Seasonal variations do not affect the superiority of fecal immunochemical tests over guaiac tests for colorectal cancer screening.

The aim of this study was to compare the seasonal variation in performance of a faecal immunochemical test for haemoglobin (FIT) and a guaiac test (gFOBT) for colorectal cancer screening. From June 2009 to May 2011, 18,290 screening participants (50-74 years old) performed OC-SENSOR quantitative FIT (1 sample) and Hemoccult II gFOBT (3 stool samples with 2 spots/sample). Referral for colonoscopy required a minimum of one positive spot (gFOBT), or a positive FIT [cut-off 150 ng haemoglobin/mL buffer (i.e. 30 µg haemoglobin/g feces)]. The performance of tests for detection of advanced neoplasia was compared according to seasons using Receiver Operating Characteristics (ROC) curves, at various FIT cut-off values. The positivity rate of FIT was significantly lower in the summer compared with other seasons (2.3% versus 3.0%, p = 0.03), whilst the positivity rate of gFOBT increased in the autumn (1.8% versus 1.5%, p = 0.11). FIT was clinically more effective than gFOBT over the four season-specific ROC curves. At the cut-off concentration used in the study, the season-specific FIT/gFOBT ratios for true positive rates were: 2.8 (Autumn), 2.5 (Winter), 3.0 (Spring), 3.7 (Summer), and for false positive rates: 1.2 (Autumn), 1.5 (Winter), 1.8 (Spring), 0.9 (Summer). Therefore, in this study with this cut-off concentration and in spite of lower positivity rate in summer, the seasonal variations of performance of OC-SENSOR FIT led to improved gain in specificity in the summer, without a decrease in gain in sensitivity compared with gFOBT.

A population-based comparison of immunochemical fecal occult blood tests for colorectal cancer screening.

BACKGROUND & AIMS: Quantitative fecal immunochemical tests (FITs) identify individuals with colorectal cancer with greater levels of accuracy than guaiac tests. We compared the performances of 2 FITs in a population undergoing screening for colorectal cancer. METHODS: We collected fecal samples from 19,797 individuals in France (age, 50-74 y) who participated in a colorectal cancer screening program, from June 2009 through May 2011. Samples were analyzed using the Magstream (Fujirebio Inc, Tokyo, Japan) and OC Sensor (Eiken Chemical Co, Tokyo, Japan) (2 samples each) FITs, as well as the Hemoccult II guaiac test (SKD, Villepinte, France) (3 samples each). Colonoscopies were performed for patients with positive results from all 3 tests. The cut-off values for levels of hemoglobin in buffer and stools were 55 ng/mL and 180 µg/g for the Magstream and 150 ng/mL and 30 µg/g for the OC Sensor, respectively. Results from the FITs were compared with those from the guaiac test for cut-off values for stool samples, positivity rates, and the receiver operating characteristic curve values. The numbers needed to screen and the numbers needed to scope to detect an advanced neoplasia (cancer, adenoma ≥10 mm, or high-grade dysplasia) were calculated. RESULTS: A positive test result was found in 1224 participants (6.2%); 1075 (87.8%) underwent a colonoscopy examination. Of these, 334 were found to have advanced neoplasia. Considering the cut-off values associated with the positivity rate of Hemoccult II (1.6%), the numbers needed to screen were 239 for Hemoccult II, 166 for a 1-sample Magstream FIT, and 129 for a 1-sample OC Sensor FIT; the numbers needed to scope were 3.3, 2.3, and 1.8, respectively. For the same false-positive rate as Hemoccult II (0.98%), the true-positive rates for Magstream and OC Sensor FITs were 0.65% and 0.90% respectively, compared with 0.42% for Hemoccult II. The OC Sensor FIT had a greater area under the receiver operating characteristic curve value than the Magstream FIT. CONCLUSIONS: Based on results from a large, population-based study, the OC Sensor FIT identifies patients with colorectal cancer with greater accuracy than the Magstream FIT. ClinicalTrials.gov number: NCT01251666.

Positivity rates and performances of immunochemical faecal occult blood tests at different cut-off levels within a colorectal cancer screening programme.

