Metastasis-Directed Radiotherapy Shows Promise for Oligometastatic RCC

In a significant advancement for oncological treatment, a phase 2 trial conducted at the University of Texas MD Anderson Cancer Center has demonstrated that metastasis-directed radiotherapy (MDRT) without concurrent systemic therapy offers durable disease control in patients with oligometastatic clear cell renal cell carcinoma (RCC). The findings were presented at the 2025 Kidney Cancer Research Summit held on July 17, 2025, in Boston, Massachusetts.

The trial, registered under NCT03575611, involved patients exhibiting oligometastatic RCC with up to five metastases and no prior systemic therapy or a gap of over one month from any previous systemic treatment. Participants received stereotactic radiation therapy alongside standard imaging and biopsy procedures, followed by routine monitoring. The trial reported a median progression-free survival (PFS) of 34.0 months and a median systemic therapy-free survival (STFS) of 17.7 months, as well as a three-year overall survival (OS) rate of 86.5%.

Dr. Chad Tang, MD, an associate professor in the departments of Radiation Oncology, Translational Molecular Pathology, and Investigational Cancer Therapeutics at the University of Texas MD Anderson, emphasized the advantages of this approach, stating, "Metastasis-directed therapy without systemic therapy offers advantages in costs, toxicities, and clinic visits over frontline systemic therapies." This assertion is based on the observation that costs associated with immunotherapy and tyrosine kinase inhibitors (TKIs) range from $150,000 to $300,000 annually, whereas stereotactic body radiation therapy costs approximately $15,000 to $40,000 per round.

The trial's findings also highlighted the safety profile of MDRT. Of the 78 participants, 20.8% experienced grade 2 or higher adverse events, while only 6.7% faced grade 3 or higher adverse events. Notably, grade 3 toxicities were reported in just one patient. The most prevalent grade 2 adverse events included musculoskeletal pain and pneumonitis, while the common grade 3 events were predominantly musculoskeletal pain and leukocytosis.

This trial builds upon prior research indicating the potential of active surveillance in metastatic renal cell carcinoma. According to a study published in the *Lancet Oncology* in 2016, surveillance strategies have shown promise in managing metastatic RCC, paving the way for further investigations into personalized approaches to treatment.

The study's investigators noted that 60% of patients were minimal residual disease (MRD)-positive at baseline, with a median tumor fraction of 22.5 ppm. Encouragingly, 25% of these MRD-positive patients converted to MRD-negative status after three months of treatment. Improved STFS was observed in MRD-negative patients compared to MRD-positive patients, indicating the need for biomarkers to guide treatment decisions.

With the increasing complexity of cancer treatments, the role of biomarkers, particularly circulating tumor DNA (ctDNA), is becoming critical. Dr. Tang pointed out, "Biomarkers are needed at baseline to select patients and after metastasis-directed therapy to guide surveillance versus systemic therapy. Circulating tumor DNA via a second-generation assay has the potential to inform both roles."

This phase 2 trial represents a pivotal step toward optimizing treatment protocols for oligometastatic RCC, offering hope for a more effective and less toxic management strategy. The implications for clinical practice could be substantial, particularly as the medical community continues to seek innovative approaches to enhance patient outcomes while minimizing treatment burdens. Future studies will be essential to validate these findings and further elucidate the potential of MDRT in broader oncological contexts.