A single dose of oral aspirin two days prior to fecal immunochemical testing (FIT) did not significantly affect detection of advanced neoplasms compared with placebo, according to a randomized trial including more than 2,000 German patients ages 40 to 80 years. The study found that at a cutoff of 10.2-μg Hb/g stool, FIT sensitivity was 40.2% with aspirin and 30.4% with placebo and, with a cutoff of 17-μg Hb/g stool, sensitivities were 28.6% and 22.5%, respectively.
The trial by Brenner and colleagues concluded that aspirin taken 2 days before FIT testing did not increase test sensitivity. But does the trial rule out an increase in sensitivity? Although the results did not reach the conventional, albeit controversial, level of statistical significance (P < 0.05), the confidence intervals are wide and most are on the side of increased sensitivity. The study, for all its methodologic strengths, did not have enough statistical power to exclude a clinically important increase in sensitivity (e.g., 22.2%).
Specificity is not emphasized in the article although it is also important when choosing a screening test because all positive test results, including false positives, would be followed with colonoscopy. In the trial, the false-positive rate is almost twice as high after receipt of aspirin, and the corresponding decrease in specificity is statistically significant. We see the usual trade-off between sensitivity and specificity, typically in relation to changing the threshold for an abnormal test result. In this case, false positives probably occur because aspirin increases the amount of blood in stool, pushing it closer to the test's threshold for abnormal in persons both with and without advanced neoplasms.
Can these results be generalized to other settings? A problem for studies of FIT is the number of different versions of the test. By recent count, there are 65 tests, 26 of which are available in the USA. Few have been rigorously studied, so the evidence for comparative effectiveness is weak. Generalizing from this study to other FIT tests depends on the assumption that they all have similar sensitivities and specificities, which is implausible because they use different laboratory methods and cutpoints. Even the 3 tests in this study, which used 2 cutpoints for the quantitative test and the qualitative test, performed differently.
Because FIT is widely used for screening throughout the world, improved performance would be welcome. The results of the study by Brenner and colleagues do not support routinely recommending aspirin before FIT for colorectal cancer screening. Perhaps a focus on improving FIT screening rates—which tend to decline year to year in individual patients and could be improved in most settings—would better serve efforts to prevent colorectal cancer deaths.