Dr Tang on the Implementation of Metastasis-Directed Radiotherapy in Oligometastatic ccRCC

"We recognize that one of the key problems with implementing this treatment strategy worldwide is that radiolographic findings are imperfect. What we need are quantifiable, reproducible metrics that can be used to stratify patients. With this assay, ctDNA was able to be a prognostic marker that we can refine further to be able to [improve selection]."

Chad Tang, MD, an associate professor in the Department of Radiation Oncology of the Division of Radiation Oncology; in the Department of Translational Molecular Pathology; and in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, discussed the feasibility of incorporating metastasis-directed radiotherapy without systemic therapy into clinical practice for patients with oligometastatic clear cell renal cell carcinoma (ccRCC).

Tang and colleagues designed a phase 2 trial (NCT03575611) to evaluate whether patients with oligometastatic ccRCC who received stereotactic radiation with or without surgical local therapy could achieve a median systemic therapy–free survival of at least 24 months.

Among patients enrolled in the study (n = 121), the median systemic therapy–free survival was 34 months (95% CI, 28-54). Importantly, the lower bound of the 95% confidence interval exceeded the trial’s predefined benchmark of 24 months, Tang noted. The median progression-free survival was 18 months (95% CI, 15-22), and the median overall survival (OS) was not reached, with a 3-year OS rate of 87%, he reported. Local therapy was not associated with a higher rate of grade 3 or higher toxicities compared with expectations with systemic therapy, Tang added.

One barrier to broad implementation of this strategy is the variability in radiographic interpretation, particularly in quantifying metastatic burden, Tang explained. Differences in imaging modalities and reader assessments can result in inconsistent classification of oligometastatic disease, according to Tang. To address this, the study explored the utility of circulating tumor DNA (ctDNA) as a reproducible, quantifiable biomarker. Baseline and follow-up ctDNA levels demonstrated prognostic relevance for systemic therapy–free survival and may help stratify patients more accurately in future applications, Tang said. He emphasized that refining ctDNA metrics could support broader integration of this non-systemic approach into clinical decision-making.