Renal & Urology NewsCirculating Tumor DNA Can Predict Muscle-Invasive UTUC

Enhancing UTUC Treatment Stratification through Preoperative ctDNA Analysis

In a prospective study, the utility of preoperative circulating tumor DNA (ctDNA) in predicting muscle invasion in upper tract urothelial carcinoma (UTUC) showcases a significant stride toward personalized treatment approaches. This research underscores the potential of ctDNA to refine the clinical staging process, thereby guiding the judicious use of neoadjuvant chemotherapy (NAC) for improved patient outcomes.

Key Points:

• The study involved 30 patients with high-risk UTUC, analyzing plasma cell-free DNA before surgery using a comprehensive 152-gene panel and low-pass whole-genome sequencing.
• Surgical pathology comparisons revealed that patients with muscle-invasive and non-organ-confined UTUC exhibited a higher median number of plasma ctDNA variants than those with nonmuscle-invasive disease (3 vs. 0).
• Detection of at least one ctDNA variant occurred in 70% of patients, yet only 52% of these variants matched the DNA from corresponding tumor samples.
• A minimum of two panel-based plasma molecular alterations (MAs) in ctDNA significantly correlated with muscle-invasive and non-organ-confined UTUC, achieving 71% sensitivity and 94% specificity in predictions.
• Incorporating a plasma copy number burden score exceeding 6.5 enhanced the predictive sensitivity to 79%.
• The study indicates a potential shift from traditional clinical nomograms, which currently offer a 42-48% sensitivity in identifying patients who might benefit from NAC.
• Patients with at least two MAs in their ctDNA demonstrated notably lower 1-year progression-free survival (69%) and cancer-specific survival rates (56%) compared to those without such alterations.
• The findings advocate for the incorporation of preoperative ctDNA analysis in selecting high-risk UTUC patients for NAC, pointing toward a tailored treatment pathway.

“Although needing validation, this represents a clear improvement over the 42-48% sensitivity achieved using available clinical nomograms.”
– Roger Li, MD & Team, as reported in European Urology

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