The Impact of Kidney, Liver, and Immune Function on Circulating Tumor DNA Detection in Muscle-invasive Bladder Cancer.

Background and objective: The kidneys and liver play key roles in the metabolism of circulating molecules, including nucleic acids. To advance the clinical utility of circulating tumor DNA (ctDNA), it is essential to examine factors potentially affecting plasma ctDNA levels, including those influencing the clearance of cell-free DNA and ctDNA. This study evaluated the associations between plasma ctDNA detection and biochemical markers indicative of kidney and liver function, and leukocyte-based immune function and inflammation in patients with muscle-invasive bladder cancer (MIBC), along with their prognostic potential.

Methods: A tumor-informed plasma ctDNA analysis was conducted for 276 MIBC patients treated at Aarhus University Hospital. Biochemical measurements collected within 10 d of available ctDNA tests were retrieved from electronic health records. Statistical analyses included multivariable logistic and linear regression models, and false discovery rate correction.

Key findings and limitations: Significant associations between kidney or liver function markers and ctDNA detection were not observed. Leukocyte count (odds ratio [OR] = 1.29 [95% confidence interval: 1.07; 1.54]), neutrophil count (OR = 1.50 [1.17; 1.92]), and neutrophil-to-lymphocyte ratio (OR = 4.01 [1.85; 8.71]) were significantly associated with ctDNA detection. Associations between biochemical parameters and pathological downstaging or recurrence were not observed. Limitations include the nonconcurrent timing of biochemical and ctDNA measurements.

Conclusions and clinical implications: This study shows no evidence that plasma ctDNA detection is affected by kidney/liver function, ensuring the reliability of using ctDNA to monitor MIBC patients. Elevated leukocyte-based immune markers were observed in ctDNA-positive patients, but the evaluated biochemical parameters showed no prognostic value. Further studies are warranted to confirm these findings.