e17100 Background: Despite extensive work to characterize genomic alterations (GAs) in metastatic renal cell carcinoma (mRCC), GAs are not currently used for treatment sequencing or selection. Circulating tumor DNA (ctDNA) in both blood and urine may elucidate potential mRCC biomarkers through a minimally invasive approach. We aimed to validate previous blood-based ctDNA studies (Pal et al Eur Urol 2017) and compare detection rates of clinically relevant GAs in plasma and urine. Methods: From a single institution, patients (pts) with mRCC were recruited to provide a plasma and urine specimen. ctDNA next-generation sequencing was performed using an investigational 120-gene panel, and we limited our assessment to 7 GAs with biological relevance in RCC ( VHL, MTOR, PIK3CA, TSC2, MET, AKT1, TSC1). Further, only pathogenic alterations previously recognized in RCC and cited in the Catalogue of Somatic Mutations in Cancer (COSMIC) database were considered. Clinicopathologic variables, treatment type and response to therapy were collected from an institutional mRCC patient database. Concordance analysis was performed at the gene level between blood and urine using previously published approaches (Chae et al Oncotarget 2016). Results: 50 pts (40M:10F) were enrolled with a median age of 65. 40 pts (80%) had clear cell histology, while the remainder were papillary (12%), chromophobe (4%) or other (4%). Pts received a median of 1 line of therapy (range, 0-7). GAs were identified in 45 pts (90%) in blood and in 45 pts (90%) in urine . Applying the above criteria, the most frequently observed GAs in blood specimens were TSC2 (9%), MTOR (4%), and VHL (2%). The most frequently observed GAs in urine were VHL (4%) and MTOR (2%). The rate of concordance between blood- and urine-detected GAs was 93%. Of pts bearing mTOR pathway alterations in blood or urine, 3 received everolimus-based therapy. All 3 pts remain on therapy at 10.4, 13.8 and 14.0 months, respectively. Conclusions: Biologically relevant GAs can be detected in pts with mRCC using blood and urine. Our methodology showed high concordance between both platforms. Consistent with prior reports, ctDNA assessment of pts with pretreated mRCC shows a higher frequency of TOR pathway alterations and a lower frequency of VHL mutation.
Cell-free Circulating Tumor DNA (ctDNA) in Metastatic Renal Cell Carcinoma (mRCC): Current Knowledge and Potential Uses
