KIDNEY-PAGER: analysis of circulating tumor DNA as a biomarker in renal cancer – an observational trial. Study protocol
DOI:
https://doi.org/10.2340/1651-226X.2024.25581Keywords:
Renal cell carcinoma, translational research, biomarkers, circulating tumor DNA, risk stratification, minimal residual disease, liquid biopsyAbstract
Background: Management of localized renal cell carcinoma (RCC) is challenged by inaccurate methods to assess the risk of recurrence and deferred detection of relapse and residual disease after radical or partial nephrectomy. Circulating tumor DNA (ctDNA) has been proposed as a potential biomarker in RCC.
Purpose: Conduction of an observational study to evaluate the validity of ctDNA as a biomarker of the risk of recurrence and subclinical residual disease to improve postoperative surveillance.
Material and methods: Urine and blood will be prospectively collected before and after surgery of the primary tumor from up to 500 patients until 5 years of follow-up. ctDNA analysis will be performed using shallow whole genome sequencing and cell-free methylated DNA immunoprecipitation sequencing. ctDNA levels in plasma and urine will be correlated to oncological outcomes. Residual blood and urine as well as tissue biopsies will be biobanked for future research.
Interpretation: Results will pave the way for future ctDNA-guided clinical trials aiming to improve RCC management.
Downloads
References
Leibovich BC, Blute ML, Cheville JC, et al. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. Cancer. 2003;97:1663–71. https://doi.org/10.1002/cncr.11234 DOI: https://doi.org/10.1002/cncr.11234
Azawi NH, Tesfalem H, Mosholt KSS, et al. Recurrence rates and survival in a Danish cohort with renal cell carcinoma. Dan Med J [Internet]. 2016;63. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27034180 [cited: 2023-11-08]
Larribère L, Martens UM. Advantages and challenges of using ctDNA NGS to assess the presence of minimal residual disease (MRD) in solid tumors. Cancers. 2021;13:5698. https://doi.org/10.3390/cancers13225698 DOI: https://doi.org/10.3390/cancers13225698
Corcoran RB, Chabner BA. Application of cell-free DNA analysis to cancer treatment. N Engl J Med. 2018;379:1754–65. https://doi.org/10.1056/NEJMra1706174 DOI: https://doi.org/10.1056/NEJMra1706174
Geertsen L, Koldby KM, Thomassen M, Kruse T, Lund L. Circulating tumor DNA in patients with renal cell carcinoma. A systematic review of the literature. Eur Urol Open Sci. 2022;37:27–35. https://doi.org/10.1016/j.euros.2021.12.006 DOI: https://doi.org/10.1016/j.euros.2021.12.006
Smith CG, Moser T, Mouliere F, et al. Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors. Genome Med. 2020;12:23. https://doi.org/10.1186/s13073-020-00723-8 DOI: https://doi.org/10.1158/1538-7445.SABCS18-1367
Nuzzo PV, Berchuck JE, Korthauer K, et al. Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Nat Med. 2020;26:1041–3. https://doi.org/10.1038/s41591-020-0933-1 DOI: https://doi.org/10.1038/s41591-020-0933-1
Shen SY, Burgener JM, Bratman SV, De Carvalho DD. Preparation of cfMeDIP-seq libraries for methylome profiling of plasma cell-free DNA. Nat Protoc. 2019;14:2749–80. https://doi.org/10.1038/s41596-019-0202-2 DOI: https://doi.org/10.1038/s41596-019-0202-2
Diaz de Leon A, Pirasteh A, Costa DN, et al. Current challenges in diagnosis and assessment of the response of locally advanced and metastatic renal cell carcinoma. Radiographics. 2019;39:998–1016. https://doi.org/10.1148/rg.2019180178 DOI: https://doi.org/10.1148/rg.2019180178
Lyskjær I, Iisager L, Axelsen CT, Nielsen TK, Dyrskjøt L, Fristrup N. Management of renal cell carcinoma: promising biomarkers and the challenges to reach the clinic. Clin Cancer Res. 2023. https://doi.org/10.1158/1078-0432.CCR-23-1892 DOI: https://doi.org/10.1158/1078-0432.CCR-23-1892
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2024 Laura Iisager, Johanne Ahrenfeldt, Anna Krarup Keller, Tommy Kjærgaard Nielsen, Niels Fristrup, Iben Lyskjær
This work is licensed under a Creative Commons Attribution 4.0 International License.
