ctDNA predicts clinical T1a to pathological T3a upstaging after partial nephrectomy

Area of Science:

• Urology
• Oncology
• Molecular Diagnostics

Background:

• Clear cell renal cell carcinoma (ccRCC) often presents as early-stage tumors (cT1a).
• A significant number of cT1 RCC patients experience pathological upstaging to pT3a, correlating with poorer outcomes.
• Current use of circulating tumor DNA (ctDNA) in RCC is primarily for monitoring treatment response and resistance.

Purpose of the Study:

• To investigate the potential of ctDNA as a preoperative predictor for pT3a upstaging in cT1a ccRCC.
• To correlate ctDNA detection with tumor complexity and pT3a upstaging in ccRCC patients.

Main Methods:

• Plasma samples from 48 cT1a ccRCC patients undergoing partial nephrectomy were analyzed for ctDNA.
• ctDNA profiles were compared with clinicopathological features, including tumor complexity assessed by anatomical classification.
• Statistical analyses included univariate (chi-squared, t-tests) and multivariate approaches.

Main Results:

• 12 out of 48 (25%) patients were upstaged to pT3a.
• ctDNA was detected in 20.8% of patients, primarily those with renal sinus fat invasion (SFI).
• ctDNA was detected in 75% of pT3a patients versus 2.8% of pT1a patients, with detection being the sole significant preoperative predictor of pT3a upstaging.

Conclusions:

• ctDNA shows potential as a non-invasive, preoperative biomarker for predicting pT3a upstaging in cT1a ccRCC.
• The presence of ctDNA, particularly in the context of SFI, is strongly associated with pathological upstaging.
• This study pioneers the use of ctDNA for preoperative risk stratification in early-stage ccRCC.