In patients who performed the two tests, the I‐FOBT had a higher sensitivity for both cancer and high risk adenomas irrespective of the cut‐off value used for I‐FOBT. With the usual cut‐off point (20 ng haemoglobin/ml), this gain in sensitivity was associated with a decrease in specificity, 2.17 extra false positives being associated with the detection of one extra advanced neoplasia (cancer or high risk adenoma). Using a higher cut‐off point, our results suggest that the I‐FOBT rather than the G‐FOBT offers a gain in both sensitivity and specificity. When I‐FOBT was used at a cut‐off value associated with a positivity rate similar to G‐FOBT, it offered a gain in sensitivity of 90% and a decrease in false positive rate of 33% for advanced neoplasia.
The study had several drawbacks. To estimate screening test performances for cancers and high risk adenomas, the ideal is to obtain the disease status for all individuals, independent of the screening test results. With the exception of the recent study by Morikawa et al
large scale asymptomatic populations have not undergone screening, and available direct estimation of I‐FOBT performance originates mainly from high risk individuals referred for colonoscopy.10,14
Hence the results may not be directly applicable to the general average risk population. Studies conducted in large samples of the general population, with follow‐up for individuals with negative tests, provided complete and reliable information on cancer but not on high risk adenomas.15,16,17
Our study was conducted in an average risk population but our analysis was conducted before the collection of cancers by local registries, and does not therefore provide an estimation of the sensitivity and specificity of each test. However, it does enable direct comparison of the sensitivity and specificity of the two tests by calculating proper ratios (RSN and RFP), as suggested by Schatzkin et al
and Cheng et al
and thus quantification of the potential gain obtained by the substitution of G‐FOBT by I‐FOBT. This method allowed the calculation of the 95% confidence interval for each ratio; the 95% confidence interval for RSN for detection of invasive colorectal cancer was probably underestimated in our study because of the small number of cases.
A significant proportion (20%) of individuals with a positive screening test did not undergo colonoscopy. This proportion was no higher than those usually observed in mass screening campaigns in France. However, it produced potential bias as the risk of cancer has been suggested in a previous French study17
to be higher for people refusing a colonoscopy after a positive test. In our case, as the proportion of people not having colonoscopy after a positive test did not differ with regard to whether one or both screening tests were positive, it did not produce bias in the comparison between the tests.
Despite extensive studies, including several randomised studies, there is still no consensus on the best strategy for colorectal cancer screening for average risk populations, and guidelines vary from one country to another and from one society to another. Nevertheless, FOBT is included in all recent guidelines and reviews.19,20
Limitations of the guaiac tests, in particular their low sensitivity, encourage researchers to search extensively for alternative FOBT techniques. An increasing number of recent papers highlighted their interest in the use of immunochemical tests. Our study is in agreement with these studies, conducted in general or high risk populations, emphasising the high sensitivity of I‐FOBT for cancer and adenomas,9,10,21,22
and its superiority over G‐FOBT.14,15,16,23
The development of automated systems has increased the reliability and decreased the cost of test processing and reading. The technology evaluated in our study, Magstream 1000/Hem SP (Fujirebio), has previously been studied in individuals referred for colonoscopy,10
and in two population based studies.9,24
The recent study by Morikawa et al
comparing this I‐FOBT technology with colonoscopy in 21
805 Japanese asymptomatic individuals provided reliable and promising results.9
However, using the usual threshold of 20 ng haemoglobin/ml, and although the study population was younger than those usually screened (mean age 48.2 years), the proportion of patients with a positive test was relatively high (5.6%). Such a high positivity rate, which would be even higher in older populations, could be inappropriate in biennial strategies. As suggested in previous studies,17,25
by increasing the positivity threshold of quantitative I‐FOBT, an appropriate positivity rate can be obtained while maintaining a substantial gain in sensitivity. The ideal balance between sensitivity and specificity/positivity rate depends on health care organisation and cost, and is likely to vary between countries. Our study, conducted in a 50–74 year average risk population, showed that with a positivity rate of 2.4%, identical to the Hemoccult test, I‐FOBT increased the number of true positives (cancers and high risk adenomas) by nearly 2 (1.9) and decreased the number of false positive results by 1.5.
Evidence in favour of the use of the I‐FOBT over the G‐FOBT is increasing. I‐FOBT tests have no dietary or medication restrictions. These tests have superior sensitivity and specificity, the gain being more important for high risk adenomas than for cancers. They also have a higher compliance rate23,26,27
and the automated reading technology allows the choice of the ideal positivity rate. As suggested in recent reviews,5,7
it is time to give colorectal cancer screening a new future by using I‐FOBT instead of G‐FOBT.