Systematic review evaluates survival benefits and cognitive effects of PCI in LS-SCLC, suggesting a favorable profile.
Background: The necessity of prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) is increasingly debated in the era of high-resolution magnetic resonance imaging (MRI). This meta-analysis evaluated the survival and neurocognitive effects of PCI in LS-SCLC patients confirmed negative for brain metastases (BM) by pre-PCI MRI. Methods: Following PRISMA guidelines, a systematic search of PubMed, Embase, and Cochrane Library was conducted through 23 September 2025. Pooled hazard ratios (HRs) and risk ratios (RRs) were calculated to assess overall survival (OS), progression-free survival (PFS), brain metastasis-free survival (BMFS), and BM rate. Results: Eleven studies involving 1894 patients were synthesized. PCI conferred a significant survival advantage, reducing the risk of death by 31% (HR = 0.69, 95% CI: 0.61–0.78), which translated to an absolute OS improvement of 8.5% at 2 years and 6.5% at 5 years. Substantial improvements were also observed in PFS (HR = 0.71, 95% CI: 0.60–0.84) and BMFS (HR = 0.53, 95% CI: 0.32–0.88), alongside a 36% reduction in BM rate (RR = 0.64, 95% CI: 0.53–0.77). Notably, PCI maintained its OS benefit even when compared directly against active MRI surveillance. While neurocognitive adverse events were reported, evidence suggests that these effects are predominantly transient and domain-specific, without a sustained decrease in global quality of life. Conclusions: In the MRI-staging era, PCI remains a significant therapeutic option for LS-SCLC. It offers a favorable risk–benefit profile by significantly enhancing survival while maintaining manageable neurocognitive safety.
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