Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. Regular screening is critical for timely diagnosis and treatment. Screening is routinely done using endoscopy and fecal occult blood tests (FOBT), that can measure minute traces of blood in stool samples, otherwise invisible to the naked eye. Given the non-invasive, easy-to-use and simple nature of FOBTs along with significantly lower costs, they are now being widely used for screening of populations at risk of CRC.

One such newly developed method is the fecal immunochemical test (FIT) that can detect the blood protein, hemoglobin (Hb), in stool samples, and is now being employed for large scale population screening. While self-administered, qualitative FITs are interpreted either as positive or negative, laboratory-based quantitative FITs reflect a continuous range of values. The detection range and positivity threshold for these tests, however, differs across kits from different manufacturers.

Testing for Quality

Researchers from China have now gone a step further in testing the accuracy and performance of qualitative and quantitative FITs by comparing these tests head-to-head at preset and adjusted cut-off values, in their new study. Explaining the clinical significance of their study, Prof. Min Dai, who led the study states, “In China, qualitative FITs have been widely used for colorectal cancer (CRC) screening, because of their low cost, ease of use, and visual interpretation. As population-based studies on the diagnostic performance of qualitative FITs are sparse, their application and generalization are always dubious, underscoring the need for comparative assessments.” 

Their paper was published in Volume 134 Issue 11 of the Chinese Medical Journal.

Their current analysis is based on stool samples collected from participants of their previous randomized controlled trial known as TARGET-C, which assessed the strategies of CRC screening. Participants eligible for endoscopy from this trial, were instructed to collect their stool sample prior to the scheduled procedure; 3,144 of these samples including 0.8% CRCs (aggressive), 7.3% advanced adenomas (moderate severity), 19.8% non-advanced adenomas (mild severity), and 72.1% participants without significant findings at colonoscopy, were then processed and used for evaluation of three self-administered qualitative FITs, and one lab-based quantitative FIT, in the current study.

Each qualitative FIT kit had a specified pre-set detection threshold of 8.0 (FIT1), 14.4 (FIT2), and 20.8 (FIT3) µg Hb/g, while the threshold for the quantitative test was set at 20.0 µg Hb/g. The researchers found a decrease in the positivity rate from 12.1% to 4.5% as the threshold increased from 8.0 µg Hb/g to 20.8 µg Hb/g. Moreover, the positivity rate was higher for the all the three qualitative tests compared to the quantitative FIT.

Next, they went on to evaluate the accuracy of the tests in determining various disease stages. While, the qualitative tests had high detection sensitivities, they had decreased specificity in differentiating between the different disease stages, compared to the quantitative test.

Interestingly, the researchers noted that this heterogeneity in the sensitivity for detecting advanced neoplasm, including CRC as well as advanced adenoma, between qualitative and quantitative FITs was nullified as the threshold of the quantitative test was adjusted to a positivity rate or specificity comparable to that of the qualitative tests, respectively. Also, the detection sensitivities of the tests did not vary significantly with other variables such as sex, body mass index, medical history, and lifestyle factors such as smoking, thus making them a robust detection strategy for CRC screening.

Overall, these findings suggest that consistency or disparities in the sensitivity and other indicators concerning diagnostic accuracy of FITs largely depends on the positivity threshold; both qualitative and quantitative tests are therefore reliable in the diagnosis of CRC. Nevertheless, given similar test performance but different application characteristics, appropriate types of FITs should be selected by the health providers to meet specific demands in the actual screening setting.

Highlighting the long-term implications of their work, Prof. Dai concludes, “Given the large population basis of China, it is of great public health significance to select an appropriate type of FIT in CRC screening. Our findings suggest that the widespread use of qualitative FITs in China could achieve equivalent diagnostic performance to the quantitative tests when thresholds are adjusted to comparable levels of specificity or positivity rate.”

Featured Image: Study compares the diagnostic performance of self-administered qualitative and laboratory based quantitative fecal tests for colorectal cancer screening. Illustration: Chinese Medical Journal