Representation of Surgery in Registered Clinical Trials for Brain Metastases: An Analysis of the ClinicalTrials.gov Database

Background/Objectives: Brain metastases (BMs) represent a significant clinical challenge affecting 10–26% of patients who die from cancer. While surgery plays an established role in the management of selected patients, its representation within the registered clinical trial landscape has not been systematically characterized. Methods: In this cross-sectional registry analysis, ClinicalTrials.gov was searched on 20 December 2025, using condition terms related to BMs combined with the Boolean operator OR. Interventional and observational studies were included without restrictions on phase, status, sex, or age; trials not updated since 1 January 2015 were excluded. Included studies were classified as surgery-focused, surgery-enabled, or non-surgical. Data were extracted on study characteristics, interventions, and outcomes. Results: A total of 493 trials were included. Of these, 57 (11.6%) involved surgery, including 9 (1.8%) surgery-focused and 48 (9.7%) surgery-enabled trials, whereas 436 (88.4%) were non-surgical. Radiotherapy was the dominant treatment platform, present in 262 trials (53.1%), with stereotactic radiosurgery reported in 179 (36.3%). Among the 57 surgical trials, the most common primary endpoint categories were periprocedural/safety and local control outcomes (each 26/57, 45.6%) and survival (20/57, 35.1%). Only 4 surgical trials (7.0%), all surgery-focused, had a primary endpoint that directly measured an operative outcome. Conclusions: Surgery accounted for a minority of registered brain metastasis trials and more commonly served as context for evaluating adjuvant, radiation-based, and multimodality approaches than as the primary intervention under study. Surgical trials were weighted toward safety, local control, and survival endpoints, with less frequent emphasis on surgery-specific and functional outcomes.