Dr Sands on Challenges in the Diagnosis and Management of LEMS in SCLC

“The tough thing is that the symptoms of LEMS are quite common in general, and someone with small cell lung cancer, especially [during] treatment, [may feel] some weakness. One of the more classic symptoms of LEMS is proximal muscle weakness…[With] any kind of weird stuff that's going on neurologically without a good description for it, I would consider paraneoplastic syndromes associated with small cell lung cancer that can be LEMS.”

Jacob Sands, MD, associate chief of the Lowe Center for Thoracic Oncology and oncology medical director of the International Patient Center at Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, discussed key challenges in the diagnosis and management of Lambert-Eaton myasthenic syndrome (LEMS) in patients with small cell lung cancer (SCLC), emphasizing the need for heightened clinical suspicion and systematic neurologic evaluation in this population.

According to Sands, one of the primary difficulties in identifying LEMS in patients with SCLC lies in the nonspecific nature of its presenting symptoms. Proximal muscle weakness, a hallmark feature of LEMS, can also be common among patients with SCLC for a variety of reasons, according to Sands, including cancer-related fatigue, deconditioning, and adverse effects of systemic therapy. As a result, early manifestations of LEMS may be mistakenly attributed to chemotherapy or the general burden of illness, leading to under recognition of this paraneoplastic syndrome.

Autonomic dysfunction further complicates the clinical picture. Sands noted that symptoms such as orthostatic hypotension, dry mouth, constipation, or other vague neurologic complaints may be subtle and easily overlooked. In clinical practice, these “unusual” or poorly characterized neurologic symptoms should prompt consideration of paraneoplastic etiologies, particularly in patients with SCLC, which has a strong association with immune-mediated neurologic syndromes. Although the discussion focused on LEMS, Sands underscored that other paraneoplastic neurologic disorders—some also seen in non–small cell lung cancer—should remain part of the differential diagnosis.

From a diagnostic standpoint, Sands advocated for a low threshold to initiate a formal paraneoplastic workup in patients with SCLC who develop neurologic dysfunction. This includes ordering a comprehensive paraneoplastic antibody panel and involving neurology early in the evaluation. Given the overlap between treatment-related toxicities and paraneoplastic symptoms, reliance on clinical gestalt alone may result in missed diagnoses. Sands highlighted that this is a persistent source of concern in practice, as clinicians may prematurely conclude that neurologic symptoms are therapy related without pursuing additional testing.