Circulating Tumor DNA Assay in Non-Muscle-Invasive Bladder Cancer - Expert Commentary
The investigators conducted a retrospective study of 23 consecutive NMIBC patients who underwent serial ctDNA monitoring using the commercially available Signatera. This assay is a personalized, tumor-informed ctDNA test that uses sequencing of tumor tissue to identify 16 clonal somatic variants unique to each patient's tumor, creating a personalized polymerase chain reaction assay for longitudinal monitoring. Blood samples were collected at baseline and every 3 months for 2 years, with ctDNA positivity defined as the detection of at least two tumor-specific mutations per sample.
The cohort consisted predominantly of white (83%) males (87%) with median age of 70 years; all diagnosed with high-grade urothelial carcinoma. Notably, 22% had BCG-unresponsive disease, 17% had histological subtypes, 9% had divergent differentiation, and 22% had carcinoma in situ. ctDNA was detected in 35% of patients (8/23), and 39% ultimately underwent cystectomy. During follow-up, three patients experienced intravesical recurrences on salvage therapy, while one developed metastatic recurrence after radical cystectomy. The limitations include selection bias due to referral population enriched for BCG-unresponsive disease and high-risk pathological features, which may inflate ctDNA positivity and cystectomy rates compared to general NMIBC populations. The retrospective design introduces information bias regarding surveillance timing influenced by ctDNA results rather than standardized intervals.
Understanding the clinical and biological significance of ctDNA in patients with NMIBC is critical. Prospective validation studies are needed to establish ctDNA's role in risk stratification and treatment optimization. Future studies comparing or combining ctDNA with urine cell free DNA may help distinguish patients likely to benefit from additional intravesical therapy from those requiring early cystectomy.
Written by: Bishoy M. Faltas, MD, Chief Research Officer, Englander Institute for Precision Medicine, Gellert Family - John P. Leonard, MD, Research Scholar, Associate Professor of Medicine, Cell and Developmental Biology, Weill Cornell Medicine, New York- Presbyterian Hospital, NY
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