Metastasis-Directed Radiotherapy Shows Improved Kidney Cancer Outcomes

Metastasis-directed radiotherapy alone showed encouraging results, including favorable survival rates and low side effects, for patients with oligometastatic clear cell renal cell carcinoma, a specific type of kidney cancer, according to a phase 2 trial presented at the 2025 Kidney Cancer Research Summit.

With a median follow-up of 36.3 months, median progression-free survival was 34 months; median systemic therapy-free survival was 17.7 months; and 3-year overall survival was 86.5%.

Investigators noted that surveillance was associated with a median systemic therapy-free survival of 14.9 months in a phase 2 trial published in Lancet Oncology.

At baseline, 60% of patients (47 of 78) were minimal residual disease positive; among these, the median tumor fraction was 22.5 ppm. After 3 months, 25% of initially minimal residual disease-positive patients converted to negative.

Patients who were minimal residual disease negative showed improved systemic therapy-free survival compared with those who were positive since enrollment and since the 3-month assessment.

“Metastasis-directed therapy without systemic therapy offers advantages in costs, side effects, and clinic visits over frontline systemic therapies,” wrote study author Dr. Chad Tang, associate professor at the University of Texas MD Anderson Cancer Center, and coauthors. “[Metastasis-directed therapy] without systemic therapy showed favorable overall survival and side effect profiles. Biomarkers are needed at baseline to select patients and after therapy to guide surveillance versus systemic treatment. Circulating tumor DNA using a second-generation assay may help inform both roles.”

The trial enrolled patients with oligometastatic renal cell carcinoma with clear cell histology, up to five metastases, and no prior systemic therapy or more than one month off prior systemic therapy. Treatment included standard imaging and biopsy, blood draw, stereotactic radiation with or without local surgery to all disease sites, followed by imaging and blood draw. If progression occurred, the cycle restarted; otherwise, systemic therapy began.

Co-primary endpoints were progression-free survival per RECIST 1.1 and systemic therapy-free survival, defined as median systemic therapy-free survival greater than 25 months.

Immunotherapy alone or in combination and tyrosine kinase inhibitors cost approximately $150,000 to $300,000 annually, while stereotactic body radiation therapy costs about $15,000 to $40,000 per round; grade 3 or higher side effects occur in 45% to 85% and 5% to 10%, respectively; clinic visits occur at least monthly and one to two visits per radiation round.

Regarding safety, grade 2 or higher side effects were seen in 20.8% of patients, grade 3 or higher side effects in 6.7%, and grade 3 side effects in only one patient. Most common grade 2 side effects included musculoskeletal pain (10 patients), pneumonitis (five patients), cough (three patients), and shortness of breath (two patients). Most common grade 3 side effects were musculoskeletal pain (five patients), increased white blood cells (two patients), pleural effusion (one patient), and abdominal distension (one patient). The only grade 4 side effect was high blood sugar (one patient).

References

• “Phase 2 trial of metastasis directed radiotherapy without systemic therapy (MRWS) for oligometastatic clear cell renal cell carcinoma (ccRCC) and investigation of circulating tumor DNA (ctDNA) as a personalized biomarker,” by Dr. Chad Tang. Presented at the 2025 Kidney Cancer Research Summit; July 17, 2025; Boston, MA.
• “Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2 trial,” by Dr. Brian I. Rini. Lancet Oncology.

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