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Dr Semaan on Liquid Biopsy vs Tissue Biopsy for Detecting Sarcomatoid RCC

Karl Semaan, MD, MSc, discusses the clinical advantages of liquid biopsy over tissue biopsies in detecting sarcomatoid renal cell carcinoma.

Karl Semaan, MD, MSc, postdoctoral research fellow, Dana-Farber Cancer Institute, discusses the clinical advantages of liquid biopsy epigenomic profiling for detecting sarcomatoid renal cell carcinoma (RCC) compared with traditional tissue biopsy.

Semaan explains that sarcomatoid features in RCC are often heterogeneous and may not be uniformly present throughout the entirety of the primary tumor or its metastases, making isolated tissue biopsy samples a less accurate diagnostic tool for detecting these features. This heterogeneity poses a significant challenge, as sampling from a non-representative region of the tumor may miss the presence of sarcomatoid components, leading to an incomplete or inaccurate diagnosis, he notes.

At the 2024 Kidney Cancer Research Summit, Semaan and colleagues presented early findings on a liquid biopsy assay developed using chromatin immunoprecipitation and sequencing for H3K27ac. Findings indicated that the assay displayed an area under the receiver operating characteristic curve of 0.92 for classifying plasma samples, showing its potential to overcome the tumor heterogeneity that makes detecting sarcomatoid features difficult with other approaches.

Semaan highlights that the primary benefit of liquid biopsy lies in its ability to capture a comprehensive overview of the tumor burden across the entire body. The liquid biopsy assay has the ability to detect circulating tumor DNA (ctDNA), which is shed into the bloodstream from all tumor sites, he says.

The assay's ability to capture aggregate ctDNA throughout the body reflects its capability to better define the totality of the tumor's genetic and epigenetic profile across metastatic sites and the primary tumor if nephrectomy has not yet been performed, Semaan says. This comprehensive profiling enhances the sensitivity of detecting sarcomatoid-specific signals, which are crucial for diagnosing patients and guiding treatment decisions, Semaan explains.

Liquid biopsy assays offer clinicians a clinical advantage in the detection of sarcomatoid features in RCC compared with tissue biopsy samples, and by gaining a more comprehensive and representative molecular assessment of the tumor burden, liquid biopsy could improve diagnostic accuracy, optimize therapeutic strategies, and ultimately enhance patient care in cases where traditional tissue biopsy may fall short, Semaan concludes

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