4542 Background: Kidney cancer remains one of the most aggressive and lethal urological malignancies, largely due to late-stage diagnosis and reliance on invasive tissue biopsies. To address this unmet clinical need, we developed and clinically validated the blood-based, cell-free mRNA test. By quantifying circulating tumor-derived transcripts in plasma, this assay provides rapid and precise molecular insights, supporting precision screening, early diagnosis, prognostication, and treatment monitoring. Methods: In this prospective clinical study, we evaluated real-time expression levels of 30 kidney cancer–associated genes in plasma samples from 51 subjects, including 41 patients with suspected kidney cancer and 10 healthy controls. The primary objective was to assess the diagnostic and prognostic performance of the Geneverify multi-gene blood-based expression panel. Log₂ fold-change values for individual genes were calculated relative to healthy controls and integrated to generate a composite risk score for each subject. Geneverify scores were compared with biopsy-confirmed diagnoses to assess assay sensitivity. Additional statistical analyses evaluated correlations between Geneverify scores and tumor stage, pathological grade, and treatment status. Results: All biopsy-confirmed kidney cancer cases demonstrated Geneverify scores greater than 10. Using an optimized cutoff score of 10, the assay achieved 100% sensitivity for cancer detection. While healthy controls served as the baseline reference, specificity against benign or non-malignant kidney disease could not be fully assessed due to the absence of such cases in this cohort. The majority of patients had early-stage (T1a) kidney cancer. Geneverify scores showed strong correlations with tumor stage, pathological grade, and clinical status. In patients with advanced or metastatic disease undergoing systemic therapy, Geneverify scores declined significantly over time, indicating potential utility for real-time treatment response monitoring. Conclusions: This study represents the first real-time clinical validation of a blood-based, cell-free mRNA genomic assay for kidney cancer detection. The Geneverify test demonstrated excellent diagnostic sensitivity, strong concordance with biopsy-confirmed disease, and meaningful prognostic and treatment-monitoring capabilities. These findings establish Geneverify as a powerful non-invasive alternative to tissue biopsy (based on published data 20% biopsies are false negative) for early detection and precision management of kidney cancer, with the potential to reduce invasive procedures and accelerate personalized oncology care.
Kato et al. (Wed,) studied this question.