FIT Outperforms Blood-Based cfDNA Test in Detecting Precancerous Colorectal Lesions

A widely used fecal immunochemical test (FIT) significantly outperformed a novel blood-based cell-free DNA (cfDNA) test in detecting advanced precancerous colorectal lesions (APCL) in colorectal cancer (CRC), a comparative study published in Cancer Communications found.¹ The study raises important considerations for current and future CRC screening strategies, according to the authors.

The authors emphasized the need for further research into improving the diagnostic performance of both blood- and stool-based tests, particularly to enhance early lesion detection. | Image credit: SewcreamStudio - stock.adobe.com

Screening is among the most effective colon cancer prevention strategies, the authors explained, but patient adherence to screening remains a significant challenge. Although blood-based tests are easier to implement in routine practice compared with endoscopic screening or FIT testing, they historically could not compete with the neoplasm detection rates seen with the endoscopic or FIT screening. A novel cfDNA test, Guardant’s Shield, which received a green light from the FDA in July 2024, was the first blood-based screening to be FDA approved and was shown to be effective in the ECLIPSE study (NCT04136002).²

The new research, led by scientists at the German Cancer Research Center, compared diagnostic performance between the FDA-approved cfDNA blood test assessed in ECLIPSE and the FIT test used in the German BLITZ study, both of which enrolled large screening populations undergoing colonoscopy. Data from 7861 patients in the ECLIPSE study and 5683 patients in the BLITZ study were included in the analysis, which applied exclusion criteria similar to those in the ECLIPSE study to the BLITZ population to match the populations as closely as possible. Both studies showed similar participant demographics and CRC detection rates (0.8%), although APCL prevalence was slightly higher in ECLIPSE (14.2% vs 10.3%).

Regarding performance metrics, FIT had significantly higher sensitivity for APCL (31.5%) compared with the cfDNA test (13.2% vs 31.5%; P < .001). FIT also demonstrated a higher sensitivity for combined detection of CRC and APCL (35.4% vs 17.0%; P < .001), as well as better specificity (93.3% vs 89.6%; P < .001).

Sensitivity for CRC detection alone was comparable between the 2 modalities—88.6% for FIT vs 83.1% for cfDNA (P = .597). For stage I to III CRC, cfDNA and FIT showed similar sensitivity (87.5% vs 86.5%, respectively).

Considerations for CRC Screening Programs

The authors highlighted that sensitivity to detect APCL is a key determinant of long-term effectiveness in CRC screening, as early detection of precancerous changes is essential for cancer prevention.

“A potential advantage of blood-based tests could be easier implementation and higher adherence in routine medical practice,” they wrote. “However, the apparent disadvantage in adherence of stool-based tests such as the FIT may be effectively overcome at comparatively much lower costs by well-organized screening programs, as meanwhile convincingly demonstrated in multiple countries, such as the Netherlands or Denmark.”

A recent modeling study also supported the superior cost-effectiveness of FIT even when assuming lower participation compared with blood-based screening,³ further strengthening its standing as the preferred noninvasive option.

“Taken together, for the time being, efforts to achieve high adherence in well-organized FIT-based programs appear the more promising approach to enhance the impact of noninvasive CRC screening on the population level,” the authors wrote. “However, further research should aim to enhance diagnostic performance of both blood- and stool-based tests, in particular with respect to the detection of APCLs.”

The authors emphasized the need for further research into improving the diagnostic performance of both blood- and stool-based tests, particularly to enhance early lesion detection.

The study’s main limitation was its reliance on indirect comparison between 2 separate populations, the authors explained. While they attempted to closely match inclusion and exclusion criteria, subtle differences in demographics or colonoscopy quality could have influenced the results. Direct head-to-head studies are needed to eliminate such confounding variables, they noted.

“In conclusion, further major improvement in diagnostic performance is needed for the cfDNA blood-based test to become a competitive alternative for noninvasive CRC screening,” the authors wrote. “Major efforts to enhance sensitivity of this and alternative ‘liquid biopsy’ approaches to detect preneoplastic lesions would be of paramount importance for efficient use in CRC screening practice.”

References

1. Seum T, Hoffmeister M, Brenner H. Cell-free DNA blood-based test compared to fecal immunochemical test for colorectal cancer screening.  Cancer Commun (Lond). Published online May 26, 2025. doi:10.1002/cac2.70037

2. Bonavitacola J. Blood test approved by FDA for screening for colorectal cancer. AJMC^®. July 29, 2024. Accessed May 30, 2025. https://www.ajmc.com/view/blood-test-approved-by-fda-for-screening-for-colorectal-cancer

3. van den Puttelaar R, Nascimento de Lima P, Knudsen AB, et al. Effectiveness and cost-effectiveness of colorectal cancer screening with a blood test that meets the Centers for Medicare & Medicaid Services coverage decision. Gastroenterology. 2024;167(2):368-377. doi:10.1053/j.gastro.2024.02.012