Table 3. Randomized Controlled Screening Trials: Fecal Occult Blood Testing continued...
In one study, 2,188 patients scheduled for colonoscopy because of an elevated risk due to personal or family history of colorectal neoplasm, positive gFOBT result, change in bowel habits, anemia, abdominal pain with weight loss, or anal symptoms were invited to participate in a comparative assessment of iFOBT against colonoscopy findings. After exclusions for health and cognitive reasons, 1,859 patients were offered iFOBT, 1,116 patients adhered to the protocol, and 1,000 patients completed the procedure. Sensitivity and specificity were calculated at various cut-points. At a cut-point of 100 ng/mL, sensitivity and specificity were, respectively, 88.2% and 89.7% for cancer and 61.5% and 91.4% for any clinically significant neoplasia (cancer and advanced polyps). At 150 ng/mL the respective sensitivities and specificities were 82.4% and 91.9% for cancer and 53.8% and 95% for any clinically significant neoplasia. Calculations were based on the most severe pathologic finding from colonoscopy and the highest fecal-hemoglobin concentration measured by iFOBT applied to three stool samples collected prior to the colonoscopy. Stool samples were collected by patients following iFOBT kit instructions and analyzed by the OC-MICRO analyzer (from the Eiken Chemical Company in Tokyo, Japan).
In another study, 21,805 asymptomatic patients received iFOBT based on one stool sample collected by patients following the kit instructions on the day of or the day before the colonoscopy. Stool samples were analyzed using the Magstream 1,000/Hem SP automated system (from Fujirebio Incorporated, Tokyo, Japan), which is based on the HemeSelect system (from Beckman Coulter, Palo Alto, California). Sensitivity and specificity based on subsequent colonoscopy were, respectively, 65.8% and 94.6% for cancer and 27.1% and 95.1% for advanced neoplasm.
Fecal immunochemical tests may vary with regard to numbers of stools tested and cut-off values for a positive result.[29,32,33]
A systematic review to evaluate the comparative diagnostic performance of gFOBT and iFOBT in the context of a decision to introduce screening for CRC in the United Kingdom, included 33 studies evaluating gFOBT and 35 studies evaluating iFOBT, including nine that evaluated both gFOBT and iFOBT. There was no clear evidence for superiority of either gFOBT or iFOBT. Sensitivities for the detection of all neoplasms ranged from 6.2% (specificity 98%) to 83.3% (specificity 98.4%) for gFOBTs and 5.4% (specificity 98.5%) to 62.6% (specificity 94.3%) for iFOBT. Increasing sensitivity entailed adjusting cut-points to decrease specificity. Sensitivities were higher for the detection of CRC and lower for adenomas.
Some studies have utilized the quantitative ability of iFOBT to consider detection and specificity at various test cut-points for defining a positive test. One study  found that reducing the cut-point from the standard 100 ng/mL to 50 ng/mL increased the detection of advanced adenomas but had little impact on the detection of cancer. The number of colonoscopies required to detect a single advanced adenoma or cancer increased from 1.9 to 2.3; a 20% increase. Specificity declined from 97.8% to 96%.