BACKGROUND: Immunochemical faecal occult blood tests have greater sensitivity for colorectal cancer screening than guaiac-based tests; however the number of positive tests required is still under discussion. METHODS: A direct comparison of Hemoccult II with two immunochemical quantitative tests (OC-Sensor and FOB-Gold) using a 2-sample strategy was performed in over 30,000 patients undergoing colorectal cancer screening in France. RESULTS: Positivity ratio between immunochemical tests and Hemoccult II varied between 2.2 (OC-Sensor) and 2.4 (FOB-Gold) for the lowest cut-off value and 1.5-1.4 for the highest cut-off value. The positive predictive value for colorectal cancer was similar for immunochemical tests and Hemoccult II, and significantly higher for immunochemical tests for advanced adenomas. The detection rate of both colorectal cancer and advanced adenomas was higher with immunochemical tests than with Hemoccult II. With the 2-sample strategy and the lowest cut-off value the detection rate of colorectal cancer almost doubled and for advanced adenomas quadrupled. CONCLUSION: For colorectal cancer screening with immunochemical faecal occult blood tests, an acceptable strategy would be 2-day sampling with at least one positive test at a cut-off between 150 and 200 ng/mL (OC-Sensor) and 176 and 234 ng/mL (FOB-Gold). Data on the ease of test interpretation and cost-effectiveness now necessary to make definitive choices.

Colorectal cancer screening: why immunochemical faecal occult blood test performs as well with either one or two samples.

BACKGROUND: Immunochemical faecal occult blood tests perform as well with either one or two samples, and better than guaiac tests with 6 samples. AIMS: Clarifying relationship between tests' performance, bleeding pattern and observation level. METHODS: The data of 32,225 average-risk subjects who performed both Hemoccult II (guaiac) and Magstream (immunochemical) tests were re-analysed by varying the cutoff and number of samples of Magstream. RESULTS: The identical performances obtained using one or two samples of Magstream (lower cutoff for one sample) at the population level were explained by opposite patterns of bleeding according to the presence of advanced neoplasias. They translated into discrepancy at the individual level: for example a 60% increase in sensitivity and 20% in specificity observed with one (39ng Hb/ml cutoff) or two samples (63ng Hb/ml cutoff) Magstream compared with Hemoccult II meant that 28.5% of the subjects testing positive with one sample (18.0% in subjects with advanced neoplasias) would have been considered negative by using two samples of Magstream at a higher cutoff (and reciprocal). CONCLUSION: The identical performance of immunochemical tests using one or two samples (different cutoff), explained by opposite pattern of bleeding according to advanced neoplasias is true only at the population level, the appropriate level for mass screening.

Analytical comparison of three quantitative immunochemical fecal occult blood tests for colorectal cancer screening.

BACKGROUND: The superiority of several immunochemical fecal occult blood tests (I-FOBT) over guaiac-based tests in colorectal cancer screening is now established. The aim of this study was to compare the analytical performance of 3 quantitative I-FOBTs. METHODS: Stool samples from 10 healthy volunteers, initially I-FOBT negative, supplemented with human blood, were used to compare reproducibility and stability of measurement at varying storage temperatures (4°C, 10°C, 20°C, and 30°C) and durations before test analysis (1 to 10 days) for 3 I-FOBTs (New Hemtube/Magstream HT, OC-Auto sampling bottle3/OC-Sensor DIANA, and FOB Gold/SENTiFOB). Concentrations ranging from 0 to 350 µg Hb/g of feces were evaluated. RESULTS: The measurement reproducibility of OC-Sensor was superior to Magstream and far superior to FOB Gold. For all tests, variability was essentially related to sampling. Detected hemoglobin (Hb) levels were substantially lower for all tests at temperatures above 20°C. At 20°C, this loss in concentration was less important with OC-Sensor (significant 1.7% daily decrease vs. 7.4% for Magstream and 7.8% for FOB Gold). At 30°C, daily loss was 8.6% with OC-Sensor, whereas after 24 hours, only 30% of the original Hb was detected with FOB Gold, compared to 70% with Magstream. No Hb was detected on day 5 for the latter 2 tests. CONCLUSIONS: About reproducibility and temperature stability, OC-Sensor performed better than Magstream and far better that FOB Gold. IMPACT: Independently of the chosen test, the delay between sampling and test processing should be reduced, the maximal admissible delay depending on ambient temperature.

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 (MG(1)), two samples were performed and at least one sample was positive (MG(2+)), both samples were positive (MG(2++)) 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 MG(1)). 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 MG(1) and MG(2+), and improved performance for MG(2m). MG(2++) 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 MG(2+) by MG(1) 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.