Below we express our concerns about the article authored by Parikh and colleagues, investigating the performance of a tumor-uninformed ctDNA assay (Guardant Health, Reveal) for MRD detection in patients with colorectal cancer (1).

The authors present a “landmark analysis” that unconventionally includes both postsurgical and postadjuvant ctDNA assessments, when the objectives of these two timepoints clearly differ; postsurgical assessments aid in determining whether or not a patient may benefit from adjuvant treatment, whereas postadjuvant assessments help determine who could benefit from further treatment. The clinical relevance of this combined “landmark analysis” can be debated. Furthermore, a direct comparison to previous reports (2, 3) that analyzed these two timepoints separately is inappropriate and misleading.

Besides the uncertain relevance of a “landmark analysis,” our major concerns lie in the apparent selection bias associated with the “longitudinal analysis” and the “surveillance analysis.” First, two patients that tested positive but...

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