Physicians can minimize the heterogeneity of fecal immunochemical colorectal cancer screening tests by adjusting thresholds for positivity, according to researchers. The report is in the January issue of Gastroenterology (doi: 10.1053/j.gastro.2017.09.018).
“Rather than simply using thresholds recommended by the manufacturer, screening programs should choose thresholds based on intended levels of specificity and manageable positivity rates,” wrote PhD student Anton Gies of the German Cancer Research Center and the National Center for Tumor Diseases in Heidelberg, Germany, with his associates.
The investigators directly compared nine different fecal immunochemical assays using stool samples from 516 individuals, of whom 216 had advanced adenoma or colorectal cancer. Using thresholds recommended by manufacturers (2-17 mcg Hb/g feces) produced widely ranging sensitivities (22%-46%) and specificities (86%-98%). Using a uniform threshold of 15 mcg Hb/g feces narrowed the range of specificity (94%-98%), but sensitivities remained quite variable (16%-34%). Adjusting detection thresholds to obtain preset specificities (99%, 97%, or 93%) greatly narrowed both sensitivity (14%-18%, 21%-24%, and 30%-35%, respectively) and rates of positivity (2.8%-3.4%, 5.8%-6.1%, and 10%-11%, respectively), the researchers reported.
Increasingly, physicians are using fecal immunochemical testing to screen for colorectal neoplasia. In a prior study () investigators evaluated the diagnostic performance of six qualitative point-of-care fecal immunochemical tests among screening colonoscopy patients in Germany, and found that the tests had highly variable sensitivities and specificities for the detection of colorectal neoplasia. Not surprisingly, the most sensitive tests were the least specific, and vice versa, which is the problem with using fixed thresholds in qualitative fecal immunochemical tests, the researchers asserted.
Quantitative fecal immunochemical tests are more flexible than qualitative assays because users can adjust thresholds based on fecal hemoglobin concentrations. However, very few studies had directly compared sensitivities and specificities among quantitative fecal immunochemical tests, and “it is unclear to what extent differences ... reflect true heterogeneity in test performance or differences in study populations or varying pre-analytical conditions,” the investigators wrote. Patients in their study underwent colonoscopies in Germany between 2005 and 2010, and fecal samples were stored at –80 °C until analysis. The researchers calculated test sensitivities and specificities by using colonoscopy and histology reports evaluated by blinded, trained research assistants.
“Apparent heterogeneity in diagnostic performance of quantitative fecal immunochemical tests can be overcome to a large extent by adjusting thresholds to yield defined levels of specificity or positivity rates,” the investigators concluded. Only 16 patients in this study had colorectal cancer, which made it difficult to pinpoint test sensitivity for this finding, they noted. However, they found similar sensitivity estimates for colorectal cancer in an ancillary clinical study.
Manufacturers provided test kits free of charge. There were no external funding sources, and the researchers reported having no conflicts of interest.