Tumor-Informed Circulating Tumor DNA (ctDNA) in Locally Advanced and Metastatic Urothelial Carcinoma: A Retrospective Single-Center Cohort.

BACKGROUND

ctDNA may refine risk stratification and treatment monitoring in urothelial carcinoma, but real‑world data integrating tumor‑informed assays across disease settings remain limited. We evaluated the prognostic and monitoring utility of ctDNA in locally advanced (laUC) and metastatic urothelial carcinoma (mUC).

PATIENTS AND

METHODS

We retrospectively reviewed adults with laUC or mUC who underwent tumor‑informed ctDNA testing at a single center. Relationship between baseline ctDNA status (positive/negative) and serial kinetics with TTrP, radiographic progression‑free survival (rPFS), and overall survival (OS) were assessed using Log‑rank tests and Cox Proportional Hazards models.

RESULTS

Forty‑seven patients were included (laUC n = 24; mUC n = 23). Baseline ctDNA was detected in 16.6% of laUC and 60.8% of mUC. Median TTrP was 189 days for baseline ctDNA‑positive versus 553 days for ctDNA‑negative patients; in mUC, baseline ctDNA positivity was associated with shorter TTrP (Log‑rank P = .037). Absolute baseline ctDNA quantity was not associated with radiographic progression‑free survival (rPFS) (HR 1.007; P = .0518) or TTrP (HR 1.004; P = .2718). Median OS was 266 days for baseline ctDNA‑positive patients, while median OS was not reached for those with baseline ctDNA‑negative. On‑treatment decline and conversion from positive to negative were associated with improved outcomes; persistent positivity aligned with higher mortality (70% in baseline ctDNA‑positive mUC during follow‑up).

CONCLUSIONS

In this single‑center cohort, ctDNA status and on‑treatment clearance were stronger indicators of prognosis than quantitative level. Baseline positivity identified patients at increased risk of earlier progression and death, and serial kinetics provided actionable early signals in routine practice. This data supports ctDNA‑informed management across laUC and mUC.