Epidemiology of brain metastases and the clinical value of treatment: a narrative review

Article information

J Korean Med Assoc. 2026;69(7):524-529

Publication date (electronic) : 2026 July 10

doi : https://doi.org/10.5124/jkma.26.0030

Yoon Hwan Byun, MD

Department of Neurosurgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea

Corresponding author: Yoon Hwan Byun E-mail: midgetsumo@snu.ac.kr

Received 2026 March 14; Accepted 2026 June 6.

Abstract

Introduction

Epidemiology of brain metastases

Brain metastases are the most frequently diagnosed intracranial tumors in adults [3,4]. Their incidence has been reported to be up to 10 times higher than that of primary malignant brain tumors [5]. Approximately 10%–20% of patients with solid tumors develop central nervous system metastases during their disease course [6,7]. Population-based and autopsy studies have yielded variable estimates, with the prevalence of brain metastases generally cited as 8.3–14.3 per 100,000 population [1]. Lung cancer, breast cancer, and melanoma are the most common primary malignancies [8,9], and the cerebral hemispheres are the most frequent sites of involvement, followed by the cerebellum and brainstem [10,11].

The incidence of brain metastases is generally considered to be increasing, a trend supported by several population-based studies [12–15]. This increase has been attributed to the combined effects of higher cancer prevalence associated with population aging [16], prolonged survival resulting from advances in systemic therapy [1], and improved detection driven by advances in neuroimaging [17].

Limitations of epidemiological studies on brain metastases

The true incidence of brain metastases has not been precisely established. Many existing epidemiological studies are based on data collected before the widespread adoption of modern neuroimaging techniques and contemporary systemic therapies, and nationwide population-based datasets are often unavailable. To address these limitations, some studies have used insurance claims data [18,19].

The Surveillance, Epidemiology, and End Results (SEER) database, a United States cancer registry, is widely used in epidemiological research on central nervous system tumors and is reported to represent approximately 26.5% of the US population [8]. However, SEER captures only synchronous brain metastases present at the time of primary cancer diagnosis and does not include metachronous brain metastases that develop after the primary diagnosis [9]. This limitation is a major source of underrepresentation of patients with brain metastases in SEER-based analyses. In addition, the timing of metachronous brain metastases varies by primary tumor type, which may affect reported incidence rates and the interpretation of survival outcomes for individual primary malignancies. For example, brain metastases from lung cancer tend to be identified relatively early after primary diagnosis, whereas those from breast and colorectal cancer are often diagnosed after a latency period of several years [20,21].

Brain imaging surveillance guidelines also differ by primary tumor type, which may affect reported brain metastasis incidence rates. Brain magnetic resonance imaging (MRI) screening is recommended for small-cell lung cancer [22], but it is not universally indicated for all patients with breast cancer [23]. Imaging modality is another important variable: computed tomography has low sensitivity for small lesions, and contrast-enhanced MRI with a slice thickness of 1.5 mm or less is required for accurate diagnosis [24]. Differences in national healthcare policy and access to neuroimaging may also influence reported brain metastasis incidence rates across countries.

Epidemiological studies on brain metastases

In a SEER-based study, Parker et al. [8] reported that the incidence of synchronous brain metastases in the United States during 2015–2019 was 7.1 per 100,000 population. Age-specific incidence rates were 0.14 per 100,000 in children aged 0–14 years, 0.51 per 100,000 in adolescents and young adults aged 15–39 years, and 16.03 per 100,000 in adults aged 40 years or older. Lung cancer was the most common primary malignancy, followed by melanoma and breast cancer. Among children, renal cancer was the most frequent primary tumor.

Jiang et al. [25] conducted a large-scale analysis that included metachronous brain metastases using the TriNetX Research Network, which integrates de-identified electronic health records and administrative claims data from healthcare institutions in the United States. Among 11,497,663 patients analyzed, brain metastases developed in 300,863 (2.6%), of whom 62.2% had metachronous disease.

In Korea, Kim et al. [26] analyzed the epidemiology of brain metastases using a sample cohort from the National Health Insurance Service database. During the 9-year observation period (2005–2013; 8,725,438 person-years), brain metastases were identified in 776 patients. The age-standardized incidence was 8.2 per 100,000 person-years, with an estimated 4,540 new cases annually. Lung cancer was the predominant primary malignancy, with approximately 2,440 new brain metastasis cases per year estimated to be attributable to lung cancer. Notably, brain metastases from hepatic malignancies accounted for a comparatively high proportion of cases (6.2%), a finding interpreted as reflecting the high incidence of hepatocellular carcinoma and the trend toward prolonged survival in Korea [27].

