Fig. 5: Workflow for optimized clinical biomarker profiling for mCRPC incorporating ctDNA testing.

The ctDNA prediction tool (available at http://ctDNA.org) can be used to inform optimal strategy for mCRPC genomic biomarker testing, offering guidance as to whether to pursue ctDNA or tissue-based genotyping (in resource-limited circumstances where both testing modalities cannot be pursued simultaneously). Tissue-based genotyping should be initiated for patients with low predicted ctDNA%. However, ctDNA testing also offers valuable prognostic information (via ctDNA%) regardless of ctDNA%-sufficiency for sensitive genotyping, and therefore should be offered to patients if available as a prognostic adjunct (potentially in tandem with tissue-based genotyping). The tool’s output includes the probability of a sample having ctDNA ≥ 2% and a point estimate of predicted plasma ctDNA%. Finally, the ctDNA%-prediction tool is flexible to any combination of missing data as well as differences in laboratory reference range values for lactate dehydrogenase and alkaline phosphatase.