Background: Despite advances in treatment for brain metastases (BMs), the prognosis for recurrent BMs remains poor and requires further research to advance clinical management and improve patient outcomes. In particular, data addressing the impact of tumor volume and surgical resection with regard to survival remain scarce. Methods: Adult patients with recurrent BMs between December 2007 and December 2022 were analyzed. A distinction was made between operated and non-operated patients, and the residual tumor burden (RTB) was determined by using (postoperative) MRI. Survival analysis was performed and RTB cutoff values were calculated using maximally selected log-rank statistics. In addition, further analyses on systemic tumor progression and (postoperative) tumor therapy were conducted. Results: In total, 219 patients were included in the analysis. Median age was 60 years (IQR 52–69). Median preoperative tumor burden was 2.4 cm³ (IQR 0.8–8.3), and postoperative tumor burden was 0.5 cm³ (IQR 0.0–2.9). A total of 95 patients (43.4%) underwent surgery, and complete cytoreduction was achieved in 55 (25.1%) patients. Median overall survival was 6 months (IQR 2–10). Cutoff RTB in all patients was 0.12 cm³, showing a significant difference (p = 0.00029) in overall survival (OS). Multivariate analysis showed preoperative KPSS (HR 0.983, 95% CI, 0.967–0.997, p = 0.015), postoperative tumor burden (HR 1.03, 95% CI 1.008–1.053, p = 0.007), and complete vs. incomplete resection (HR 0.629, 95% CI 0.420–0.941, p = 0.024) as significant. Longer survival was significantly associated with surgery for recurrent BMs (p = 0.00097), and additional analysis demonstrated the significant effect of complete resection on survival (p = 0.0027). In the subgroup of patients with systemic progression, a cutoff RTB of 0.97 cm³ (p = 0.00068) was found; patients who had received surgery also showed prolonged OS (p = 0.036). Single systemic therapy (p = 0.048) and the combination of radiotherapy and systemic therapy had a significant influence on survival (p = 0.036). Conclusions: RTB is a strong prognostic factor for survival in patients with recurrent BMs. Operated patients with recurrent BMs showed longer survival independent of systemic progression. Maximal cytoreduction should be targeted to achieve better long-term outcomes.

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