ASTRO 2020: Predicting Survival Outcomes in Bladder Cancer Using Urinary Tumor DNA
Posted: Tuesday, November 10, 2020
Within a small cohort of patients with muscle-invasive bladder cancer, detecting mutations within preoperative urinary cell-free DNA seemed to be more predictive of progression- free survival than surgical pathologic complete response. Ramandeep K. Babbra, MD, of Washington University School of Medicine, St. Louis, and colleagues presented the findings of this noninvasive liquid biopsy study at the 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 4129).
Researchers first established the stability of storing urinary cell-free DNA within a solution of 10 mM EDTA (ethylenediaminetetraacetic acid) for 7 days. They then created a 387 kb panel targeting 494 genes, including several “hotspot” regions in bladder cancer described by The Cancer Genome Atlas as well as DNA damage response genes. The panel was applied to blood plasma samples and both the pellet and supernatant of centrifuged urine samples. Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) was then performed on 12 urine samples from patients with muscle-invasive bladder cancer collected on the day of radical cystectomy.
CAPP-Seq analysis of the urinary cell-free DNA samples produced an average selector on-target rate of 60.6% compared with 52.6% in plasma cell-free DNA. In the 12 patients undergoing radical prostatectomy, CAPP-Seq duplex variant-calling from the preoperative urine supernatant samples revealed detectable urinary tumor DNA variants in four of the seven patients who did not achieve a pathologic complete response. Urinary tumor DNA variants were also detected among two of the five patients who had achieved a pathologic complete response. None of these detectable mutations were seen in the matched germline samples.
Progression-free survival was strongly associated with detection of urinary tumor DNA (P = .03, hazard ratio = 12.9), more so than pathologic complete response (P = .19, hazard ratio = 4.9). Overall survival was not significantly correlated with either pathologic response status or urinary tumor DNA detection, which researchers attributed to the short follow-up time and small cohort size.
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