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

TL;DR

This study finds that re-surgery improves survival for patients with recurring brain metastases compared to other treatments.

Contribution

A combined institutional and individual patient data meta-analysis provides new evidence on optimal salvage treatments for recurrent brain metastases.

Findings

Local re-resection after recurrence significantly improves survival compared to non-surgical management and repeat stereotactic radiosurgery.

Gross total resection during re-resection leads to much better survival than subtotal or incomplete resection.

Adjuvant re-radiotherapy after re-resection does not significantly improve survival but may offer local control in some cases.

Abstract

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.

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.

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).

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.

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