(UroToday.com) The 2026 ASCO annual meeting featured a kidney cancer session and a presentation by Dr. Juan Ruiz Banobre discussing ultrasensitive ctDNA detection and molecular clearance as a prognostic and predictive marker in advanced RCC. RCC is characterized by exceptionally low levels of ctDNA, often falling below the limit of detection for conventional liquid biopsy assays. This low-shedding environment creates a significant unmet need for ultrasensitive strategies to detect molecular residual disease, improving patient stratification, and enabling longitudinal monitoring of disease evolution in a clinical setting.
CtDNA was profiled using NexT Personal, a tumor-informed WGS-based assay tracking up to ~1,800 patient-specific variants with a limit of detection of ~1 part per million (PPM). Baseline and longitudinal (n = 165) plasma from 37 advanced RCC patients were analyzed. The primary analysis evaluated baseline plasma (n = 36) across clinical variables. Prognostic value for progression-free survival and overall survival was assessed in patients treated with immunotherapy or TKIs (n = 35).
Baseline ctDNA was detected in 84% (31/37) of patients. Notably, 13% (4/31) of these detections occurred in the ultrasensitive range below 100 PPM. Baseline ctDNA PPM levels significantly correlated with IMDC risk group (median PPM: favorable = 10.9, intermediate = 244.2, poor = 2437.0; p = 0.005), presence of histological high-risk features (median PPM: low-risk: 40.6 versus high-risk: 1528.0; p = 0.025), and stage at diagnosis (median PPM: I-III 35.1 versus IV 1548.3; p = 0.006). Median ctDNA levels were significantly lower in patients with surgical site recurrence (5.5 versus 937.2 PPM; p = 0.038).
Molecular ctDNA clearance, defined as ctDNA-negative status at any point during first-line therapy, was highly prognostic. Molecular ctDNA clearance correlated significantly with best overall response (p = 0.007), with 100% specificity for disease control, and no patients with progressive disease achieved clearance. Patients not achieving molecular ctDNA clearance had dramatically worse progression-free survival (HR 8.69; p = 0.001) and overall survival (HR 4.70; p = 0.044). Among patients with a best response of stable disease by imaging, molecular ctDNA clearance provided critical differentiation. Those who cleared ctDNA had 100% progression free survival/overall survival at 2 years, whereas those who remained ctDNA-positive saw progression-free survival drop to 0% and overall survival to 33% by one year. Additionally, achievement of molecular ctDNA clearance was significantly associated with clinical disease control (partial response + stable disease, 92.3% versus partial response + stable disease, 50.0%; OR 12.0, 95% CI 1.32-108.8, p = 0.013).
Dr. Ruiz-Banobre concluded his presentation discussing ultrasensitive ctDNA detection and molecular clearance as a prognostic and predictive marker in advanced RCC with the following take-home points:
- Ultrasensitive ctDNA profiling effectively overcomes the low-shedding challenge of advanced RCC, and could provide additional prognostic clarity that complements standard of care imaging and IMDC risk models
- Molecular ctDNA clearance serves as an effective biomarker for long-term survival, identifying patients with durable responses even among those with radiographically stable disease
- These findings support integrating ctDNA monitoring to guide treatment intensification or de-escalation strategies
Presented by: Juan Ruiz Banobre, University Clinical Hospital Santiago de Compostela, Santiago de Compostela, Spain
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026