The Link Between LEMS and Cancer

Patients with SCLC-LEMS have an improved tumor survival compared to patients with SCLC without LEMS.41

—Lipka et al, 2020

The benefits of earlier diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) include limiting disability along with the loss of muscle function, mobility, and quality of life for patients. But for more than half of patients afflicted with LEMS, the benefits of diagnosis are often even more significant.3,4

Approximately 60% of LEMS cases are caused by an underlying tumor, typically small cell lung cancer (SCLC).42 The reported median time between onset of LEMS and a subsequent cancer diagnosis is 6 months.9 Patients with SCLC-LEMS are more frequently found while still having limited disease.41 With regular screening, most SCLCs can be discovered within 1 year of a LEMS diagnosis.9,43

In this section, we’ll present clinical and practical information that will help you better understand the relationship between these two diseases and how you can use these insights to improve clinical outcomes for your patients.

Mazen Dimachkie, MD, is a leading consultant in the study of LEMS. As the Director of Neuromuscular Research at the University of Kansas Medical Center, he manages one of the busiest neuromuscular clinical trial units in North America.

NeuroseriesLive hosted a webinar featuring Dr. Dimachkie discussing LEMS: “Are My Muscles Aging? One Often-misdiagnosed Cause of Weakness and Fatigue.” Excerpts from this program appear throughout this website, and you can watch the full webinar here.*

*Sponsored by Catalyst Pharmaceuticals.


Paraneoplastic syndromes of the nervous system are a heterogeneous group of neurological disorders caused by the immune response to an underlying tumor—specifically, against the onconeural antigen expressed by both the tumor and the nervous system. These syndromes are not caused by cancer metastasis. LEMS is considered a classic example of this syndrome.44


In up to 80% of patients with paraneoplastic syndromes of the nervous system,
the neurological disorder develops before the tumor is detected44,45

3 categories of paraneoplastic syndromes of the nervous system

Syndromes of the central nervous system

Syndromes of the central nervous system46

Examples of central nervous system syndromes include encephalomyelitis, limbic encephalitis, and cancer-related retinopathy

Syndromes of the central nervous system

Syndromes of the peripheral nervous system46

Examples of peripheral nervous system syndromes include Guillain-Barré syndrome and certain neuropathies

Syndromes of the central nervous system

Syndromes of the neuromuscular junction and muscle46

LEMS and myasthenia gravis are the most common syndromes of the neuromuscular junction6,46

Timely diagnosis
Timely diagnosis, prompt symptomatic neurological treatment, and treatment of the underlying malignancy are essential components of management of these cases.29


The cancers most commonly
associated with LEMS9

In a 155-publication review describing 227 cases of LEMS9:

  • 62% of patients were found to have cancer-related LEMS (n=141)
  • Among 24 different tumor types associated with LEMS, 79% were pulmonary malignancies (n=112)
    • 84% of those pulmonary malignancies were small cell lung cancer (SCLC)
Cancer Chart
Cancer ChartCancer Chart

*Carcinomas of the breast, maxillary glandule, laryngeal area, and gallbladder, along with rectal adenocarcinoma, malignant thymoma, ameloblastoma, other pulmonary malignancies, and lymph metastasis (unknown primary site).


In a Neurology 2020 observational study, “Long-term follow-up, qualify of life, and survival of patients with Lambert-Eaton myasthenic syndrome,” Lipka et al detail the findings of 150 patients with LEMS—54% related to small cell lung cancer (SCLC).41

Key insights from this study include41:

  • Rates of cancer survival
  • Progression of LEMS symptoms
  • Impact of LEMS on quality of life
  • Results of treatment of LEMS symptoms using immunosuppressive and neuromuscular junction modulating therapies

Study design41

  • Observational study using data collected between July 1998 and October 2015
  • 150 patients diagnosed with LEMS, based on characteristic clinical features, and confirmed by either the presence of antibodies to voltage-gated calcium channels or abnormal decrement and 60% increment on repetitive nerve stimulation
  • 59% of patients (85) had an associated lung cancer


Patients with SCLC-LEMS had an improved tumor survival vs patients with SCLC alone41

Survival ChartSurvival Chart
  • Among 81 patients with SCLC-LEMS, survival was significantly longer compared with patients with SCLC without LEMS (17 months vs 7 months, respectively, P<0.0001)41
  • Patients with SCLC-LEMS are more frequently found while still having limited disease41
  • Among 65 patients with non-tumor LEMS, the average life expectancy was similar to the healthy population41
Progression of LEMS

Progression of LEMS

  • 73% of LEMS patients used a mobility-assistance device at some point during the course of disease (median follow-up time: 12-130 months)41
  • 52% used a wheelchair, and 6% were fully wheelchair-dependent at any point during their disease course41
  • Patients with SCLC-LEMS reported more functional impairment at any point in their disease course vs non-tumor LEMS41
  • Median time from onset of LEMS symptoms to diagnosis was 18 months in patients without SCLC vs 4 months in patients with SCLC41
  • Median time from onset of LEMS symptoms to maximum disease severity was 12 months for non-tumor LEMS vs 4 months in patients with SCLC41
Progression of LEMS

Quality of Life

  • Surviving subjects participated in a 36-question survey to determine their Health-Related Quality of Life (HRQoL) with SCLC41
    • 8 domains of HRQoL were examined, including physical functions; physical role limitations due to physical problems; bodily pain; general health evaluation; vitality; social functioning; emotional role limitations due to emotional problems; and mental health
    • Responses were compiled to produce a physical composite score (PCS) and mental composite score (MCS)
  • Non-tumor and tumor-LEMS patients both reported lower HRQoL scores vs the general population41
  • PCS was lower for tumor-LEMS patients than for non-tumor LEMS patients41
    • MCS was comparable between tumor and non-tumor LEMS patients41


  • Among patients who received symptomatic treatment with 3,4-DAP or pyridostigmine, 88% reported improvement in symptoms due to 3,4-DAP vs only 67% who reported improvement due to pyridostigmine (N=150)41
    • Effects of pyridostigmine may be short-lived
  • Patients treated with symptomatic therapy appeared to improve sooner after diagnosis vs those treated with immunosuppressive drugs41

Median survival is doubled in patients with SCLC-LEMS with extensive disease compared to patients with SCLC without LEMS, and overall 5-year survival is increased from 4.4% to 21%.41

—Lipka et al, 2020

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