Immunochemical FOBT Confirms Positive Guaiac FOBT

February 1, 2006

Practice standards call for colonoscopy for all patients who have positive guaiac fecal occult blood test (FOBT) screening for colorectal cancer. A new study suggests that using a confirmatory immunochemical FOBT in patients who are only weakly or moderately positive on guaiac FOBT would eliminate many false positives and reduce the need for colonoscopy without jeopardizing outcomes.

DUNDEE, Scotland-Practice standards call for colonoscopy for all patients who have positive guaiac fecal occult blood test (FOBT) screening for colorectal cancer. A new study suggests that using a confirmatory immunochemical FOBT in patients who are only weakly or moderately positive on guaiac FOBT would eliminate many false positives and reduce the need for colonoscopy without jeopardizing outcomes.

Callum G. Fraser, PhD, and his colleagues estimate that this two-tiered approach might reduce the need for colon-oscopy by about 30%, with major implications for costs, patient inconvenience, and colonoscopy-associated morbidity (The Lancet Oncology, published online January 6, 2006. DOI:10.1016/S1470-2045(05)70473-3).

The study subjects (age 50 to 69) were participating in a pilot study to assess the feasibility of a national colorectal screening program based on non-dietary-restricted guaiac FOBT testing. In this study, participants with a strongly positive guaiac FOBT (five or six positive ovals) were offered colonoscopy without further testing. Those with a weakly positive test (one to four positive ovals) were asked to do a second test, and if any oval was positive, colonoscopy was offered. If all six ovals were negative, a third guaiac FOBT was requested. If any oval was positive on the third test, colonoscopy was offered.

In the current study, patients with positive guaiac FOBT results indicating a need for colonoscopy were offered immunochemical FOBT before the procedure. Two samples were taken for immunochemical FOBT testing; these were scored as both negative (N/N); one negative, one positive (N/P); or both positive (P/P). A total of 801 patients returned all required samples, and 795 of these had colonoscopy.

Study Results

The extent of guaiac FOBT positivity correlated significantly with immunochemical FOBT positivity, Dr. Fraser reported, and positive immunochemical FOBT testing correlated with a finding of colorectal cancer on colonoscopy. The results showed that 38 (8%) of 497 patients who were P/P on immunochemical FOBT had colorectal cancer, compared with only 1 (less than 1%) of 171 N/N subjects and 1 (less than 1%) of 127 N/P participants (odds ratio 7.57). Sensitivity and specificity of immunochemical FOBT for cancer were 95% and 39.5%, respectively. In addition, subjects with P/P immunochemical FOBT were more likely to have large adenomatous polyps (larger than 10 mm diameter) or multiple adenomatous polyps (more than three) than those who were N/N or N/P (odds ratio 3.11).

"We have shown a positive relation between strength of positivity on guaiac FOBT and the results of immunochemical FOBT," Dr. Fraser said. "Our findings suggest that the small number of individuals who are strongly positive [defined as 5 or 6 positive ovals] on first guaiac FOBT should not have immunochemical FOBT and should proceed directly to colonoscopy, thus improving screening efficiency."

Further, he said, "we recorded an association between findings of immunochemical FOBT and the presence or absence of neoplastic disease. Negative immunochemical FOBT (N/N or N/P) was associated with a less than 1% chance of invasive cancer, which approximates with the population prevalence in the age group studied and the level of cancer detection expected if colonoscopy was used as the primary screening modality."

Thus, he said, in a two-tiered screening approach, individuals who are guaiac FOBT positive but negative on at least one immunochemical FOBT could be excluded from colonoscopy without compromising the screening goal of identifying subjects who are at high risk of colorectal cancer. However, he said, with the two-tiered approach, individuals with a weakly positive guaiac FOBT (one to four positive ovals) and a positive immunochemical FOBT test would be offered colonoscopy.

Although immunochemical FOBT is more expensive than guaiac FOBT, use of this strategy for those who are weakly positive on initial guaiac FOBT would decrease the need for colonoscopy. Dr. Fraser suggests that such subjects be offered retesting after 2 years.

"I do not know what the exact cost savings would be at this stage, but I do know that the cost of the immunochemical test [£4.50 UK] is far cheaper than a colonoscopy," Dr. Fraser told ONI. "In Scotland, we eventually plan to offer colorectal cancer screening to everyone between age 50 and 74 every 2 years. This means that when we roll out the program, we will be inviting 680,000 people per year for testing. If we can cut down on unnecessary colonoscopy, this would make the program more cost-effective."

Dr. Fraser is in the Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee. Study coauthors are Professors Francis A. Carey and Robert J. C. Steele from Dundee; Catriona Matthew, MSc, Scottish Bowel Screening Centre, Kings Cross, Dundee; Professor N. Ashley G. Mowat, Aberdeen Royal Infirmary, Foresterhill, Aberdeen; and Dr. John A. Wilson, Victoria Hospital, Kirkcaldy, Fife.