Tumor Characteristics Associated With Preoperatively Detectable Tumor-Informed Circulating Tumor DNA in Patients With Renal Masses Suspicious for Renal Cell Carcinoma

PURPOSE Understanding the specific tumor characteristics associated with detectable circulating tumor DNA (ctDNA) in patients with renal cell carcinoma (RCC) is critical for informing future studies aiming to establish the clinical utility of such testing. We characterized the pathologic and clinical features associated with preoperatively detectable ctDNA in patients with renal masses suspicious for RCC. METHODS Consecutive patients who underwent partial or radical nephrectomy for nonmetastatic suspected RCC (cT1b-T3) during 2022-2023 had prospectively collected tumor-informed ctDNA analyses conducted preoperatively and postoperatively. Descriptive statistics and univariate analyses were used to describe the study findings. RESULTS Sixty-nine patients with a median age of 62 years (IQR, 51-70) and a median follow-up time of 7 months (IQR, 3-11) had 205 ctDNA samples collected for analysis. Thirty-nine (61%) had preoperative detectable ctDNA of 64 patients. Postoperative ctDNA status was available for 47 patients, and three (6%) had detectable ctDNA. Two had inferior vena cava (IVC) involvement, and one developed metastatic disease. Subgroup analysis of solely malignant RCC (n = 65) revealed that patients with preoperative detectable ctDNA had a higher pathologic stage ( P = .001), larger tumors (7 v 4.5 cm; P = .001), higher tumor complexity ( P = .022), and increased rates of tumor grades 3-4 ( P = .038). All patients with gross renal vein or IVC involvement (n = 9) and those with lymphovascular invasion (n = 6) on pathology had detectable preoperative ctDNA. On univariate analysis, high tumor complexity, larger tumors, and tumor grades 3-4 were found to be predictors of preoperatively detectable ctDNA status. CONCLUSION Preoperative ctDNA was detectable in 61% of patients with nonmetastatic RCC, and it correlated with clinically relevant features. Clinical trials should consider incorporating both preoperative and postoperative ctDNA analyses to augment prediction of disease recurrence and to refine treatment decision making.