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Patients with leptomeningeal metastases (LM) from non-small cell lung cancer (NSCLC) have a poor outcome with survival of less than 1 year regardless of advancements in treatment strategy. In the past, some randomized clinical trials have been conducted with heterogeneous inclusion criteria, diagnostic parameters, response evaluation and primary endpoints. Efforts to develop a standardized magnetic resonance imaging (MRI) assessment and liquid biopsy techniques to monitor disease evolution in plasma or cerebrospinal fluid (CSF) are underway. This review aims to cover the main clinical and diagnostic challenges of LM from NSCLC, in particular the role of MRI, CSF cytology and liquid biopsy for the diagnosis and monitoring of the disease, as well as the most recent clinical trials on targeted therapies. Targeted therapy, such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase rearranged inhibitors, represent a feasible treatment with encouraging results in terms of disease control and survival. For ineligible patients, immune checkpoint inhibitors could represent a therapeutic option with acceptable tolerance, although clinical trials focused on LM from NSCLC are lacking and represent a research focus for the future.

Leptomeningeal metastases from non-small cell lung cancer: state of the art and recent advances