Radiotherapy Strategies in Metastatic Clear Cell Renal Cell Carcinoma

Michael Serzan, MD Dana-Farber Cancer Institute | Shreyas Kalantri, MD University of Louisville

Key Points

• The CYTOSHRINK trial evaluated whether the addition of stereotactic body radiation therapy (SBRT) to the primary kidney tumor could enhance immunotherapy responses in patients with metastatic clear cell renal cell carcinoma (RCC).

• Although the trial did not improve progression-free survival (PFS), the regimen was feasible and did not increase toxicity.

• Biomarkers like kidney injury molecule-1 (KIM-1) may help guide future treatment decisions.

During a discussion at the 2026 ASCO Genitourinary Cancers Symposium (ASCO GU 2026), Shreyas Kalantri, MD, of the University of Louisville, and Michael Serzan, MD, of Dana-Farber Cancer Institute, reviewed the evolving role of radiotherapy in combination with systemic immunotherapy in metastatic RCC.

The CYTOSHRINK trial, which was presented at ASCO GU 2026, evaluated whether targeting the primary kidney tumor with SBRT could enhance the immune response generated by checkpoint inhibitor therapy (ipilimumab and nivolumab). Patients with first-line metastatic clear cell RCC received nivolumab plus ipilimumab. They were randomized to receive SBRT to the primary tumor between the first and second cycles of immunotherapy or to continue systemic therapy alone. 

However, the study did not meet its primary end point of PFS, and no significant improvement in long-term outcomes with the addition of SBRT were observed.

Dr. Serzan emphasized that the regimen was well tolerated, and there was no increase in treatment-related toxicity.

He called for more prospective trials and biomarker strategies, such as those evaluating KIM-1, to help identify patients who may be the best candidates for these types of therapies.