Two strands of clinical work this week reinforced circulating tumor DNA’s (ctDNA) expanding role: exploratory ctDNA‑guided therapy data in muscle‑invasive bladder cancer and conference analyses stressing the need for randomized data in breast cancer. Investigators reported actionable readouts for ctDNA in bladder cancer that are informing trial design and therapeutic stratification. At the San Antonio Breast Cancer Symposium, researchers summarized that ctDNA assays are increasingly useful for monitoring minimal residual disease and predicting outcomes, but panel sensitivity and randomized trial design remain limiting factors for routine clinical implementation. Presenters urged narrower patient populations and carefully chosen endpoints for future ctDNA‑guided trials. Taken together, the reports show momentum for ctDNA as a decision tool across tumor types while underlining the need for more sensitive assays and prospective, randomized validation to move from biomarker to standard‑of‑care.