Stereotactic Radiation Therapy for Renal Cell Carcinoma Metastases: A Meta-Analysis of 28 Studies

Abstract

Utilization of stereotactic radiotherapy in the management of renal cell carcinoma is increasing internationally (Siva et al, Nat Rev Urol, 2017). Our objectives are to assess the efficacy and safety of stereotactic radiotherapy for metastatic renal cell carcinoma (RCC). We hypothesized that local control is >85% and significant toxicity is <15%. A PICOS/PRISMA/MOOSE selection protocol was utilized to select studies published between 1998 and 2019. The primary outcome was 1-year local control (LC) and 1-year overall survival (OS); secondary outcome was incidence of any acute or late Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 toxicity. Each outcome was stratified by extra- or intracranial RCC involvement. Weighted random effects meta-analyses were conducted, where the DerSimonian and Laird method was used to calculate between study variance for each of the primary and secondary outcomes. Heterogeneity was assessed using the I2 statistic and Cochran’s Q-Test. Publication bias was assessed using funnel plots and the Egger Test, where publication bias was considered absent if the p-value was < 0.05. A total of 265 studies were initially screened. A total of 28 studies (27 retrospective, 1 prospective) from 8 countries, were included in the meta-analysis. There were a total of 1,602 mutually exclusive patients (679 extracranial/923 intracranial) and 3,892 lesions (1,159 extracranial/2,733 intracranial). The median patient age was 62 years (range: 55-56 years). The median treatment volume was 59.7 cc for extracranial lesions (interquartile range: 31.1 - 71.4) and 2.3 cc for intracranial lesions (interquartile range: 1.3 – 4.3). Under the random effects model, the summary effect size for 1-year LC was 89.1% (95% confidence interval [CI]: 83.6%-93.7%, I2=71%) and 90.1% (95% CI: 83.5%-95.3%, I2=74%) for extracranial and intracranial disease, respectively. For 1-year OS: 86.8% (95% CI: 62%-99.8%, I2=95%) and 49.7% (95% CI: 41.1%-58.3%, I2=74%) for extracranial and intracranial disease, respectively. The incidence of any grade 3-4 toxicity was 0.7% (95% CI: 0%-2.1%, I2=0%) and 1.1% (95% CI: 0%-7.4%, I2=53%) for extracranial and intracranial disease, respectively. There was no publication bias present for any of the outcomes (Egger Test: p>0.05), regardless of site. Stereotactic radiotherapy is safe and efficacious in the management of extracranial and intracranial RCC oligometastases, with LC at 90% and any significant toxicity at 1%. Patients with intracranial metastases have worse survival than those with extracranial disease, despite smaller treatment volumes. Further prospective studies are needed.