high-risk adenomas) screening is aimed at detecting.

Basic variables at different positivity thresholds of a quantitative immunochemical test for faecal occult blood

OBJECTIVES: Screening by faecal occult blood testing (FOBT) is effective in decreasing mortality and incidence of colorectal cancer (CRC). Immunochemical tests have proved to be more cost effective than guaiac FOBTs. The latex agglutination test (LAT) has the advantage of being a fully automated, quantitative test. The aim of this study is to interpret the overall experience with LAT according to different positivity thresholds. SETTING: A population based screening programme is currently running involving subjects aged 50–70, invited every 2 years to have an FOBT. LAT is the standard screening test and has a positivity threshold for further diagnostic tests of 100 ng haemoglobin/ml of sample solution. METHODS: Positivity rates, detection rates for CRC high risk adenomas, and positive predictive values for CRC, high risk adenomas, and low risk adenomas were calculated for several positivity thresholds. RESULTS: 19 132 attendances at screening were recorded (11 774 at first screening, 7358 at subsequent screenings). Progressively increasing the positivity threshold from 100 to 200 ng/ml showed (a) a decrease in positivity rate; (b) a decrease in detection rates for CRC or high risk adenomas; (c) an increase in positive predictive values for cancer; (d) an increase in positive predictive value for high risk adenomas. CONCLUSIONS: Increasing the positivity threshold of the LAT reduces recall rate and improves positive predictive value for cancer or high risk adenomas but substantially decreases the detection rate of CRC and high risk adenomas. For this reason increasing the positivity cut off for LATs is not advisable. On the other hand decreasing the positivity threshold would increase recall rate and sensitivity of screening. Careful evaluation of sensitivity of the quantitative results of the LAT for interval cancers is needed to definitively assess the optimal positivity threshold for LATs in population based screening programmes.

Screening for colorectal cancer by faecal occult blood test: comparison of immunochemical tests

Objective To compare two immunochemical faecal occult blood tests based on reversed passive haemagglutination (RPHA) or latex agglutination (Hdia) in a population based screening setting. Method Hdia was interpreted according to three positivity thresholds: 100, 150, or 200 ng of haemoglobin/mg of specimen solution. A total of 5844 subjects were recruited into the study, from 17 432 invited subjects aged 50–70. Results Positivity rates were 3.3% for RPHA, Hdia100 3.5%, Hdia150 2.5%, Hdia200 2.0%. Among subjects complying with the diagnostic work up, colorectal cancer (CRC) was detected in 19 subjects (17 RPHA positive, 16 Hdia100 positive, 15 Hdia150 positive, 14 Hdia200 positive) and high risk adenoma/s in 41 subjects (28 RPHA positive, 32 Hdia100 positive, 29 Hdia150 positive, 25 Hdia200 positive). The prevalence of screen positive CRC in the population was for RPHA 2.9‰, Hdia100 2.7‰, Hdia150 2.6‰, Hdia200 2.4‰. The prevalence of screen positive high risk adenomas in the population was for RPHA 4.8‰, Hdia100 5.5‰, Hdia150 5.0‰, Hdia200 4.3‰. Conclusion Hdia100 was as sensitive as RPHA for cancer and high risk adenomas. As Hdia is less technically complex than RPHA, it is a valid alternative to the latter, provided that full automation of the development procedure is available. Increasing the positivity threshold of Hdia up to 150 or 200 ng of haemoglobin/mg of specimen solution is not advisable as the increase in specificity is too small to justify the corresponding decrease in the detection of screen positive cancers in the population.

Faecal haemoglobin concentrations vary with sex and age, but data are not transferable across geography for colorectal cancer screening.

