Longitudinal Testing of Circulating Tumor DNA in Patients With Metastatic Renal Cell Carcinoma.

Purpose: Tumor-informed circulating tumor DNA (ctDNA) has shown promise as a biomarker for treatment response monitoring (TRM) in a variety of tumor types, with the potential to improve clinical outcomes. We evaluated ctDNA status and dynamics during surveillance and as part of TRM with clinical outcomes in both patients with clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC) treated with standard-of-care immunotherapy or targeted therapy regimens.

Methods: This was a multicenter retrospective analysis of real-world data obtained from commercial ctDNA testing (Signatera, Natera, Inc) in patients with metastatic RCC. Clinical data were collected on International Metastatic RCC Database Consortium (IMDC) risk category, pathologic subtype, and grade.

Results: The cohort comprised 92 patients (490 plasma samples) including both clear cell and non-clear cell histological subtypes (ccRCC: 79.3%; nccRCC: 14.1%; unclassified: 6.5%). Most of the patients belonged to the IMDC intermediate-risk category (75%, 69/92). Median follow-up was 10 months (range, 4.2-25.8). ctDNA dynamics were assessed in 56 patients on treatment, and ctDNA status was analyzed in the surveillance cohort (n = 32 patients). Serial ctDNA negativity or clearance correlated with improved progression-free survival (PFS) compared with those who became or were persistently ctDNA positive on therapy (hazard ratio [HR], 3.2; = .012). In the surveillance cohort, patients with positive ctDNA longitudinally experienced significantly inferior PFS (HR, 18; = .00026) compared with those who were serially negative.

Conclusion: Collectively, we show that serial ctDNA monitoring provides prognostic information for patients undergoing treatment or surveillance, and our findings demonstrate high concordance between ctDNA status/dynamics and subsequent clinical outcomes.