9550 Background: Melanoma brain metastases (MBM) carry a poor prognosis and remain understudied in prospective trials. Dual immune checkpoint blockade (ICB) with nivolumab plus ipilimumab (N+I) achieves durable intracranial responses; stereotactic radiosurgery (SRS) is sometimes added but its survival benefit is unclear. Despite the increasing real-world use of SRS in combination with dual ICB, no prior meta-analysis has compared survival outcomes of N+I + SRS versus N+I alone. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.PubMed, Embase, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) and observational/real-world (ORW) studies published from January 2015 to July 1, 2025. Primary outcomes were overall survival (OS) and progression-free survival (PFS).Secondary outcomes included radiologic responses rates assessed by RECIST 1.1 and prognostic biomarkers. Random-effects models were used to pool risk ratios (RRs) and hazard ratios (HRs) with 95%confidence intervals (CIs). Analyses were performed in RevMan and R. Results: From 2,972 records, a total of thirteen studies included (ten ORW studies and three RCTs) met our inclusion criteria, including 2,055 patients. Median age was 57.2 years and 64.28% were male. N+I + SRS significantly improved OS compared with N+I alone (HR = 0.56; 95% CI, 0.44–0.71; p2× upper limit of normal) was observed in 37% of patients (95% CI, 20–58) and was associated with inferior survival outcomes. Conclusions: In patients with MBM, the addition of stereotactic radiosurgery with dual immune checkpoint blockade is associated with significant overall survival advantage compared with N+I alone. This first meta-analysis defines the incremental survival benefit of adding SRS to contemporary dual immunotherapy N+I integrating long-term survival outcomes, radiologic response, and prognostic biomarkers. These findings support N+I as the systemic backbone for MBM management and support SRS integration for appropriately selected patients. Prospective trials are warranted to optimize sequencing,timing, and patient selection.
Ortíz et al. (2026) studied this question.