Multimodal Treatments for Brain Metastases from Renal Cell Carcinoma: Results of a Multicentric Retrospective Study

SIMPLE SUMMARY: Around 2–15% of primary renal cell carcinoma patients (RCC) will develop brain metastases (BMs) during the disease course. The prognosis of brain metastatic RCC patients is poor when compared with extracranial metastatic patients, and determining the optimal local therapeutic approach is a challenge. The aim of our retrospective multi-institutional study was to assess the efficacy of local treatments, radiosurgery in single or multiple fractions (SRS/HSRS) with or without surgery, and to identify prognostic factors eventually conditioning outcome. Patients with limited BMs (up to four) were treated with single-dose SRS in cases of small lesions, HSRS for large BMs unsuitable for surgical resection, or surgical resection followed by SRS/HSRS. We confirmed the efficacy and safety of SRS/HSRS in 120 patients analyzed for 136 BMs treated. Patients with favorable/intermediate International Metastatic Database Consortium (IMDC) score, with a higher RCC-graded prognostic assessment (GPA) score, with an early occurrence of BMs from primary diagnosis, with absence of extracranial metastases, and who underwent a combined local treatment (surgery plus adjuvant HSRS) had a better outcome. ABSTRACT: The aim of this study was to evaluate the clinical outcomes of a large series of brain metastatic renal cell carcinoma (BMRCC) patients treated in three Italian centers. Methods: A total of 120 BMRCC patients with a total of 176 lesions treated were evaluated. Patients received surgery plus postoperative HSRS, single-fraction SRS, or hypofractionated SRS (HSRS). Local control (LC), brain distant failure (BDF), overall survival (OS), toxicities, and prognostic factors were assessed. Results: The median follow-up time was 77 months (range 16–235 months). Surgery plus HSRS was performed in 23 (19.2%) cases, along with SRS in 82 (68.3%) and HSRS in 15 (12.5%). Seventy-seven (64.2%) patients received systemic therapy. The main total dose and fractionation used were 20–24 Gy in single fraction or 32–30 Gy in 4–5 daily fractions. Median LC time and 6 month and 1, 2 and 3 year LC rates were nr, 100%, 95.7% ± 1.8%, 93.4% ± 2.4%, and 93.4% ± 2.4%. Median BDF time and 6 month and 1, 2 and 3 year BDF rates were n.r., 11.9% ± 3.1%, 25.1% ± 4.5%, 38.7% ± 5.5%, and 44.4% ± 6.3%, respectively. Median OS time and 6 month and 1, 2 and 3 year OS rates were 16 months (95% CI: 12–22), 80% ± 3.6%, 58.3% ± 4.5%, 30.9% ± 4.3%, and 16.9% ± 3.6, respectively. No severe neurological toxicities occurred. Patients with a favorable/intermediate IMDC score, a higher RCC-GPA score, an early occurrence of BMs from primary diagnosis, absence of EC metastases, and a combined local treatment (surgery plus adjuvant HSRS) had a better outcome. Conclusions: SRS/HSRS is proven to be an effective local treatment for BMRCC. A careful evaluation of prognostic factors is a valid step to manage the optimal therapeutic strategy for BMRCC patients.