The Emerging Role of Stereotactic Ablative Radiotherapy for Primary Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Context: Stereotactic ablative radiotherapy (SABR) is an emerging treatment option for primary renal cell carcinoma (RCC). Objective: To systematically review the literature on SABR for primary RCC and perform a meta-analysis evaluating local control (LC), toxicity, and renal function. Evidence acquisition: A PROSPERO-registered (#115573), Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA)-based systematic review of the literature was conducted (1995–2019). Studies of SABR targeting primary RCC tumors were included, while those targeting only metastases were excluded. The primary outcome was LC defined as tumor size reduction and/or absence of local progression. Secondary outcomes included toxicity (Common Terminology Criteria for Adverse Events) and renal function (change in estimated glomerular filtration rate [eGFR]). Weighted random-effect meta-analyses using the DerSimonian and Laird method were conducted for primary and secondary outcomes. The I² statistic and Cochran's Q test were used to assess heterogeneity. Evidence synthesis: From 2386 PubMed entries and 924 meeting abstracts, 26 studies were identified (11 prospective trials), including 383 tumors in 372 patients, most of whom were deemed inoperable. Weighted averages (ranges) of median follow-up, median age, and mean tumor size were 28.0 (5.8–79.2) mo, 70.4 (62–83) yr, and 4.6 (2.3–9.5) cm, respectively. RCC histology was confirmed in 78.9% of patients who underwent pretreatment biopsy. Dose fractionation varied, but 26 Gy in one fraction and 40 Gy in five fractions were most common. The random-effect estimates for LC, grade 3–4 toxicity, and post-SABR eGFR change were 97.2% (95% confidence interval [CI]: 93.9–99.5%, I² = 20%), 1.5% (95% CI: 0–4.3%, I² = 0%), and –7.7 ml/min (95% CI: –12.5 to –2.8, I² = 2%), respectively, and heterogeneity was minimal. Six patients with pre-existing renal dysfunction (2.9%) required dialysis. Conclusions: Renal SABR is locally effective and associated with low toxicity rates for primary RCC, despite treatment of larger tumors in older, mostly medically inoperable patients. Patient summary: Stereotactic ablative radiotherapy is a high-precision, noninvasive radiation treatment requiring few outpatient visits, and represents a safe and effective management option for primary renal cell carcinoma. Stereotactic ablative radiotherapy (SABR) achieves excellent local control, minimal toxicity, and acceptable renal function impact despite larger primary RCCs in older, mostly inoperable patients. This non-invasive, outpatient treatment may represent an alternative for selected patients with primary RCC.