Stereotactic radiosurgery (SRS) alone vs SRS + whole-brain radiotherapy (WBRT) for 1–4 brain metastases: Meta-analysis of randomized controlled trials.

e14008 Background: Whether adding WBRT to SRS improves survival for patients with limited brain metastases remains controversial. WBRT improves intracranial control but may worsen cognition and quality of life. We performed an RCT-only meta-analysis to quantify effects on survival, brain control, neurocognition, and toxicity. Methods: We searched PubMed/Embase/Cochrane/Central from 2000–2025 for randomized trials comparing SRS alone vs SRS + WBRT in adults with 1–4 brain metastases. Outcomes: overall survival (OS), intracranial progression (any brain failure), local control at treated sites, neurocognitive decline (as defined per trial), and grade ≥3 toxicity. Pooled hazard ratios (HR) for time-to-event and risk ratios (RR) for binary outcomes were calculated using a random-effects model; heterogeneity with I². Risk of bias was assessed with RoB 2. Results: Six RCTs (n≈1,250) met criteria across melanoma, NSCLC, and mixed primaries; median follow-up 6–15 months. Risk of bias was low to moderate (open-label design common). OS: No significant difference between SRS alone and SRS + WBRT (pooled HR ~1.00, 95% CI approx. 0.87–1.15; I² low). Intracranial progression (any brain failure): Significantly less with SRS + WBRT (pooled HR ~0.55, 95% CI 0.45–0.67). Local control at treated lesions: Improved with addition of WBRT (pooled RR ~1.15, 95% CI 1.06–1.25). Neurocognitive decline: Higher after SRS + WBRT (pooled RR ~1.8, 95% CI 1.4–2.4), consistent across test batteries; quality-of-life favored SRS alone at 3 months. Grade ≥3 toxicity: Similar between arms overall; alopecia and fatigue more frequent with WBRT; radiosurgery-related serious AEs were rare in both arms. Conclusions: Across randomized trials, adding WBRT to SRS does not improve overall survival for patients with 1–4 brain metastases, despite better intracranial control. The trade-off is worse neurocognitive outcomes and lower short-term quality of life with WBRT. For appropriately selected patients, SRS alone is a reasonable standard, reserving WBRT for salvage or high-risk scenarios. Ongoing trials of hippocampal-avoidance WBRT and systemic therapy combinations may refine patient selection Pooled effects (SRS alone vs SRS + WBRT; RCTs only). Outcome Metric Pooled effect 95% CI Direction Overall survival HR ~1.00 0.87–1.15 No difference Any intracranial progression HR ~0.55 0.45–0.67 ↓ with WBRT Local control (treated sites) RR ~1.15 1.06–1.25 ↑ with WBRT Neurocognitive decline RR ~1.80 1.40–2.40 ↑ with WBRT Grade ≥3 toxicity RR ~1.10 0.85–1.40 Similar