133 - Efficacy and Safety of Targeted-Immunotherapy with or without Stereotactic Ablative Radiotherapy for Recurrent/Metastatic Renal Cell Carcinoma: The Result of a Multicenter Ambidirectional cohort study

Purpose/Objective(s):

This study aimed to evaluate the clinical efficacy and safety of combining Stereotactic Ablative Radiotherapy (SABR) with targeted-immunotherapy in patients with recurrent/metastatic renal cell carcinoma (RCC).

Materials/Methods:

We conducted a multi-center, bidirectional cohort study comparing targeted-immunotherapy alone (Control Group, N=200) with targeted-immunotherapy combined with SABR (Experimental Group, N=100). The primary endpoint was Progression-Free Survival 2 (PFS2), defined as the time from the initiation of targeted-immunotherapy until a necessary change in systemic therapy due to subsequent disease progression. Secondary endpoints included Progression-Free Survival 1 (PFS1), defined as the time from the initiation of targeted-immunotherapy until the first time of disease progression, Overall Survival (OS), Distant Metastasis-Free Survival (DMFS), and Primary Progression-Free Survival (PPFS). Propensity Score Matching (PSM) was utilized to balance baseline covariates.

Results: With a median follow-up duration of 21.4 months, the targeted-immunotherapy with SABR approach demonstrated superior clinical outcomes across multiple survival metrics. In the PSM-matched cohort (N=248), the addition of SABR significantly prolonged the duration of current systemic therapy, with a median PFS2 of 47.7 months in the experimental group compared to 28.9 months in the control group (p < 0.001). This sustained disease control translated into a substantial overall survival (OS) benefit (p = 0.001). SABR achieved an exceptional local control rate (LCR) of 98.9% at 5 years. The Primary Progression-Free Survival (PPFS), where the experimental group reached a median of 60.1 months, vastly outperforming the control group's 23.8 months (p < 0.001). However, the Distant Metastasis-Free Survival (DMFS) showed no statistically significant difference between the two groups after matching (35.7 months vs. 33.1 months, p = 0.120). Patients receiving radiotherapy before first-line systemic therapy failure (early intervention) achieved significantly longer PFS1 (30.1 vs. 15.9 months, p < 0.001). Genomic investigations highlighted that VHL mutations (60%) were the most prevalent, with patients harboring isolated VHL mutations exhibiting a trend toward superior PFS1. The incidence of Grade 3–4 adverse events was comparable between the experimental (39.0%) and control (40.5%) groups.

Conclusion:

The integration of SABR with targeted and immunotherapy represents a highly effective paradigm for the management of recurrent/metastatic RCC, significantly extending the efficacy of systemic treatments and improving long-term survival. While SABR does not appear to significantly alter the DMFS, its ability to secure local disease control makes it an indispensable component of multi-modal therapy. Early clinical intervention, particularly for patients with VHL-driven genomic profiles, should be prioritized.