Long-Term Outcomes of SABR to Primary Renal Cell Carcinoma: A Multicenter Analysis from IROCK (International Radiosurgery Oncology Consortium for Kidney)

Abstract

<h3>Purpose/Objective(s)</h3> Patients with renal cell carcinoma (RCC) not suitable for surgery have few curative treatment options, particularly as thermal ablation has diminishing efficacy in RCC > 3 cm or adjacent to collecting system. Stereotactic ablative body radiotherapy (SABR) is a novel option limited by lack of long-term outcome data. We hypothesize that SABR represents an effective and safe, nephron-sparing alternative for RCC in the long-term. <h3>Materials/Methods</h3> Individual patient data from 12 institutions from IROCK were pooled. Patients with M1 disease and/or upper tract urothelial carcinoma were excluded. Minimum eligible follow-up was ≥ 2 years. Demographics, treatment, oncologic and renal function outcomes were assessed using descriptive statistics. Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards regression were generated for oncologic outcomes. Local failure was investigator defined using RECIST 1.1. Patterns of failure were described using a cumulative incidence function with death as competing event. Toxicity was described using CTCAE v4.0. <h3>Results</h3> In 190 patients, the median follow-up was 5.0 years (range?). The mean ± SD tumor diameter was 4.2 ± 2.2 cm and 95 patients (50%) had ≥ T1b (≥ 4 cm) primaries. Median age was 74 years (interquartile range [IQR]: 66-82), 73.2% were male and 87.6% had good performance status (ECOG 0-1 or KPS ≥ 70%). In patients for whom operability details were reported, 75.0% were defined as inoperable by the referring urologist, mostly for cardiovascular comorbidities (46.9%). Baseline tumor complexity was moderate (median RENAL [1] score of 7 [IQR: 5-9]), and 56 patients (29.5%) had a solitary kidney. Mean ± SD BED₁₀ delivered was 88.3 ± 24.7 Gy. Mean ± SD baseline estimated glomerular filtration rate (eGFR) was 58.9 ± 22.6 mL/min (mild-to-moderate dysfunction) with 53 patients (28.0%) of the cohort having moderate-to-severe dysfunction (eGFR < 45 mL/min). At 3- and 5-years following SABR, mean ± SD eGFR decreased by -10.8 ± 16.6 mL/min and -13.5 ± 14.9 mL/min, respectively. Nine patients (4.7%) required dialysis. Seventy patients (36.8%) had a grade 1-2 toxicity, and one patient (0.5%) had a grade 4 toxicity (gastrointestinal). Cancer-specific survival (CSS) and progression-free survival (PFS) at 3 years were 95.5% and 72.1%, and at 5 years were 92.0% and 63.6%, respectively. Local, distant and any failure at 5 years were 5.5%, 10.8% and 13.0%. On multivariable analysis, increasing tumor size was associated with inferior CSS (HR per 1 cm increase: 1.41; 95% CI: 1.15-1.71; <i>p</i> < 0.001), PFS (HR: 1.10; 95% CI: 1.01-1.19; <i>p</i>=0.030), and any failure (HR: 1.20; 95% CI: 1.10-1.32; <i>p</i> < 0.001). <h3>Conclusion</h3> At 5-years post-therapy, SABR for primary RCC was associated with excellent local efficacy and good oncological outcomes, with only modest impact on renal function. [1] A. Kutikov & R.G. Uzzo "The RENAL nephrometry score: a comprehensive standardized system for quantitating renal tumor size, location and depth." J. Urol (2009)182(3):844