In Reply Our study¹ adjusted the FIT cutoff to yield the same overall positivity rate as reported for the mt-sRNA test (17%) to enhance comparability of diagnostic performance of both tests. Below we address each of the 3 points made by Drs Yang and Ma.

First, Yang and Ma state that the recalibration of the FIT could have led to more unnecessary colonoscopies among younger adults. Although this is certainly true, the concern of unnecessary colonoscopies among younger adults would equally apply to the mt-sRNA test, for which a positivity rate of 14.2% in the 45- to 49-year age group was reported. With the adjusted cutoff of the FIT, yielding an overall positivity rate of 17% in our study population, the positivity rate in the 45- to 49-year age group was 13.8%, ie, even slightly lower than reported for the mt-sRNA test in this age group. These results suggest that the rate of unnecessary colonoscopies among younger adults would be comparable for the mt-sRNA test and the FIT with the lower positivity threshold.

Second, there were good reasons for classifying large SSLs and HPs as medium-risk adenomas rather than advanced neoplasia in the mt-sRNA test study, as outlined in the original article on that study.² According to Table 2 in that article, the sensitivity of the mt-sRNA test for detecting SSLs or HPs larger than 1 cm was as low as 17.2%, and classifying these lesions as advanced adenomas would have lowered the sensitivity for advanced adenomas from 45.9% to 39.0%.

Third, it is not surprising that people may prefer stool-based screening every 3 years over annual stool-based screening. Given that equivalent sensitivity and specificity as reported for multitarget genetic stool testing could be achieved with FIT-based screening by lowering the FIT positivity threshold, there is no clear reason why shorter screening intervals and more frequent screening would be required for FIT-based screening than for multitarget genetic stool testing. It appears plausible that the same patient preferences would be expected for FIT and multitarget genetic stool testing when both tests are recommended and offered with the same screening intervals and comparable ease of application. Under such circumstances, additional factors, such as costs, require careful consideration. Per-sample costs for the multitarget genetic stool test are more than 20-fold higher than those for FITs (approximately $600 vs $25).^3,4

Corresponding Author: Hermann Brenner, MD, MPH, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany (h.brenner@dkfz.de).

Published Online: October 24, 2024. doi:10.1001/jama.2024.18538

Conflict of Interest Disclosures: Dr Brenner reported receiving grants from the German Research Foundation (DFG), the German Federal Ministry of Education and Research, and German Cancer Aid. No other disclosures were reported.