IBCN 2018: Longitudinal Assessment of Multiplex Patient-Specific ctDNA Biomarkers in Bladder Cancer for Diagnosis, Surveillance, and Recurrence.
Rotterdam, The Netherlands (UroToday.com) The use of circulating tumor DNA (ctDNA) as a biomarker for disease staging at diagnosis, treatment response, and recurrence monitoring is an emerging field. In bladder cancer, the utility of ctDNA has shown promising results. Using a prospective cohort of 68 muscle-invasive bladder cancer (MIBC) patients treated with neoadjuvant chemotherapy, a panel of 16 tumor-specific mutations was designed (SignateraTM RUO) based on whole-exome sequencing of tumor and germline DNA. In total, we analyzed ctDNA from longitudinally collected plasma samples from 637 time points procured at diagnosis, during treatment, at cystectomy, and during monitoring until disease recurrence or up to 2 years follow-up. Results of the ctDNA analyses were compared to radiographic imaging and clinical outcomes. ctDNA from longitudinally-collected urine samples will also be analyzed for treatment response and disease recurrence. Results from the first 50 patients showed plasma ctDNA status was strongly prognostic of recurrence-free survival at diagnosis. Specifically, 62% (8/13) of the ctDNA+ patients at diagnosis recurred after neoadjuvant treatment and cystectomy; conversely, none (0/22) of the ctDNA- patients recurred (p<0.0001). In addition, a strong correlation was also observed between the presence of ctDNA after cystectomy and disease relapse. Specifically, relapse after cystectomy was detected in 100% (10/10) of ctDNA+ patients ~120 days (0–245 days) prior to radiographic imaging, while 0% (0/38) of ctDNA- patients relapsed (p<0.0001).
In summary, they showed a strong prognostic potential of ctDNA in bladder cancer at the time of diagnosis, suggesting a potential role for ctDNA in the staging of bladder cancer. Incorporation of ctDNA analysis into routine follow-up may allow earlier initiation of alternative treatment modalities. Further external validation and cost comparison of ctDNA versus other biomarkers are needed.
Presented by: Karin Birkenkamp-Demtröder, MSci, Ph.D., Clinical Research Unit, Aarhus University Hospital, Aarhus, Denmark
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