Abstract 2423: Linking liquids: cfDNA in urine and plasma as informative allies in metastasized prostate cancer

Abstract Background: Liquid biopsy has become a cornerstone of non-invasive cancer diagnostics. While the major analyte for detecting and monitoring tumors has been blood, examining other body fluids, such as urine or saliva, is increasingly shifting into focus. Urine is a particularly valuable specimen due to its easy accessibility. Particularly in urologic cancers, the sensitivity of liquid biopsy could be improved by proximal sampling. While there is already evidence that cell-free DNA from urine (ucfDNA) can add to the diagnostic sensitivity in renal and bladder cancer, less is known about ucfDNA in prostate cancer patients. In this study, we aimed to determine the presence, levels, and potential clinical applications of ucfDNA in patients with metastatic prostate cancer. Moreover, we compared the findings with information obtained from plasma cell-free DNA (cfDNA). Methods: Urine was collected and stabilized using the PAXgene Urine Liquid Biopsy Set or STRECK as a preservative. The collection and stabilization using PAXgene Urine Liquid Biopsy Set allows a standardized collection and stabilization of urine with fixed volumes of urine and preservatives. Blood was collected in PAXgene Blood ccfDNA Tubes (PreAnalytiX). Matched blood and urine cfDNA samples from 122 metastatic prostate cancer patients were isolated using the QIAsymphony platform. Tumor fraction and presence of somatic copy number alterations (SCNA) were assessed from shallow whole genome sequencing data using the ichorCNA algorithm. Results: In 22/122 (18%) of patients SCNAs could be detected in both, urine and blood. Although the copy number profile was highly concordant in those patients, tumor fractions varied between plasma and urines on an individual patient level. In addition, in 52/122 (43%) and 48/122 (39%) patients, tumor-derived DNA was detected only in plasma or urine. Considering the entire cohort, neither the absolute cfDNA concentration nor tumor fraction did significantly differ between urine and plasma samples. Conclusion: Our data demonstrate that ucfDNA can provide complementary information to blood about prostate tumors, which would be missed by the sole analysis of plasma cfDNA. Taking this into account and adding that urine represents a non-invasive specimen type that can be collected at great ease, ucfDNA holds promise in the clinical management of prostate cancer. Citation Format: Tina Moser, Anna Eberhard, Matthias J. Moser, Lisa Glawitsch, Sabrina Hammer, Georgios Vlachos, Isaac Lazzeri, Leandra Ziegler, Emil Bauernhofer, Nina Monsberger, Jochen B. Geigl, Thomas Bauernhofer, Ellen Heitzer. Linking liquids: cfDNA in urine and plasma as informative allies in metastasized prostate cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2423.