“…However, these ultrasensitive assays would add operational complexity (i.e., archival tissue block retrieval and cancer genotyping) and exclude patients for whom tumor tissue is unavailable; ultimately it is plausible that more granular stratification of the ctDNA < 2% subgroup may offer diminishing returns for prognostication in advanced disease where ctDNA is relatively abundant. Conversely, measuring ctDNA% in the range of 2–100% is readily achieved via a variety of existing panel-based de novo genotyping strategies 23 , 29 , 57 , 58 , including assays that have been deployed across recent phase II-III mCRPC trials 16 , 30 , 59 – 61 . In future, continued improvements in methodological transparency and acknowledgement of test limitations will be important for truly optimized ctDNA% testing, and ultimately end-users should still be aware of factors such as clonal-hematopoiesis and tumor aneuploidy that can cause erroneous ctDNA% readouts 26 , 33 .…”