Adding WBRT to SRS cuts brain metastasis recurrence but raises cognitive decline without survival gain

INTRODUCTION: Brain metastases represent the most common intracranial tumors in adults. Stereotactic radiosurgery (SRS) is widely used for their management. However, the role of SRS plus adjunct whole-brain radiotherapy (WBRT), remains debated given the risk of neurocognitive deterioration (NCD). We conducted a comparative analysis of SRS alone versus SRS combined with WBRT in patients with brain metastases. METHODS: We identified studies evaluating SRS alone or in combination with WBRT for the management of brain metastases. Our outcomes of interest included NCD, Overall Survival (OS), Local Tumor Control (LTC), and radionecrosis (RN). RESULTS: We analyzed 6 cohort studies and 4 randomized controlled trials including 1,757 patients. OS was comparable between groups (HR = 1.06;95%CI = 0.86-1.30;p = 0.60). LTC in the SRS-alone group was 77.71%, while SRS+WBRT group achieved a 87.25% of LTC which was comparable between groups (RR = 1.17;95%CI = 0.99-1.39;p = 0.07;I = 82%). Recurrence rate was 13.9% in SRS+WBRT and 37% with SRS alone, favoring SRS+WBRT (RR = 0.37; CI95%=0.21-0.65, p = 0.0005; I = 0%). RN rate for was 3.7% with SRS+WBRT and 3.5% with SRS alone, which were comparable (RR = 0.99; CI95%=0.33-2.93, p = 0.98; I = 0%). NCD of ≥1SD from baseline was more frequent in the SRS+WBRT group (RR = 0.64;95%CI = 0.47-0.87;p = 0.005). CONCLUSION: SRS is an effective and safe therapy for metastatic brain disease. While its combination with WBRT may improve recurrence rates with stable LTC and limited RN rates, it is associated with higher rates of NCD without a clear OS benefit. Future trials should assess homogeneous populations and integrate quality-of-life outcomes to guide individualized treatment selection. CLINICAL TRIAL NUMBER: Not applicable.