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Published on: January 22, 2013
High Sensitivity Circulating Tumor-DNA Assays in Renal Cell Carcinoma-Are we there yet?
Fady Sidhom1, Shefali Patel1, Arpita Desai2
1University of Alabama at Birmingham, O'Neal Comprehensive Cancer Center, Birmingham, Alabama, USA.
Abstract:
As therapeutics in renal cell carcinoma (RCC) continues to advance with approval of novel treatments and recently, adjuvant therapy, the need for highly sensitive tests that go beyond traditional methods to measure disease is becoming more crucial. Tumor informed high sensitivity circulating tumor DNA (ctDNA) assays originally developed for detection of minimal residual disease (MRD) theoretically could be utilized for initial detection of occult disease but also potentially for risk and response assessment in the management of advanced RCC. There are concerns related to the sensitivity of ctDNA based assays in RCC. This article aims to summarize the available evidence for high sensitivity MRD assays in RCC. We included studies with both localized and metastatic stages of RCC. The studies show a varying sensitivity depending on disease settings but a high specificity (∼100%) regardless. Detectable ctDNA appeared to be a significant negative prognostic risk factor for subsequent progressive disease. ctDNA may provide significant lead time allowing physicians to adapt therapy. Several high sensitivity assays with novel analytic approaches are in development for solid tumors including RCC.
Insights
High sensitivity circulating tumor DNA (ctDNA) assays show promise for detecting renal cell carcinoma (RCC) and assessing disease progression. While sensitivity varies, ctDNA is a strong negative prognostic factor, potentially guiding treatment adaptation.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Renal cell carcinoma (RCC) therapeutics are advancing, necessitating more sensitive disease detection methods beyond traditional approaches.
- High sensitivity circulating tumor DNA (ctDNA) assays, initially for minimal residual disease (MRD), offer theoretical potential for early detection and management of RCC.
- Concerns exist regarding the sensitivity of ctDNA assays specifically within the context of RCC.
Purpose of the Study:
- To review and summarize existing evidence on the utility of high-sensitivity MRD assays in renal cell carcinoma (RCC).
- To evaluate the performance of ctDNA assays across different stages of RCC, including localized and metastatic disease.
Main Methods:
- Systematic review of studies investigating high-sensitivity MRD assays in RCC.
- Inclusion of studies encompassing both localized and metastatic stages of renal cell carcinoma.
- Analysis of ctDNA detectability, sensitivity, specificity, and prognostic value.
Main Results:
- ctDNA assays demonstrate high specificity (approximately 100%) in RCC across various disease settings.
- Assay sensitivity varies depending on the specific disease stage and assay characteristics.
- Detectable ctDNA was identified as a significant negative prognostic factor for disease progression in RCC patients.
Conclusions:
- High-sensitivity ctDNA assays hold potential for early detection, risk stratification, and response assessment in RCC management.
- ctDNA detectability can provide a crucial lead time for therapeutic adaptation in advanced RCC.
- Ongoing development of novel, high-sensitivity ctDNA assays promises improved utility for solid tumors, including RCC.
