Correlation of circulating tumor DNA (ctDNA) dynamics with clinical response in patients with muscle-invasive bladder cancer (MIBC) undergoing trimodality therapy (TMT).

e16606 Background: Trimodality therapy (TMT) is a curative treatment option for patients with muscle-invasive bladder cancer (MIBC). Plasma circulating tumor DNA (ctDNA) is associated with treatment response and clinical outcomes following cystectomy for bladder cancer, but the association of plasma ctDNA with treatment response and clinical outcomes in patients with MIBC treated with TMT is poorly understood. Methods: Select patients with MIBC who received TMT at Dana-Farber/Brigham and Women’s Cancer Center between June 2023 and January 2024 who underwent pre-TMT ctDNA evaluation with the commercially available Signatera assay were included in this analysis. Individual chart review was performed to collect demographic and clinical data including disease stage, histopathology, imaging, and treatment details. Results: Pre-treatment ctDNA results were available for 16 patients. Nine of the 16 patients had at least one post-treatment result available while the remaining 7 patients have not yet completed their first post-TMT ctDNA test. Seven of 16 patients had detectable ctDNA prior to TMT initiation. Of these 7 patients, 4 had at least one post-treatment ctDNA result available (median 11.2 weeks following TMT), and 3 of 4 patients converted to having undetectable ctDNA following TMT and were also free of disease as determined by routine post-TMT surveillance including radiographic, cytologic and cystoscopic assessment. The single patient who had persistent detectable ctDNA following TMT developed radiographic evidence of metastatic disease 3 months following TMT and died from bladder cancer 2 months later. Five patients with undetectable ctDNA prior to TMT had at least one post-TMT ctDNA result available. All five of these patients remained ctDNA-negative following TMT and have had no clinical evidence of recurrence. Conclusions: Plasma ctDNA measured using the Signatera assay can be performed in MIBC patients undergoing TMT and appears to correlate with clinical response to TMT at early time points. Larger cohorts with longer follow-up will be required to define the association between plasma ctDNA status and clinical outcomes following TMT. [Table: see text]