CtDNA Predicts Clinical T1a to Pathological T3a Upstaging After Partial Nephrectomy

Most patients diagnosed with clear cell renal cell carcinoma (ccRCC) are also detected with small and organ-confined tumors, and the majority of these are classified as clinical tumor stage 1a (cT1a). A considerable proportion of patients with cT1 RCC shows tumor upstaging to pathological stage 3a (pT3a), and these patients have worse oncological outcomes. The role of circulating tumor DNA (ctDNA) in RCC has been limited to monitoring treatment response and resistance. Therefore, the present study aimed to evaluate the potential of ctDNA in predicting pT3a upstaging in cT1a ccRCC. We sequenced plasma samples preoperatively collected from 48 patients who had undergone partial nephrectomy for cT1a ccRCC using data from a prospective cohort RCC. The ctDNA were profiled and compared with clinicopathological ccRCC features to predict pT3a upstaging. Associations between ctDNA, tumor complexity, and pT3a upstaging were evaluated. Tumor complexity was assessed using the anatomical classification system. Univariate analysis used chi-squared and Student's t-tests; multivariate analysis considered significant factors from univariate analyses. Of the 48 patients with cT1a ccRCC, 12 (25%) were upstaged to pT3a, with ctDNA detected in 10 (20.8%), predominantly in patients with renal sinus fat invasion (SFI; n = 8). Among the pT3a group, ctDNA was detected in 75%, contrasting with only 2.8% in patients with pT1a (1/36). Detection of ctDNA was the only significant preoperative predictor of pT3a upstaging, especially in SFI. This study is the first to suggest ctDNA as a preoperative predictor of pT3a RCC upstaging from cT1a based on preoperative radiological images.