Surveillance colonoscopy is the standard recommended strategy in the United States after polyp removal during colonoscopy. The recommended surveillance interval depends on the size, number, and type of polyps found. However, the US Multi-Society Task Force acknowledged that evidence showing polypectomy actually reduces colorectal cancer incidence or death is limited, particularly for patients with lower-risk findings.
In contrast, guidelines from Canada, the United Kingdom, and Europe recommend fecal immunochemical testing (FIT) instead of colonoscopy after removal of low-risk adenomas. These international guidelines cite low to moderate quality evidence supporting stool testing as a sufficient surveillance approach for lower-risk patients.
This divergence in recommendations reflects a genuine uncertainty about the optimal surveillance strategy. Colonoscopy carries procedural risks, patient inconvenience, and substantial cost (estimated median total cost of approximately $1,800), while FIT is a simple home test with an estimated median cost of approximately $20. Understanding FIT performance in postpolypectomy patients is therefore of great clinical and public health importance.
Fecal immunochemical testing (FIT) is a non-invasive screening method that detects hemoglobin in stool samples. Because colorectal tumors and advanced precancerous lesions bleed more than normal tissue, elevated fecal hemoglobin can signal the presence of significant disease.
Most US FIT tests provide a qualitative positive or negative result using a standard cutoff of 100 nanograms of hemoglobin per milliliter (ng/mL) of buffer. Quantitative FIT devices can report an exact numerical hemoglobin level, enabling researchers and clinicians to explore whether different thresholds might improve test performance.
Advanced colorectal neoplasia (ACN) is the main target of surveillance and includes advanced precancerous lesions (APL) such as large adenomas, villous or tubulovillous adenomas, serrated lesions, and adenomas with high-grade dysplasia, as well as carcinoma in situ and invasive adenocarcinoma. Detecting ACN early enables timely treatment before cancer develops or progresses.
This study is a secondary exploratory analysis of data from the BestFIT study, a prospective, double-blinded, multicenter trial conducted between 2017 and 2022 that compared five different FIT tests using colonoscopy and pathology as the reference standard. The analysis was restricted to Iowa participants who had undergone surveillance (rather than screening) colonoscopy and for whom previous colonoscopy data were available.
In total, 449 participants were included. Their mean age was 65.4 years, 53.2% were women, and 92.7% were White, reflecting a largely older, well-educated, and socioeconomically advantaged population. All participants completed a quantitative OC-Auto FIT test before starting their colonoscopy preparation, with a median interval of 11 days between stool test and colonoscopy.
Patients were classified by their most recent previous colonoscopy findings into three groups: low risk (no more than 2 small polyps under 1 cm), intermediate risk (more than 2 but fewer than 10 small polyps), and high risk (advanced precancerous lesion on the previous exam). Of the 449 patients, 313 were low risk, 65 were intermediate risk, and 71 were high risk based on prior colonoscopy findings.
The primary statistical goal was to identify an optimal FIT hemoglobin cutoff for detecting ACN in surveillance patients. The researchers used the Youden Index, defined as the threshold that maximizes the combined value of sensitivity plus specificity minus 100. Geometrically, this corresponds to the point on the receiver operating characteristic (ROC) curve that is farthest above the diagonal chance line.
Diagnostic accuracy was reported as sensitivity and specificity with 95% confidence intervals calculated using exact binomial methods. The standard 100 ng/mL threshold and the derived optimal threshold were compared using the McNemar test for paired proportions. Positive and negative predictive values were also calculated for both cutoffs.
Because surveillance programs involve repeated testing over years, the researchers also estimated cumulative sensitivity and specificity across 3 rounds of FIT testing. The cumulative sensitivity formula accounts for the probability that at least one round out of multiple tests would detect an ACN, assuming independent testing and no disease progression. Estimates were calculated for both 100% and 50% adherence with repeat testing in years 2 and 3.
The median interval between the most recent previous colonoscopy and the surveillance procedure was 5.0 years. Colonoscopy quality was high: 89.3% of procedures had adequate or better bowel preparation, and the cecum was reached in 98.4% of cases with no procedural complications.
