Prognostic Factors among Patients with Brain Metastases from Cancer of Unknown Primary

Abstract Background Cancer of an unknown primary (CUP) has a dismal prognosis, the situation is worse for CUP patients with brain metastases (BM-CUP). This study aimed provides better insight into BM-CUP occurrence and determinants of patients’ survival in a population-based setting. Methods Cases were selected from the Netherlands Cancer Registry (1,430 BM-CUP/17,140 CUP). Baseline characteristics between CUP patients with and without BM were tested using chi-square tests and Mann-Whitney U tests. Patients’ overall survival (OS) curves were estimated by the Kaplan-Meier method, and prognostic factors on OS was assessed using Cox proportional hazards regression analyses. Results The proportion of BM-CUP patients among CUP increased from 8% in 2009–2010 to 10% in 2017–2018 (p < 0.001). Most patients presented with multiple brain lesions (53%). Survival of BM-CUP improved over time: one-year OS increased from 10% for patients diagnosed in 2009–2010 to 17% (2017–2018) (p < 0.01), and median survival times increased from 1.8 months to 2.4 months. Aside from time period and elderly age, independent predictors of poor survival were multiple (HR 1.25; p < 0.01) or unknown (HR 1.48; p < 0.01) locations of BM, unknown/poorly/undifferentiated carcinoma histology (HR 1.53; p < 0.01), or clinical symptoms of BM (HR 1.74; p < 0.01), accompanying liver metastasis (HR 1.43; p < 0.01) and more than one metastatic site outside the brain compared to none (HR 1.52; p < 0.01). Conclusion This research contributes to better knowledge on BM-CUP patients. Comprehensive baseline information aids the implementation and evaluation of new diagnostic approaches, treatment protocols and supportive/palliative care guidelines thus improve patients’ quality of life.