Enhancing outcomes in metastatic renal cell carcinoma: Integrating precision radiotherapy with targeted therapy and anti-PD-1 immunotherapy.

PURPOSE: This study assesses the safety and disease control outcomes in metastatic renal cell carcinoma (mRCC) patients undergoing concurrent tyrosine kinase inhibitors (TKI), immune checkpoint inhibitors (ICIs), and high-dose stereotactic ablative body radiotherapy (SABR) .

PATIENTS AND

METHODS

Between February 2020 to May 2023, 54 mRCC patients receiving vascular endothelial growth factor (VEGF) targeted therapy and ICIs with high-dose radiotherapy (RT) were included. Genetic testing was performed on 25 pathology samples using the Acornmed 70™ panel. Endpoints included progression-free survival (PFS) 1, PFS2 (time to progression to change systemic therapy), LRFS, OS, disease control rate (DCR) and safety. Kaplan‒Meier analysis was used for time-to-event endpoints. HRs and 95% CIs were calculated. R version 4.3.1 was used for statistical analysis

RESULTS

In this study involving 54 patients, SABR was employed in 81% of cases, achieving a 98% DCR. Median PFS1 was 16.9 months, with 2-year PFS2 and OS rates of 53% and 81%, respectively. Subgroup analysis revealed that early RT significantly improved PFS1 (P = 0.023). VHL-driven mRCC demonstrated a trend toward improved PFS1, statistical significance was not reached due to the limited sample size (P = 0.3). Safety analysis indicated grade 3 or 4 treatment-related adverse events in 50% of patients, with no grade 5 events.

CONCLUSIONS

The investigated trimodality treatment strategy is both safe and effective, resulting in prolonged PFS without requiring a change in systemic treatment. Overall, early RT intervention may offer additional benefits. Future research should provide molecular-level insights into treatment response.