Dr Tan on the Potential Utility of ctDNA in RCC

Alan Tan, MD, assistant professor, Department of Internal Medicine, director, Genitourinary (GU) Medical Oncology, Rush University, Rush Medical College, discusses the ongoing investigation and potential utility of circulating tumor DNA (ctDNA) in patients with renal cell carcinoma (RCC).

In recent years, ctDNA has started to establish significance in specific cancer histologies, Tan begins. The journey began with colorectal cancer, utilizing molecular residual disease identification to assess the risk of metastatic recurrence, forming the foundation for recommending adjuvant chemotherapy or immunotherapy for individual patients, he explains. In the realm of genitourinary oncology, preliminary yet compelling evidence has emerged in bladder cancer, he notes, highlighting that through ctDNA, there is potential to stratify patients at the highest risk of metastatic recurrence, offering a prospect for tailored adjuvant chemotherapy. Several ongoing clinical trials have looked at identifying patients requiring treatment or those who could be considered for de-escalation based on ctDNA status, Tan notes.

The landscape becomes intricate in kidney cancer, primarily due to its classification as a low-shedding tumor, creating doubts regarding the readiness of ctDNA for clinical use in selecting patients at the highest risk of recurrence, owing to perceived inadequacies in the sensitivity of current commercial tests, Tan states. However, the field is evolving, embracing more sensitive testing, deeper sequencing, and alternative technologies such as methylation to unravel the complexities, he continues.

Looking forward, the potential utility of ctDNA appears promising in renal cell carcinoma, particularly in the metastatic setting, he continues. Patients with metastatic disease typically present with higher tumor volumes and a notable shedding of ctDNA, particularly in organs such as the bones or the liver. A proposed investigator-initiated trial aims to longitudinally track ctDNA to measure its correlation with disease progression, Tan says. The objective is to discern patterns of ctDNA clearance, offering insights into molecular-level disease detection. This strategy holds the promise of facilitating de-escalation decisions, particularly in the context of toxic treatments such as TKIs, he emphasizes. Recent studies, while lacking a specific biomarker, prompt a compelling suggestion to employ ctDNA clearance as a reliable metric for molecular-level disease detection. This approach could potentially guide treatment decisions, allowing timely responses to early biochemical recurrence, Tan concludes.