Advanced colorectal neoplasia was detected in 55 participants (12.3%), all of which were advanced precancerous lesions. No invasive cancers were identified. Among the 71 patients who had an advanced precancerous lesion on their previous colonoscopy, 18.3% had ACN at surveillance, compared with 11.1% of those without prior advanced findings, though this difference was not statistically significant (p = 0.09).
Median FIT hemoglobin levels varied by risk group: 2.0 ng/mL in low-risk patients, 7.0 ng/mL in intermediate-risk patients, and 1.0 ng/mL in high-risk patients. These low median values illustrate why the standard 100 ng/mL cutoff misses most ACN cases in this population.
For patients with previous low-risk or intermediate-risk findings, the Youden Index identified 26 ng/mL as the optimal hemoglobin threshold. This is nearly four times lower than the standard FDA-approved cutoff of 100 ng/mL.
At the standard 100 ng/mL cutoff, sensitivity for ACN was only 14.3%, meaning 85.7% of advanced precancerous lesions went undetected. Lowering the threshold to 26 ng/mL significantly increased sensitivity to 35.7% (p = 0.003). However, specificity decreased significantly from 95.5% to 79.2% (p less than 0.001), meaning more patients without ACN would receive a positive test result and be referred for confirmatory colonoscopy.
The negative predictive value remained high and similar at both cutoffs (89.9% vs. 90.8%), meaning a negative test was reassuring at either threshold. The area under the ROC curve was only 0.57, indicating that single-round FIT testing had limited discriminant ability regardless of the cutoff chosen. For patients with a prior advanced precancerous lesion, the 100 ng/mL cutoff yielded only 15.4% sensitivity, suggesting FIT is not appropriate as a surveillance strategy for high-risk patients.
Single-round FIT testing has limited sensitivity, but performing FIT annually over multiple years substantially increases the cumulative probability of detecting an ACN if one is present. Using the standard 100 ng/mL cutoff, estimated cumulative sensitivity across 3 rounds of testing was 37.1% with 100% adherence and 26.0% with only 50% adherence in years 2 and 3.
With the optimal 26 ng/mL cutoff, estimated cumulative sensitivity jumped to 73.4% at 100% adherence and 56.6% at 50% adherence over 3 rounds. These estimates assume independent detection with each test and no disease progression between rounds.
The tradeoff is a marked reduction in cumulative specificity. With the lower cutoff and 100% adherence over 3 rounds, cumulative specificity falls to 49.7%, meaning many patients would receive at least one positive result over 3 years and require diagnostic colonoscopy. However, given that the underlying risk of colorectal cancer in low-risk adenoma patients is very low (estimated 4.5 cases per 10,000 person-years), the authors suggest that even imperfect serial FIT testing may represent a reasonable surveillance alternative.
These findings suggest that quantitative FIT surveillance calibrated to a lower hemoglobin threshold could serve as a less invasive, less expensive alternative to colonoscopy for patients whose previous colonoscopy found only low-risk or intermediate-risk polyps. Given the very low cancer incidence in this group, the primary goal of surveillance is detecting advanced precancerous lesions before they progress.
The ongoing COOP trial (Colonoscopy vs. Stool Testing in Older Patients with Colon Polyps), funded by the Patient-Centered Outcomes Research Institute and enrolling nearly 9,000 adults aged 65 to 82, will provide more definitive evidence. This randomized trial compares annual qualitative FIT versus a one-time colonoscopy in patients with 2 or fewer non-advanced polyps on the most recent exam, with completion expected in 2029.
Important limitations of the current study include its single-center setting with a largely White and well-educated population, the small sample size which prevented estimation of separate optimal cutoffs for each risk subgroup, and the absence of quantitative FIT values in routine US clinical practice. The researchers also note that individual FIT tests vary in diagnostic performance and that clinicians must weigh the reduced specificity of serial testing against the potential benefit of avoiding colonoscopy. Nonetheless, the cost, convenience, and patient acceptance advantages of FIT testing make further evaluation worthwhile.