Surgery vs. Radiosurgery for Patients with Localized Metastatic Brain Disease: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

SIMPLE SUMMARY: With an incidence of 14 cases per 100,000 people per year, brain metastases (BMs) are the most frequent malignant intracranial lesions, occurring in up to 40% of all patients with solid tumors. Median survival with the best standard of care is between 8 and 16 months, but subcohorts of patients achieved longer survival rates. These subcohorts include patients with good performance status and single (or very few) BMs eligible for aggressive treatments, namely surgical resection and stereotactic radiosurgery (RS). There is a lack of evidence to support the superiority of surgery or RS as first-line treatment in solitary and oligometastatic brain disease, since previous attempts to systematically review the corpus of evidence have failed to produce any conclusive findings. This systematic review with meta-analysis aims to provide a quantitative synthesis of the results of RCTs investigating the efficacy and safety of surgery compared to RS, combined or not with WBRT, for localized metastatic brain disease. ABSTRACT: Purpose: To analyze the efficacy and safety of surgery compared to radiosurgery (RS), combined or not with whole brain radiotherapy (WBRT), for localized metastatic brain disease. Methods: A systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The inclusion criteria were limited to randomized controlled trials (RCTs) that compared surgery and RS for patients with up to 3 metastases (median diameter ≤ 4 cm). The primary outcomes were represented by overall survival (OS) and local brain progression-free survival (PFS), with the rate of complications as a secondary outcome. The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the RoB2 revised tool and the certainty of the evidence was assessed according to the GRADE guidelines. Results: In total, 11,256 records were identified through database and register searches. After study selection, 3 RCTs and 353 patients were included in the quantitative synthesis. Surgery and RS represented the main intervention arms in all the included RCTs. Conclusions: A low level of evidence suggests that RS alone and surgery followed by WBRT provide an equal rate of local brain PFS in patients with localized metastatic brain disease. There is a very low level of evidence that surgery and RS as main interventions offer equivalent OS in the population investigated. A reliable assessment of the complication rates among surgery and RS was not achievable. The lack of high-certainty evidence either for superiority or equivalence of these treatments emphasizes the need for further, more accurate, RCTs comparing surgery and RS as local treatment in patients with oligometastatic brain disease.