132 - Long-Term Outcomes from a Phase 2 Trial of Stereotactic Ablative Radiotherapy (SAbR) for Primary Renal Cell Carcinoma

Purpose/Objective(s): The first prospective phase 2 trial investigating stereotactic ablative radiotherapy (SAbR) for primary renal cell carcinoma (RCC) demonstrated excellent 1-year local control and acceptable renal function decline¹. We now report the long-term (>6 years) treatment outcomes and adverse events of this study.

Materials/Methods: Sixteen patients (median age 72 years [IQR 65-80]; 11 male, 5 female; 9 white, 6 black, 1 Hispanic) with biopsy-proven, enlarging primary RCC (=5 cm) were treated with SAbR (36 Gy in 3 fractions, n=10 or 40 Gy in 5 fractions, n=6). Median follow-up was calculated from SAbR start to last documented contact. Local control (LC) and best treatment response were evaluated per RECIST 1.1. Disease control was assessed at last follow-up with imaging (progression vs no progression).Renal function was assessed by eGFR, calculated using the CKD-EPI formula incorporating age, gender, race, and serum creatinine. eGFR change was defined as follow-up minus baseline eGFR. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method using progression/death as event and censoring at last follow-up. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Results: Median follow-up was 77.6 months (IQR 43.9–97.4), which to our knowledge represents the longest reported median follow-up for SAbR in primary RCC. At last follow-up, LC per RECIST 1.1 was 15/16 (93.8%). Best response was partial response (PR) in 6/16 (37.5%) and stable disease (SD) in 10/16 (62.5%) patients. All PR occurred in patients treated with 3-fraction SAbR whereas no PR occurred in the 5-fraction cohort. Disease control rate was 15/16 (93.8%). No new local failures or progression events occurred beyond previously documented events¹, suggesting late in-field failure after SAbR is rare. Survival status at last follow-up was 10/16 alive (62.5%) and 6/16 deceased (37.5%). Estimated 5-year PFS was 91.7% and 5-year OS was 69.1%. Median eGFR declined from 56.7 mL/min/1.73m² at baseline to 49.9 at ~12 months (median ? -7, IQR -16.8 to -6.5), then to a median of 47.6 at last follow-up (median ? -7.9, IQR -12.2 to -2.7), suggesting stabilization of renal function in the chronic phase without continued progressive decline beyond the first year. No patients required dialysis. SAbR remained well tolerated, with no late grade =2 adverse events observed.

Conclusion: With over 6.5 years median follow-up, this first phase 2 trial of SAbR for primary RCC demonstrates durable disease control, sustained high LC, favorable long-term survival, and reassuring long-term renal safety. The absence of new late failures and lack of significant late toxicity further support SAbR as a definitive, noninvasive treatment option for appropriately selected patients with primary RCC.