e16572 Background: Detectable circulating tumor DNA (ctDNA) in patients with metastatic urothelial cancer (mUC) is associated with poor outcomes. Whether quantitative ctDNA values confer independent prognostic information beyond conventional parameters is unclear. Methods: We retrospectively analyzed patients with mUC (urothelial carcinoma UC, variant, or mixed histology) treated at our institution who had ctDNA measured using the tumor-informed Signatera assay within 21 days prior to initiating a line of systemic therapy. Patients could contribute multiple treatment lines. ctDNA levels were reported as mean tumor molecules per milliliter (MTM/ml). The primary endpoint was overall survival (OS) from therapy initiation. Cox proportional hazards models evaluated baseline ctDNA as: (1) a quantitative continuous variable (log10-transformed), and (2) a qualitative binary variable (detectable vs. undetectable). Univariate and multivariable models estimated hazard ratios (HRs) with 95% confidence intervals (95% CIs). Multivariable models were adjusted for line of therapy, therapy class, Karnofsky Performance Status (KPS) 1 indicates increased risk of death. Model HR (95% CI) P-value Unadjusted 2.6 (1.5–4.4) <0.001 Adjusted for line of therapy 2.6 (1.5–4.3) <0.001 Adjusted for KPS 2.6 (1.5–4.5) 0.001 Adjusted for visceral metastases 2.7 (1.5–4.9) <0.001 Adjusted for therapy class 2.4 (1.4–4.2) 0.001 Fully adjusted 3.0 (1.5–5.8) 0.002
Karol et al. (Thu,) studied this question.