Natera submitted its Signatera MRD companion diagnostic (Signatera CDx) to the FDA for premarket approval as a tool to guide adjuvant Tecentriq in muscle‑invasive bladder cancer, citing Phase III IMvigor011 evidence that MRD-positive patients benefit from adjuvant immunotherapy. The PMA aims to make circulating tumor DNA MRD testing a regulated companion diagnostic to tailor adjuvant therapy. Separately, Johns Hopkins researchers developed a liquid biopsy that measures epigenetic instability in cfDNA to detect early‑stage cancers, offering a complementary approach to tumor detection that emphasizes methylation variability rather than absolute methylation levels. Both advances reflect diagnostic strategies moving from risk stratification to treatment decision-making and early detection, with direct implications for trial design, regulatory pathways, and adoption in oncology practice.