Abstract 1962: Detection of plasma circulating tumor DNA is not affected by kidney and liver function in patients with muscle-invasive bladder cancer

Abstract Introduction: Circulating tumor DNA (ctDNA) has demonstrated significant potential for early relapse detection and therapeutic monitoring in patients with muscle-invasive bladder cancer (MIBC). Advancing its clinical utility requires examining factors that may affect plasma ctDNA levels, including those influencing clearance. Here, we evaluated the association between plasma ctDNA detection and kidney and liver function markers in MIBC patients. Secondly, we explored the association between plasma ctDNA detection and immune markers, as well as the prognostic potential of the evaluated biochemical markers. Methods: Tumor-informed plasma ctDNA analysis was available for 276 MIBC patients undergoing radical cystectomy (RC), of which 174 patients received neoadjuvant chemotherapy (NAC). Biochemical measurements collected within 10 days of an available ctDNA test (median: 0 days [IQR: 0-2 days]) and clinical data were retrieved from the patients’ electronic health records. Immune marker measurements were confined to the pretreatment period. The median levels of all biochemical markers were within normal reference ranges, except for the neutrophil-to-lymphocyte ratio (NLR) which was above normal range in ctDNA positive patients. Wilcoxon rank-sum test, Spearman’s correlation and Bonferroni correction for multiple testing were applied. Results: The primary analysis indicated no correlation between kidney (plasma creatinine, eGFR) and liver (albumin, lactate dehydrogenase, alanine aminotransferase (ALAT), bilirubine, alkaline phosphatase) function markers in MIBC patients and plasma ctDNA detection or ctDNA variant allele frequencies (VAFs). Subgroup analyses of NAC-treated and NAC-naïve patients showed similar results, with no association observed, except for a weak positive correlation between ALAT and plasma ctDNA detection in NAC-naïve patients (P=0.036, n=72; not significant after multiple test correction). Levels of leukocytes (P=0.00098, n=146), neutrophils (P=0.0004, n=134), NLR (P=0.00016, n=77) and C-reactive protein (P=0.04, n=241), demonstrated positive correlations with plasma ctDNA detection. Multivariable logistic regression including tumor stage at diagnosis confirmed significant correlations between ctDNA detection and leukocytes (P=0.00322, n=146), neutrophils (P=0.00152, n=134) and NLR (P=0.00185, n=77). None of the biochemical parameters were associated with pathological downstaging after NAC. Reduced pretreatment plasma lymphocyte levels correlated with recurrence in the NAC-treated patients (P=0.012; not significant after multiple test correction). Conclusion: Clinical application of ctDNA can be implemented with minimal risk of detection being influenced by fluctuations in the patients’ kidney and liver function. Finally, biochemical parameters alone showed no strong prognostic value. Citation Format: Deema Radif, Sia V. Lindskrog, Iver Nordentoft, Karin Birkenkamp-Demtröder, Mads Agerbæk, Jørgen B. Jensen, Lars Dyrskjøt. Detection of plasma circulating tumor DNA is not affected by kidney and liver function in patients with muscle-invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1962.