Abstract Background: Faecal immunochemical tests (FIT) are becoming widely used in colorectal cancer (CRC) screening. Availability of data on faecal haemoglobin concentrations (f-Hb) in three countries prompted an observational study on sex and age and the transferability of data across geography. Methods: Single estimates of f-Hb in large groups were made in Scotland, Taiwan and Italy using quantitative automated immunoturbidimetry on the Eiken OC-Sensor. Distributions were examined for men and women overall and in four different age groups. Results: The distributions of f-Hb were not Gaussian and had kurtosis and positive skewness. The distributions were different in the three countries: f-Hb varies with sex and age in all countries, being higher in men and the elderly, but the degree of variation is inconsistent across countries, f-Hb being higher in Scotland than in Taiwan than in Italy, possibly due to different lifestyles. At any cut-off concentration, more men are declared positive than women and more older people are declared positive than younger individuals. Conclusions: Our analysis supports the view that setting and using a single f-Hb cut-off in any CRC screening programme is far from ideal. We suggest that individualisation is the optimum approach with f-Hb, alone or with other important factors such as sex and age, used to determine important personal issues such as need for colonoscopy, screening interval between tests and risk of future CRC. Whether there is merit in monitoring f-Hb in individuals over time remains an interesting research question for the future.

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.

Colorectal cancer screening by fecal occult blood testing: results of a population-based experience.

Aims and background The study evaluated the results of an experimental screening protocol for colorectal cancer by fecal occult blood testing in a municipality of the Province of Florence. Methods A total of 15,235 subjects aged 50–70 years were invited to perform a 1-day immunochemical fecal occult blood testing without any dietary restrictions. All eligible subjects were sent a personal invitation letter, followed by a postal reminder to non-responders. Subjects with a negative stool test were advised to repeat screening after 2 years. Subjects with a positive screening test were invited to undergo full colonoscopy or a combination of left colonoscopy and a double contrast barium enema. Results A total of 6,418 subjects performed the screening test, with an overall compliance of 42.1%. A total of 268 compilers had positive test results. The positivity rate was 4.2%. Detection rate for cancer and for adenomas was 5.1‰ and 11.6‰, respectively. The positive predictive value was 14.3% for cancer and 32.5% for adenoma. A higher compliance was recorded in subjects born in the province of Florence or living in the centre of the town, in married subjects, and in women. The best results in compliance were associated with the direct distribution of fecal occult blood testing kits by general practitioners to their outpatients. Conclusions The study provides useful information about the efficiency and feasibility of a screening program for colorectal cancer using fecal occult blood testing. Compliance results confirm the importance of GP involvement in oncological screening.

Evaluation of diagnostic accuracy of screening by fecal occult blood testing (FOBT). Comparison of FOB Gold and OC Sensor assays in a consecutive prospective screening series

We evaluated a new immunological fecal occult blood testing assay (FOB Gold, Sentinel = SENT) compared to the assay currently employed in the Florence screening program (OC-Hemodia, Eiken = OC). A total of 4,133 subjects were screened with both tests and underwent colonoscopy if positive (100 ng/mL Hb cutoff) to either test: 190 (4.59%) were positive (OC =140 (3.4%); SENT = 131 (3.2%)). The relative sensitivity for 7 cancers was 100% with OC and 67.9% with SENT, and for 48 high-risk adenomas (HRAs) it was 77.0% with OC and 66.6% with SENT. The positive predictive value (PPV) for cancer+HRA was 31.4% for OC and 28.2% for SENT and the specificity was 97.7 for both. The differences were not statistically significant. Adding SENT to OC increased the positivity rate by 32% and the cancer+HRA detection rate by 25%, and decreased the PPV by 10%. Both tests were performed on the same tubes in 1,601 cases, and in 18 of 47 cases they differed on different tubes but not on the same tube, suggesting inhomogeneous Hb content or varying fecal matrix influence in different samples. SENT has practical advantages for screening [corrected] (fully automated, high output, requires no dedicated instrument), a comparable specificity and a lower sensitivity, though the latter difference may be partially ascribed to differences in sampling and not to the assay itself [corrected] Because of the statistical insignificance of the differences, further studies are needed for confirmation.