Comparative outcomes of prophylactic cranial irradiation and brain surveillance in limited-stage small cell lung cancer: A systematic review and meta-analysis.

Abstract

e20142 Background: Prophylactic cranial irradiation (PCI) improves survival outcomes versus no PCI in limited-stage small-cell lung cancer (LS-SCLC), but prior trials predated routine brain MRI; the benefit over modern MRI/CT surveillance is unclear as the phase 3 MAVERICK trial is ongoing. We performed a meta-analysis to compare PCI with routine imaging surveillance and inform practice in the modern imaging era. Methods: We systematically searched PubMed, Embase, and the Cochrane Library for studies published from 2023 to November 18, 2025. We included patients with LS-SCLC in complete or partial remission without brain metastases confirmed by brain MRI or CT. The intervention was PCI; the comparator was routine brain MRI or CT surveillance. The primary outcome was overall survival (OS); secondary outcomes were brain metastasis–free survival (BMFS) and progression-free survival (PFS). Outcomes were summarized as hazard ratios (HRs). When HRs were not reported, they were estimated from Kaplan–Meier curves. Random-effects models were used, and heterogeneity was summarized with I². Analyses were performed in R (version 4.4.2). For studies with propensity score matching (PSM), matched cohorts were used for meta-analysis. Results: A total of 714 patients receiving PCI and 709 patients managed without PCI were included across eight studies. The meta-analysis used propensity score–matched (PSM) cohorts when available (six studies) and full cohorts from two non-PSM studies. Across included cohorts, first-line therapy was radiotherapy with or without concurrent or sequential chemotherapy in 1,327 (92.2%) patients and thoracic surgery in 112 (7.8%) patients. None of the included studies reported whether immunotherapy was used as first-line therapy. The timing of surveillance brain imaging varied across studies, ranging from every 3–4 months during the first 1–2 years, every 3–6 months during years 2–3, and every 3–12 months thereafter. Additionally, the timing and regimens of salvage treatments differed among studies. For OS (8 studies), PCI was associated with better survival (pooled HR 0.74, 95% CI 0.57-0.96; I² = 56.5%, Q = 16.11). For PFS (3 studies), PCI was related to improved outcomes (pooled HR 0.77, 95% CI 0.65- 0.90; I² = 0.0%, Q = 0.44). For BMFS (4 studies), PCI was linked to superior BMFS (pooled HR 0.37, 95% CI 0.25- 0.54; I² = 0.0%, Q = 2.67). Conclusions: Compared with imaging surveillance, PCI was associated with improved OS, PFS, and BMFS in LS-SCLC patients. Heterogeneity among comparator follow-up strategies underscores the need for randomized trials reporting survival outcomes and long-term neurocognitive effects. These findings may help inform clinical decision-making while awaiting results from the ongoing MAVERICK randomized trial.