ABSTRACT
BACKGROUND: Recent therapeutic advances in metastatic melanoma have led to improved overall survival (OS) rates, with consequently an increased incidence of brain metastases (BM). The role of BM resection in the era of targeted and immunotherapy should be reassessed. In the current study we analysed the role of residual intracranial tumour load in a cohort of melanoma BM patients. METHODS: Retrospective single-centre analysis of a prospective registry of resected melanoma BM from 2013 to 2021. Correlations of residual tumour volume and outcome were determined with respect to patient, tumour and treatment regimens characteristics. RESULTS: 121 individual patients (66% male, mean age 59.9 years) were identified and included in the study. Pre- and postoperative systemic treatments included BRAF/MEK inhibitors, as well as combination or monotherapy of immune-checkpoint inhibitors (ICIs). Median OS of the entire cohort was 20 months. Cox proportional-hazard analysis revealed postoperative anti-CTLA4+anti-PD-1 therapy (HR 0.07, p = .01) and postoperative residual intracranial tumour burden (HR 1.4, p = .027) as significant predictors for OS. Further analysis revealed that ICI-naïve patients with residual tumour volume ≤3.5 cm3 and postoperative ICI showed significantly prolonged OS compared to patients with residual volume >3.5 cm3 (p < .0001). Subgroup analysis of ICI-naïve patients showed steroid intake postoperatively to be negatively associated with OS, however residual tumour volume ≤3.5 cm3 remained independently correlated with superior OS (HR 0.14, p < .001). CONCLUSION: Besides known predictive factors like postoperative ICI, a maximal intracranial tumour burden reduction seems to be beneficial, especially in ICI-naïve patients. This highlights the importance of local CNS control and the need to further investigating the role of initial surgical tumour load reduction in randomised clinical trials.