Treatment modalities in recurrent brain metastases: a combined institutional and individual patient data meta-analysis of post-recurrence survival and local progression-free survival.

Abstract

<h4>Background</h4>Brain metastases (BM) are among the most common intracranial tumors. Despite advances in multimodal therapy for newly diagnosed BM, the management of recurrent BM remains a clinical challenge. Due to the lack of robust data, there is currently no consensus regarding optimal salvage treatment for recurrent BM.<h4>Methods</h4>Institutional data (2016-2025) and published data from the literature (2011-2025) were analyzed with respect to overall survival (OS) and progression-free survival (PFS) after recurrence. Survival data were extracted from Kaplan-Meier curves of the selected studies using the R package IPDfromKM and pooled survival analyses were performed.<h4>Results</h4>In a pooled analysis of 776 patients, local surgical re-resection after recurrence was associated with significantly longer survival compared to both non-surgical management (median 14.74 [95% CI: 11.68-17.80] vs. 10.34 months [95% CI: 8.59-12.08]; HR: 0.664; p < 0.001) and only repeat stereotactic radiosurgery (Re-SRS) (median 14.74 months [95% CI: 10.51-18.98] vs. 10.97 months [95% CI: 9.1-12.84]; HR: 0.62; p < 0.001). Among patients who underwent local re-resection, gross total resection (GTR) led to markedly improved OS compared to subtotal or incomplete resection (median 23.97 months [95% CI: 15.95-31.99] vs. 7.06 months [95% CI: 5.21-8.90]; HR: 0.400; p < 0.0001). The addition of adjuvant re-radiotherapy after re-resection did not result in a significant survival benefit (p = 0.357). Regarding PFS, patients treated with local re-resection alone had the longest median PFS (43.23 months), significantly outperforming both those receiving re-resection plus adjuvant re-SRS (29.92 months; HR = 0.529; p < 0.001) and those treated with Re-SRS alone (15.79 months; HR = 3.031; p < 0.001).<h4>Conclusions</h4>This study highlights the role of local re-resection in improving survival among patients with recurrent brain metastases amenable to repeat GTR. Re-SRS remains a valuable salvage option, particularly for patients in whom GTR is not feasible. While adjuvant re-radiotherapy following re-resection did not demonstrate a clear survival advantage in our analysis, it may offer additional local control in selected cases. These findings emphasize the importance of individualized, multidisciplinary decision-making to tailor salvage strategies to patient- and tumor-specific factors.