A variety of fecal immunochemical tests for hemoglobin are used in colorectal cancer screening.
It is unclear to what extent differences in reported sensitivities and specificities reflect true heterogeneity in test performance or differences in study populations or varying pre-analytical conditions.
Dr Hermann Brenner and the research team from Germany, directly compared the sensitivity and specificity values with which 9 quantitative fecal immunochemical tests detected advanced neoplasms in a single colorectal cancer screening study.
Pre-colonoscopy stool samples were obtained from participants of screening colonoscopy in Germany from 2005 through 2010 and frozen at –80°C until analysis.
The stool samples were thawed, homogenized, and used for 9 different quantitative fecal immunochemical tests in parallel.
|Adjusting thresholds to yield a specificity of 99% resulted in almost equal positivity rates|
Colonoscopy and histology reports were collected from all participants and evaluated by 2 independent, trained research assistants who were blinded to the test results.
Comparative evaluations of diagnostic performance for advanced neoplasm were made at preset manufacturers′ thresholds at a uniform threshold and at adjusted thresholds yielding defined levels of specificity.
Of the 1667 participants who fulfilled the inclusion criteria, the team noted that all cases with advanced neoplasm and 300 randomly selected individuals without advanced neoplasm were included in the analysis.
Sensitivities and specificities for advanced neoplasm varied widely when the doctors used the preset thresholds or the uniform threshold.
The researchers observed that adjusting thresholds to yield a specificity of 99%, 97%, or 93% resulted in almost equal sensitivities for detection of advanced neoplasm and almost equal positivity rates.
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.
Dr Brenner's team commented that: "Rather than simply using thresholds recommended by the manufacturer, screening programs should choose thresholds based on intended levels of specificity and manageable positivity rates".