Stereotactic Radiosurgery Versus Whole-Brain Radiotherapy in Patients with Multiple Brain Metastases: Current Evidence and Future Perspectives

Abstract

Brain metastases are among the most common intracranial tumors in adults and represent a major cause of morbidity and mortality in patients with advanced cancer. Historically, whole-brain radiotherapy (WBRT) has been the standard treatment for patients with multiple brain metastases because of its ability to address both visible and microscopic intracranial disease. However, concerns regarding radiation-induced neurocognitive decline and reduced quality of life have led to increasing interest in stereotactic radiosurgery (SRS), a highly precise radiation technique that delivers ablative doses to metastatic lesions while minimizing exposure to surrounding healthy brain tissue. Recent prospective studies, randomized controlled trials, and meta-analyses have demonstrated that SRS alone provides local tumor control and overall survival outcomes comparable to WBRT in selected patients with multiple brain metastases, while significantly preserving cognitive function and maintaining quality of life. Advances in imaging, treatment planning, and radiation delivery have further expanded the role of SRS beyond patients with a limited number of lesions, challenging the traditional paradigm that favored WBRT for extensive intracranial disease. Additionally, the emergence of hippocampal-avoidance WBRT and neuroprotective agents such as memantine has improved the therapeutic ratio of WBRT, although concerns regarding long-term cognitive toxicity remain. This review summarizes current evidence comparing SRS and WBRT with respect to treatment efficacy, intracranial control, neurocognitive outcomes, toxicity profiles, and patient-reported quality of life. Furthermore, it discusses evolving treatment strategies, integration with systemic therapies, technological innovations, and future research directions aimed at optimizing personalized care for patients with multiple brain metastases.

Keywords: Brain metastases; Stereotactic radiosurgery; Whole-brain radiotherapy; Neurocognition; Quality of life; Brain tumors; Radiation oncology