Stereotactic Body Radiation Therapy for Primary Renal Cancer and Genetic Markers of Response: A Phase 2 Trial

Controlled outcome assessment of radiotherapy for primary renal cell carcinoma (RCC) remains limited, particularly regarding its impact on ipsilateral renal function and predictors of response. We evaluated oncological and renal function outcomes of stereotactic body radiation therapy (SBRT) for RCC and identified genomic predictors of response. Our study cohort comprised 83 surgically unfit patients with cT1a RCC who were prospectively enrolled to receive SBRT of 42 Gy in three fractions between 2016 and 2022. The median tumor size was 2.3 cm and local control was achieved in 78 patients, including eight with a complete response. The 3-yr survival rates were 96% (95% confidence interval [CI] 89.8-99.9) for progression-free survival and 96% (95% CI 89.4-99.9%) for cancer-specific survival. The glomerular filtration rate of the treated kidney decreased up to 12-18 mo (-9.8 ml/min/1.73 m²) but stabilized thereafter. Transcriptome sequencing conducted on biopsy specimens from five responders and eight nonresponders showed enrichment of apical surface/junction pathways among responders, and enrichment of cell cycle, DNA repair, oxidative phosphorylation, and hypoxia pathways among nonresponders. A machine learning model based on gene expression demonstrated good predictive performance, with a cross-validated area under the receiver operating characteristic curve of 0.9. SBRT for T1a RCC was acceptable in terms of intermediate-term cancer control and preservation of renal function. Distinctive genomic profiles may aid in identifying optimal candidates pending external validation.