Divergent detection rates of fecal immunochemical test and questionnaire-based risk assessment for detecting proximal and distal advanced colorectal adenomas
Colorectal cancer (CRC) is the third most common cancer globally, but early detection of precancerous adenomas can cut deaths by up to 60%. Two of the most widely used CRC screening tools—fecal immunochemical tests (FITs) and questionnaire-based risk assessments (QRAs)—are designed to spot these growths early. But new research from China suggests they work differently for adenomas in the upper (proximal) vs. lower (distal) parts of the colon, with FITs much better at finding distal advanced adenomas than proximal ones.
A team of researchers from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing analyzed data from the TARGET-C trial—a large, population-based CRC screening study—to compare how FITs and QRAs perform across colon regions. The study included 3,825 adults aged 40–74 who underwent colonoscopy: 1,665 for routine screening, 1,436 after a positive FIT, and 724 after a positive QRA.
What Are FITs and QRAs?
FITs are simple, at-home tests that detect human hemoglobin (blood) in stool, a sign of colonic growths. They’re used in screening programs worldwide because they’re noninvasive and easy to use. QRAs, on the other hand, use questions about CRC risk factors (like age, sex, family history, smoking, and body mass index) to identify people who need further testing (like colonoscopy).
Previous research had hinted that FITs are more sensitive for distal (lower colon/rectum) adenomas, while risk factors like smoking and BMI might affect proximal (upper colon) cancer more. But until now, no study had directly compared how FITs and QRAs perform for adenomas in different colon regions in a real-world screening setting.
How the Study Worked
The researchers used a modified Asian-Pacific Colorectal Screening (APCS) score for QRA: participants scored points for being male, older, having a family history of CRC, smoking, or a BMI ≥23. A score of 4 or higher meant high risk and a colonoscopy referral. For FITs, they used a qualitative test (Pupu Tube) that turns positive if stool hemoglobin exceeds 4 mg/g—lower than many other screening programs.
Advanced adenomas (the most precancerous type) were defined as growths ≥1 cm wide, with high-grade dysplasia, or villous/tubular-villous tissue. The proximal colon included the splenic flexure (a bend in the colon) and all segments above it; the rest was considered distal. If someone had multiple adenomas, the most advanced one determined their outcome.
Key Findings
The study’s baseline—screening colonoscopy—found advanced adenomas in 3.12% of distal colon/rectum cases and 2.52% of proximal cases (a “rate ratio” of 1.24, meaning distal was slightly more common). But when looking at people who had colonoscopy after a positive FIT, the distal detection rate jumped to 8.64%—more than twice the proximal rate of 3.90% (rate ratio: 2.21). This difference was statistically significant, meaning it wasn’t due to chance.
For QRAs, the gap was smaller: 6.91% distal vs. 4.70% proximal (rate ratio: 1.47), but this wasn’t statistically significant. The researchers noted that QRA’s risk factors (like smoking and BMI) might have different impacts on proximal vs. distal adenomas—a finding supported by earlier studies.
Why the Difference?
FITs rely on detecting blood, so distal adenomas (which are often “pedunculated” or stalk-like) are more likely to bleed than flat, “sessile” proximal adenomas. Plus, stool takes longer to move through the proximal colon, so hemoglobin breaks down more, making it harder for FITs to detect. Even with a lower FIT threshold (4 mg/g), the study found no improvement in proximal detection—a surprise, since some experts thought lower thresholds might help.
For QRAs, the non-significant difference might come from how risk factors affect different colon regions. For example, smoking is more strongly linked to distal CRC, while obesity might impact proximal CRC more. The QRA used in this study includes both factors, which could balance out the detection rates—but more research is needed to confirm.
Limitations and Next Steps
The study has a few caveats: it’s based on a single round of screening (multiple rounds might widen the gap) and the number of advanced adenomas was small, leading to wide confidence intervals. The researchers also noted that QRA participants had different risk profiles (older, more male, higher BMI) because those factors are part of the risk score—something to consider when interpreting results.
What This Means for CRC Screening
The takeaway is clear: FITs are great at finding distal advanced adenomas but less so for proximal ones. QRAs, while not perfect, have more balanced detection rates. To improve CRC screening effectiveness, experts need to find ways to boost proximal adenoma detection—whether by combining FITs with other tests, refining QRAs to better capture proximal risk factors, or using colonoscopy (the “gold standard”) for high-risk groups.
This study was published in the Chinese Medical Journal in 2021 by Hong-Da Chen, Ming Lu, Yu-Han Zhang, and Min Dai. The full study is available at doi.org/10.1097/CM9.0000000000001346.
Colorectal cancer screening saves lives—but as this research shows, not all tools work the same for every part of the colon. By understanding these differences, doctors and public health experts can tailor screening to catch more adenomas, earlier.
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