Stereotactic Body Radiotherapy for Large Primary Renal Cell Carcinoma: A Report from the International Radiosurgery Oncology Consortium for Kidney (IROCK)

Abstract

Thermal ablation is an established option for small renal cell carcinomas (RCC). However, patients with larger (T1b, >4cm) RCC not suitable for surgery have few treatment options as thermal ablation is less effective in this setting. We hypothesize that SBRT has similar local efficacy (>90%) in larger RCC to that of small RCC. Individual patient data from nine IROCK institutions in Germany, Australia, USA, Canada, and Japan were pooled. Outcomes from larger RCC were compared to small RCC. Patients with metastatic disease or urothelial histology were excluded from the database (n=31). Demographics, treatment, oncologic and renal function outcomes were compared between cohorts using the Chi-square test, Fisher’s exact test, two-sample T-test, or Wilcoxon rank sum test as appropriate. Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards regression were generated for oncologic outcomes. There were 95 patients with larger RCC identified from 192 eligible patients. Median follow up was 2.5 years. Median tumor size in the larger RCC group was 4.9 cm compared to 2.9 cm in the small RCC group. In the overall cohort, normal renal function (eGFR>90mL/min) at baseline was recorded in 9.0% of patients, with 26% having moderate to severe dysfunction (eGFR <45mL/min). Patients with large RCC were of poorer performance status (ECOG 0-1 in 81.1% vs. 93.8%, p = 0.008) and were older (mean age: 75 years vs. 69 years, p < 0.001). Toxicities ≥ grade 2 occurred in 12 patients (6.3%) with no differences in toxicity rates between cohorts (p = 0.526). Median baseline eGFR was lower in the larger RCC cohort (59.0mL/min vs. 68.5 mL/min, p = 0.013), and demonstrated a median reduction post-SBRT of -5.8 v mL/min versus -2.9 mL/min, p = 0.073). There were 8 recurrences (8.4%) in larger RCCs, compared to 1 recurrence (1.0%) in the small RCC cohort. Local control at 1-year was 100% in both cohorts, and at 3-years was similar at 96.6% vs. 98.5%, respectively (log-rank p = 0.512). Distant control was worse in larger RCC at 1- and 3-years, at 97.8% vs. 100% and 87.0% vs. 100% respectively (log-rank p = 0.006). Cancer-specific survival (CSS) at 3-years was 91.4% versus 96.2% (log-rank p = 0.224). Overall survival (OS) at 3-years was 72.3% vs. 84.6% (log-rank p = 0.294). On multivariable analysis, higher pre-SABR creatinine (hazard ratio [HR] per 10 μmol/L: 1.08, p = 0.002) and poor performance status (HR: 3.85, p = 0.004) were associated with inferior OS. Increasing tumor size (HR per 1 cm: 1.18, p = 0.028) was associated with inferior CSS. SBRT for larger RCC appears tolerable and similarly locally effective as in small RCC, although associated with a higher likelihood of metastatic progression and death. Efforts to reduce risk of distant recurrence, such as adjuvant systemic therapy, should be further investigated.