Fecal occult blood versus DNA testing: indirect comparison in a colorectal cancer screening population

Abstract

BackgroundA multitarget stool DNA test (MSDT) that showed higher sensitivity but lower specificity than a fecal immunochemical test (FIT) for hemoglobin in one recent study from the US and Canada, is increasingly used for colorectal cancer (CRC) screening, despite its ~20-fold higher costs compared to FITs. We aimed to assess diagnostic performance of a quantitative FIT in an independent study among participants of screening colonoscopy and to compare it with the previously reported performance of MSDT.MethodsA total of 3494 participants, aged 50–84 years, who underwent screening colonoscopy in private gastroenterological practices in Germany, and who provided a stool sample before colonoscopy to be evaluated by a commercially available quantitative FIT (FOB Gold®) were included. Diagnostic performance (sensitivity, specificity) for detecting CRC or advanced precancerous lesions (APCLs) was evaluated by comparison of test results with findings at screening colonoscopy. In addition to the original cutoff, we used an adjusted cutoff yielding the same specificity as reported for the MSDT to enhance comparability.ResultsThe most advanced finding at colonoscopy was CRC and APCL in 30 (0.86%) and 359 (10.3%) cases, respectively. At a cutoff yielding the same specificity as reported for MSDT (86.6%), the sensitivities (95% CI) of the FIT for detecting CRC and APCL >1 cm were 96.7% (82.8–99.9%) and 54.3% (48.3–60.3%), respectively. These sensitivities are higher than those reported for MSDT (92.3% and 43.6%, p=0.66 and 0.003, respectively).ConclusionIn this large screening population, FIT showed equivalent or better diagnostic performance in comparison to reported performance of MSDT.

Comment on “Fecal occult blood versus DNA testing: indirect comparison in a colorectal cancer screening population”

“…Nevertheless, in order to address any potential impact of the differences in age structure we reported results of additional analyses in which we adjusted our findings to the age structure of the MSDT study. As reported in our article, 1 this age adjustment did not alter any of our conclusions. Selective reporting of results favoring MSDT: in his letter, Dr. Ahlquist selectively reports a single statistic from the MSDT study that apparently favors the author’s view, while not addressing other, less favorable statistics, such as the 20-fold higher rate of non-evaluable results of MSDT compared to FIT.…”

“…Although all of the specific concerns raised by Dr. Ahlquist were carefully and critically addressed in our article, 1 we would like to briefly add the following few comments to each of his concerns: Major differences across study populations: it is correct that the MSDT study by Dr. Ahlquist, as a result of intentional oversampling of adults ≥65 years of age, had included a much larger proportion (63%) of adults ≥65 years of age than our study (33%). Due to intentional oversampling of adults ≥65 years of age, the MSDT study was not representative of a true screening population.…”

“…We appreciate Dr. Ahlquist’s interest in our article 1 that challenges his previously disseminated claim that the multitarget stool DNA test (MSDT) represents “the new high bar benchmark for noninvasive CRC screening”. 2 Expectations on the diagnostic performance of this test should in fact be high, given the following facts not mentioned by Dr. Ahlquist: The costs of MSDT exceed the costs of fecal immunochemical test (FIT) for hemoglobin, the noninvasive test of choice in an increasing number of countries, 3 ~20-fold.…”

“…A multi-target stool DNA test (MT-sDNA) has emerged as a new approach to colorectal cancer (CRC) screening, and in the US, it is approved by federal regulatory bodies, endorsed in societal screening guidelines, and covered by government and private insurers. In their recent paper, 1 Brenner and Chen concluded that CRC screening sensitivity by fecal immunochemical test (FIT) for occult blood is equal to or better than that of MT-sDNA when tests are compared at matched specificity. However, concerns can be raised regarding their methodology and data.…”

“… Major differences exist across study populations: a cardinal scientific principle dictates that tests are best compared directly within the same population. In this study from Germany, 1 observed FIT results were compared with reported MT-sDNA results from a large multicenter US study. 2 Their indirect comparison is confounded by between-population differences in patient, lesion, and other variables.…”