Clinical Fellow University of North Carolina at Chapel Hill, United States
Background: For patients with clinical T1 renal masses, renal mass biopsy (RMB) yields pathologic information but has limited ability to identify patients with high-risk disease. We hypothesize that genomic characterization of biopsy specimens may improve RMB prognostic performance. This study seeks to evaluate how accurately prospectively collected RMB tissue can identify DNA mutations present in nephrectomy specimens.
Methods: From October 2018–June 2022, patients with new clinical T1 kidney tumors were enrolled onto GRADE-SRM (Genomic Risk Assessment and Decisional Evaluation for Small Renal Masses), a comparative, non-randomized hybrid trial assessing decision-making experience and cancer genomics. Patients underwent standard clinical counseling and, tissue from surgery, RMB, and germline DNA was obtained for genomic analysis. Targeted exon sequencing was performed using UNCseq v10.2 platform and variants were filtered using standard criteria. Mutation concordance was defined as percent of mutations in nephrectomy specimen also identified in the biopsy.
Results: Of 43 patients who underwent both RMB and surgery, 14 patients with ccRCC had tissue from both procedures collected and used for analysis. The median number of mutations in nephrectomy specimens was 11 compared to 10 in RMB specimens. Mutation concordance between paired nephrectomy and RMB specimens ranged from 0%-83% (mean 34%, SD 28%). Multifocal samples from nephrectomy specimens generally demonstrated a higher concordance to nephrectomy specimens (16%-100%; mean 67%, SD 26%).
Conclusions: In this study, mutational concordance between nephrectomy and RMB specimens ranges from 0-83%. These results highlight that additional sampling may be necessary to use prognostic information from RMB to guide clinical decision-making. Future research will focus on evaluating the concordance of known RCC driver mutations and investigating transcriptomic similarities between RMB and nephrectomy specimens.
