The investigators collected prospective data for 112 patients, 81% of whom were male. The median age was 71 years, and the median follow-up was 8 months. Metastatic recurrence occurred in 29% of patients and 6% had concomitant local recurrence, with a median time to progression of 6 months. During the follow-up period, 9% of patients died. There were 576 ctDNA samples overall with 53% of patients having detectable ctDNA before RC. These patients had a higher pathological stage (p < 0.001), higher rate of disease upstaging (p < 0.001), node-positive disease (p < 0.001), and variant histology on final pathology (p = 0.006). Detectable ctDNA prior to RC was associated with a worse prognosis (p < 0.0001) and was predictive of disease recurrence. Longitudinal analysis revealed that patients who had undetectable ctDNA before RC and 3 months after RC had the best prognosis, with recurrence free survival (RFS) rates of 100% at 6 months and 12 months. A subset of patients who had detectable ctDNA before RC and received definitive therapy subsequently had undetectable ctDNA status and RFS rates of 87% at 6 months and 47% at 12 months. Multivariable analyses revealed that detectable ctDNA before RC was a significant predictor of nodal involvement (OR, 5.4; 95% CI, 1.9 – 18.2; p = 0.003), locally advanced disease (OR, 3.6; 95% CI, 1.5 – 9; p = 0.005), and disease recurrence (HR, 4.5; 95% CI, 1 – 19; p = 0.04).
These findings highlight the feasibility of using ctDNA to help guide personalized treatment decisions. The variability in sensitivity and specificity of different ctDNA assays will impact predictive performance. The requirement of having sufficient tumor tissue from TURBT for ctDNA assay development is a limitation of tumor-informed assays for ctDNA measurement. As tumor-uninformed ctDNA assays improve in sensitivity and specificity, these approaches will potentially overcome this limitation and enable wider applicability in the perioperative minimal residual disease detection setting.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
References:
- Ben-David R, Tillu N, Cumarasamy S, et al. Longitudinal Tumor-informed Circulating Tumor DNA Status Predicts Disease Upstaging and Poor Prognosis for Patients Undergoing Radical Cystectomy. Eur Urol Oncol. Published online March 22, 2024. doi:10.1016/j.euo.2024.03.002