Timing and Choosing Tissue vs ctDNA Testing in Metastatic Prostate Cancer

The panelists recommend genomic profiling at the first visit for patients with metastatic prostate cancer, since targeted options now apply at diagnosis and archival tissue degrades over time, often leaving patients ineligible for trials late in their disease course. They note that oligometastatic disease detected only by PSMA PET may not yet warrant PARP inhibitors or capivasertib. Comparing assays, the panelists consider tissue the gold standard because it better detects homozygous deletions, copy number changes, and rearrangements, including BRCA2 deletions, and supports microsatellite instability, tumor mutational burden, and IHC testing. Circulating tumor DNA (ctDNA) is fast, noninvasive, repeatable, and captures heterogeneity across metastatic sites, reliably detecting point mutations in BRCA1, BRCA2, ATM, and other HRR genes when enough tumor DNA is present. However, ctDNA can miss deletions, and clonal hematopoiesis can confound ATM, CHEK2, and TP53 findings, so the panelists reserve ctDNA for patients without usable tissue.