Molecularly, the typically low fraction of ctDNA in RCC amplifies pre-analytical and library preparation bias, necessitating the use of unique molecular identifiers (UMIs) for error suppression, tumor-informed gene panels focusing on VHL, PBRM1, BAP1, and SETD2, and complementary methylation or fragmentomic assays. Here, PBRM1 is linked to renal cell carcinoma.