A study using Canadian Cancer Registry data from 2010 to 2017 [28] reported that an annual average of approximately 3,227 patients presented with synchronous brain metastases at the time of primary cancer diagnosis. Among primary malignancies, lung cancer had the highest rate of concurrent brain metastases, at 9.42%.

A single-center study from a tertiary referral center in the United States [29] reported a decreasing proportion of brain metastases originating from breast cancer and melanoma and an increasing proportion originating from primary malignancies historically less commonly associated with brain metastases, including prostate, ovarian, and bladder cancers. These shifts suggest that new approaches to screening, prognostication, and treatment planning for brain metastases may be warranted.

Survival outcomes of brain metastases

Conventional systemic therapies often fail to penetrate the blood–brain barrier adequately; therefore, local therapies, including radiation therapy and surgical resection, have formed the cornerstone of brain metastasis treatment [30]. However, recent advances in targeted therapy and immunotherapy have led to consideration of systemic therapy as an initial treatment option for selected patients with brain metastases, particularly those with lung cancer [6,31]. In addition, in a study of patients with 5 to 20 brain metastases, stereotactic radiosurgery was associated with overall survival comparable to that of hippocampal-avoidance whole-brain radiotherapy while better preserving functional independence and performance status [32]. This approach is now being used more broadly. Despite these therapeutic advances, the overall prognosis of patients with brain metastases remains poor. SEER-based studies have reported a median overall survival of 12 months or less in patients with synchronous brain metastases across most primary tumor types [33]. Among patients aged 65 years or older with metachronous brain metastases, median survival has been reported to be as low as 4 months or less [34]. In contrast, clinical trials employing the Graded Prognostic Assessment have reported a somewhat more favorable median survival of 8–16 months [35], a finding that may partly reflect patient selection bias.

Epidemiology and survival outcomes of leptomeningeal disease

Leptomeningeal disease is a pattern of metastatic spread in which tumor cells disseminate along the leptomeninges and cerebrospinal fluid spaces [36]. It is identified in approximately 2%–12% of patients at the time of initial brain metastasis diagnosis and has been reported to develop de novo in 1%–37% of patients during the disease course [9]. Postsurgical pachymeningeal seeding, which must be distinguished from leptomeningeal disease, has been reported in approximately 8% of patients after brain metastasis resection [37]. Treatment options for leptomeningeal disease include non-stereotactic radiotherapy, intrathecal chemotherapy, and cerebrospinal fluid diversion. The prognosis is extremely poor, with reported median survival of approximately 4–6 months with treatment and approximately 4–6 weeks without treatment [38].

Clinical significance of early detection and treatment of brain metastases

Treatment of brain metastases aims to achieve intracranial local control, preserve neurological function, and maintain eligibility for systemic therapy. Untreated brain metastases can cause progressive neurological deficits, elevated intracranial pressure, and death from neurological complications [13,39,40]. Preserving neurological function through active treatment is critical for maintaining patients’ eligibility for subsequent systemic therapies, which may in turn provide additional benefit in controlling intracranial disease [41]. Recent studies have highlighted the importance of neurological symptom burden [42]. Steindl et al. [43] reported that neurological symptom burden is an independent predictor of survival in patients with breast cancer brain metastases. Preservation of adequate neurocognitive function is also recognized as closely associated with quality of life in patients with cancer [44].

The prognosis of untreated brain metastases is extremely poor, with a reported median survival of only 1–2 months [45]. Whole-brain radiotherapy may extend survival by approximately 2–4 months, whereas aggressive surgical resection combined with multidisciplinary management is associated with marked improvement in median overall survival, ranging from 7.5 months to more than 20 months, depending on the patient population [46]. Stereotactic radiosurgery, a contemporary treatment strategy, has been reported to achieve high rates of local tumor control, particularly when combined with other modalities [47,48]. Advances in targeted systemic therapy are also improving outcomes in specific tumor types at high risk for brain metastases, including non-small-cell lung cancer, breast cancer, and melanoma [30]. Accordingly, early detection of brain metastases may reduce morbidity and mortality and, secondarily, limit treatment-related toxicity [33]. For these reasons, early detection and proactive multidisciplinary management of brain metastases continue to be emphasized as important strategies in comprehensive cancer care.

Conclusion

Brain metastases are becoming increasingly clinically significant in the context of prolonged cancer survival and ongoing advances in neuroimaging. Treatment of brain metastases can help prevent neurological deterioration, preserve functional status, and enable continuation of systemic therapy. Advances in neurosurgical intervention, radiotherapy, and targeted systemic therapy are expanding available treatment options and improving intracranial disease control. Early detection and multidisciplinary management of brain metastases will therefore remain key clinical priorities.

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