High Sensitivity Circulating Tumor-DNA Assays in Renal Cell Carcinoma–Are we there yet?

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.