3245 - Correlation of Circulating Tumor DNA (ctDNA) Dynamics with Clinical Response in Muscle-Invasive Bladder Cancer (MIBC) Patients Undergoing Trimodality Therapy (TMT)

I. Epstein¹, S. Berg¹, C. Mantia¹, M. Mossanen², A. Saraf³, M. Preston², A. Ravi¹, F. L. Carvalho¹, T. Clinton², D. Roberts¹, L. C. Peng⁴, B. McGregor¹, J. Bellmunt¹, J. Berchuck¹, and K. W. Mouw⁵; ¹Dana-Farber Cancer Institute, Boston, MA, ²Brigham and Womens Hospital, Boston, MA, ³Brigham and Women’s Hospital/Dana Farber Cancer Institute, Boston, MA, ⁴Department of Radiation Oncology, Dana-Farber Brigham Cancer Center, Boston, MA, ⁵Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham & Women’s Hospital, Harvard Medical School, Boston, MA

Purpose/Objective(s): 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. We hypothesize that ctDNA dynamics are correlated with clinical outcomes in MIBC patients treated with TMT. Materials/

Methods: Select patients with MIBC who received TMT at Dana-Farber/Brigham and Women’s Cancer Center between June 2023 and February 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 18 patients. Thirteen of the 18 patients had at least one post-treatment result available while the remaining 5 patients have not yet completed their first post-TMT ctDNA test. Six of 18 patients had detectable ctDNA prior to TMT initiation. Of these 6 patients, 5 had at least one post-treatment ctDNA result available (median 7 weeks following TMT), and 3 of 5 patients converted to having undetectable ctDNA following TMT and are free of disease as assessed by routine post-TMT surveillance including radiographic, cytologic and cystoscopic assessment. Two patients had persistent detectable ctDNA following TMT: one patient with clinical T4N0 disease at diagnosis who had residual disease in the bladder following TMT and one patient who developed radiographic evidence of metastatic disease on surveillance CT scans performed 3 months following TMT. Twelve of the 18 patients had undetectable ctDNA prior to TMT, and 8 of these 12 patients had at least one post-TMT ctDNA result available. All 8 patients with undetectable ctDNA prior to TMT remained undetectable following TMT and none have had clinical evidence of recurrence.
Conclusion: 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.