Mathematical models have been constructed to extrapolate the results of screening trials to screening programs for the general population in community health care delivery settings. These models project a reduction in CRC mortality or an increase in life expectancy using currently available screening methodology.[17,18,19,20] The anticipated success of such methodology is critically dependent on the appropriate use of the FOBT and an effective clinical management plan.[21,22]
A systematic review done through the Cochrane Collaboration examined all CRC screening randomized trials that involved gFOBT testing on more than one occasion. The combined results showed that trial participants allocated to screening had a 16% lower CRC mortality (RR = 0.84; 95% CI, 0.78-0.90). There was, however, no difference in all-cause mortality between the screened and control groups (RR = 1.00; 95% CI, 0.99-1.02). Furthermore, the trials reported a low positive predictive value (PPV) for the FOBT test, suggesting that most positive tests were false positives. From the trials with nonrehydrated slides (Funen and Nottingham), the PPV was 5.0% to 18.7%, while the PPV in the trials using rehydrated slides (Goteborg and Minnesota) was 0.9% to 6.1%. The report contains no discussion on contamination in the control arms of the trials and no information on treatment by stage.[23,24]
On initial (prevalence) examinations, from 1% to 5% of unselected persons tested with gFOBT have positive test results. Of those persons with positive test results, approximately 2% to 10% have cancer and approximately 20% to 30% have adenomas,[25,26] depending on how the test is done. Data from randomized controlled trials (RCT) are summarized in Table 3.
Table 3. Randomized Controlled Screening Trials: Fecal Occult Blood Testing
N/A = not available.
a % Localized = T1-3 N0 M0.
|Site||Population Size ||Positivity Rate (%) ||% Localizeda||Testing Interval||Relative Mortality Reduction|
|Minnesota [5,6]||48,000 ||Unrehydrated: 2.4% || 59 || 53 ||Annual || 33%|
|�|| Rehydrated: 9.8% ||�||�|| Biennial || 21%|
|United Kingdom || 150,000 || Unrehydrated: 2.1% ||52||44 ||Biennial || 15%|
|Denmark ||62,000 ||Unrehydrated: 1.0% ||56|| 48 ||Biennial ||18%|
|Sweden ||27,000 ||Unrehydrated: 1.9%||65||33||�||N/A|
|�||Rehydrated: 5.8% ||�||�||�||�|
Newer FOBTs: Nonrandomized Controlled Trial Evidence
Newer FOBTs have been developed to specifically detect human hemoglobin (immunochemical FOBT, abbreviated iFOBT in the literature) in contrast to traditional guaiac-based hemoglobin FOBT, which are not specific to human hemoglobin and detect peroxidase-like activity. IFOBT has not been evaluated in a RCT but has been investigated in clinical studies.
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).