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Background: Standard treatment of localized muscle invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC); however, only 40-50% respond to NAC and approx. 50% experience relapse. Evaluation of treatment efficacy and early detection of relapse are therefore major clinical challenges. Methods: We present a clinical update of a previously described cohort of 68 patients who received NAC prior to RC (NAC cohort; Christensen et al. JCO 2019; median follow-up (FU) of 58 months) together with evaluation of a retrospectively collected cohort of 120 patients who did not receive NAC (no-NAC cohort; median FU of 71 months). Circulating tumor DNA (ctDNA) was analyzed before NAC (NAC cohort, n=63), prior to RC (NAC cohort, n=67; no-NAC cohort, n=115) and after RC (NAC cohort, n=66; no-NAC cohort, n=37) using Signatera™. RNA-seq was performed on 176 tumors. Results: Updated clinical FU for the NAC cohort showed that ctDNA-positive patients had significantly worse recurrence-free survival (RFS) compared to ctDNA-negative patients (before NAC: HR=16, 95%CI=3.6-70.5, p=0.0002; during surveillance after RC: HR=27.6, 95%CI=7.9-96.9, p Conclusion: Presence of ctDNA was associated with worse prognosis for both NAC and no-NAC treated patients. Transcriptomic analysis of primary tumors showed that anti-tumor immune responses may be associated with a particularly good outcome whereas EMT may be promoting more aggressive disease. Citation Format: Sia Viborg Lindskrog, George Laliotis, Karin Birkenkamp-Demtröder, Iver Nordentoft, Philippe Lamy, Elshaddai Z. White, Natalia Pajak, Tine G. Andreasen, Punashi Dutta, Meenakshi Malhotra, Shruti Sharma, Mark Calhoun, Adam ElNaggar, Minetta C. Liu, Mads Agerbæk, Jørgen B. Jensen, Lars Dyrskjøt. Utility of circulating tumor DNA and transcriptomic profiling in predicting outcome in muscle invasive bladder cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5600. |
