Liquid Biopsy Shows High Accuracy in Detecting Early-Stage Renal Cell Carcinoma

If validated, the investigators believe that this non-invasive test could help detect renal cell carcinoma earlier on, thereby reducing the mortality of the disease.

A novel liquid biopsy has demonstrated validity in identifying patients with renal cell carcinoma (RCC) across all stages of disease, making it easier to detect early-stage disease before it has metastasized, according to the results of a study published in Nature Medicine.1,2

If validated, the investigators believe that this non-invasive test could help detect RCC earlier on, thereby reducing the mortality of the disease.

“Hopefully we can scale this to a much larger level and detect cancer earlier so we can act earlier,” co-senior study author Toni Choueiri, MD, the director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, said in a statement.

Currently, no screening method is FDA-approved or recommended for the detection of RCC in the general population. The study authors suggested that this assay could potentially be used initially as a screening test for people who have a family history of kidney cancer or who previously had kidney cancer. “We need to be specific first, before making it totally mainstream,” Choueiri said.

RCC sheds the least amount of cell-free DNA (cfDNA) of all extracranial tumors so cfDNA-based methods alone are insufficient for detecting RCC. Further, genomic alteration–based plasma cfDNA testing has identified fewer than 80% of patients with advanced RCC in prior studies. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq), on the other hand, has shown efficacy in identifying RCC from among other tumor types and healthy controls.

The investigators used a cfMeDIP-seq approach on plasma and urine cfDNA to detect RCC, which was the first such application of cfMeDIP-seq on urine cfDNA for cancer detection.

“Kidney cancer is one of the hardest tumors to detect, because it doesn’t shed as much DNA as other tumors,” said Matthew Freedman, MD, a medical oncologist at Dana-Farber Cancer Institute and co-senior author of the report, in a statement. “That’s where this test performs really well…. And it’s a proof of principle that early stage disease is detectable.”

Testing was performed on 148 samples, including 99 from cases of stage I to IV RCC, 21 samples of stage IV urothelial bladder cancer, and 28 samples from healthy, cancer-free controls.2

Across the training test sets, RCC samples had a higher median methylation score than control samples and had a mean area under the receiver operating characteristic (AUROC) curve of 0.990 (95% CI, 0.985-0.995). Among urine cfDNA samples, the mean AUROC for patients with RCC compared with healthy controls was 0.858 (95% CI, 0.831-0.885).

“Notably, these data were generated using a protocol optimized for plasma,” the study authors wrote in their report. “While urine-based classification was not as accurate as plasma-based classification, we believe that performance can be improved through technical and computational optimization, such as size selection of cfDNA to enrich for tumor-derived DNA and utilizing tumor methylation data to inform cfDNA methylation analysis. Nevertheless, these results highlight the potential value of urine cfMeDIP–seq for early detection of localized RCC.”

The authors noted that alone or combined with standard imaging, following further validation in larger and prospective datasets, this screening method could help to identify RCC earlier on and reduce the amount of unnecessary kidney biopsies and nephrectomies.


  1. Biomarker Test Highly Accurate in Detecting Early Kidney Cancer. News release. Dana-Farber Cancer Institute. June 22, 2020. Accessed June 24, 2020.
  2. Nuzzo PV, Berchuck JE, Korthauer K, et al. Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Nature Med. Published online June 22, 2020. doi:10.1038/s41591-020-0933-1