Surgical tumor volume reduction in patients with brain metastases: A systematic review and meta-analysis

Background: Microsurgical resection of brain metastases (BM) has traditionally been a mainstay of local control for large or symptomatic lesions. Maximal tumor burden reduction remains controversial in the multidisciplinary management of BM patients and needs to be re-evaluated in view of new systemic treatment options. We conducted a systematic review and meta-analysis to evaluate the role of extent of resection (EOR)/residual volume (RV) for progression-free (PFS) and overall survival (OS) in patients with BM. Methods: A systematic review was performed according to PRISMA guidelines and included studies’ quality was assessed with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Study characteristics were tabulated and critically reviewed. Results from Cox-regression models and log-rank tests for the association of gross total resection (GTR) versus subtotal resection (STR) with PFS and OS were extracted to perform separate random-effects meta-analyses. Results: Thirty-nine articles were included, all of them being retrospective and all but 3 monocentric. Most studies included BM from heterogenous primary tumors, with 9 focusing on BM from a single primary. Systemic therapies were variably reported and only 2 studies reported on the use of steroids. Twenty-one studies showed a significant association of EOR/RV with improved OS. Meta-analysis of studies reporting multivariable Cox-regression models (n = 11) showed a significant association of GTR with longer OS (HR 0.67, 95 %CI 0.56–0.81, p < 0.001). Conclusion: Although in several studies higher EOR/lower RV was associated with improved OS, evidence consists of heterogeneous cohorts and rarely includes primary tumor-specific systemic therapies or relevant confounding covariates. New studies are needed to elucidate the role of microsurgical tumor burden reduction in BM patients in the era of targeted or immune modulatory therapies.