Antibody-based multitarget FIT may be more accurate than standard FIT

A multitarget fecal immunochemical test (FIT) could reduce colorectal cancer incidence and death and might be cost-effective, according to a recent validation study.

An antibody-based multitarget fecal immunochemical test (mtFIT) for colorectal cancer (CRC) showed better diagnostic accuracy in detecting advanced neoplasia compared with the standard FIT test because of its ability to better detect advanced adenomas without compromising specificity, a study found.

Researchers from the Netherlands used leftover FIT samples from 1,284 patients to assess whether the addition of protein biomarker quantification in stool could be used to improve the sensitivity of FIT without sacrificing specificity. Patients were classified by their most advanced lesion: CRC, advanced adenomas, advanced serrated polyps, nonadvanced adenomas, or nonadvanced serrated polyps. Researchers applied classification and regression tree analysis to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity. Results were published by Annals of Internal Medicine on July 20.

Three biomarkers, hemoglobin, calprotectin, and serpin family F member 2, had significantly higher sensitivity than standard FIT for advanced neoplasia, and equal specificity to standard FIT. For advanced neoplasia, the biomarkers had cross-validated sensitivity of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (95% CI, 30.7% to 44.2%) for FIT (P=0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (95% CI, 20.8% to 36.5%) to 37.8% (95% CI, 29.6% to 46.5%) (P=0.006).

On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT. The authors estimated that when done biennially, mtFIT would reduce CRC incidence and death by 12% and 8%, respectively, compared with traditional biennial FIT, assuming 73% adherence, which was the adherence in the Dutch FIT program. With perfect adherence, the reduction in incidence and death would improve to 17% and 11%, respectively. Finally, when the findings were applied to a validated cancer screening model, the mtFIT was found to be cost-effective up to at least $84 per test. Researchers are now preparing a Dutch CRC screening trial to further validate mtFIT, the authors noted.

An accompanying editorial stated, “Ultimately, this study offers promise of incremental but important improvements in the effectiveness of population-based CRC screening through novel biomarker measurement using an existing screening platform. … Personalized screening that takes into account these biomarkers as well as demographic characteristics, exposures (for example, tobacco), and genetic information may eventually be adopted. However, in the meantime, let's encourage ongoing efforts to optimize screening as we endeavor to continue our progress in reducing CRC incidence and death.”