Utility of circulating tumor DNA in management of diverse renal malignancies: Insights from a case series in adjuvant and recurrent/metastatic settings.

BACKGROUND

Circulating tumor DNA (ctDNA) monitoring offers a minimally invasive method for detecting molecular residual disease and assessing treatment response. While increasingly adopted in several cancers, its clinical utility in renal malignancies remains underexplored, primarily due to low ctDNA shedding in kidney cancers.

METHODS

We present a case series of six patients with diverse renal malignancies (clear cell renal cell carcinoma [ccRCC], papillary RCC, translocation RCC, malignant angiomyolipoma, and squamous cell carcinoma of the renal pelvis) managed in both adjuvant and recurrent/metastatic settings. All patients underwent serial ctDNA testing using the Signatera (exome-based) tumor-informed assay alongside conventional imaging.

FINDINGS: ctDNA results influenced clinical decisions in all six cases. In the adjuvant setting, positive ctDNA indicated molecular residual disease, prompted initiation of therapy, and allowed monitoring of treatment response and recurrence during surveillance. In recurrent/metastatic disease, ctDNA trends often preceded radiographic progression, enabling earlier intervention or treatment modification. In some instances, ctDNA provided crucial insights during imaging uncertainty or treatment breaks due to toxicity. Sustained ctDNA clearance was associated with favorable cancer-specific outcomes.

CONCLUSIONS

While the lower sensitivity, limited negative predictive value, and financial burden of ctDNA monitoring in kidney cancers constitute significant limitations, a positive result can potentially serve as a highly informative adjunct to imaging-based surveillance for monitoring disease status and treatment response. This case series supports and informs future studies on ctDNA in the management of renal malignancies.

FUNDING: ctDNA testing for these patients was supported by Natera, the manufacturer of the Signatera assay.