What are the paraneoplastic syndromes associated with lung cancer?

From the Guidelines

Paraneoplastic syndromes in lung cancer, particularly small cell lung cancer (SCLC), should be promptly recognized and treated to minimize complications and improve patient outcomes, as they affect about 10-20% of patients and can significantly impact quality of life. The most common paraneoplastic syndromes associated with lung cancer include hypercalcemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), Cushing's syndrome, Lambert-Eaton myasthenic syndrome, and neurological disorders like limbic encephalitis 1. Treatment primarily focuses on addressing the underlying lung cancer through surgery, chemotherapy, radiation, or immunotherapy, as eliminating the tumor often resolves the paraneoplastic symptoms. Specific symptom management may include bisphosphonates for hypercalcemia, fluid restriction for SIADH, or immunosuppressive therapy for neurological manifestations.

Some key points to consider in the management of paraneoplastic syndromes in lung cancer include:

• Early recognition of these syndromes is crucial as they may appear before the cancer is diagnosed and can significantly impact quality of life 1.
• The presence of certain paraneoplastic antibodies, such as anti-Hu or anti-VGCC antibodies, can help confirm the diagnosis and guide treatment approaches 1.
• Patients with paraneoplastic syndromes often require a multidisciplinary approach involving oncologists, neurologists, and other specialists to manage both the cancer and its associated syndromes effectively.
• Delayed diagnosis of paraneoplastic syndromes may lead to increased complications that limit or delay cancer treatment, highlighting the need for rapid recognition, proper evaluation, and timely intervention 1.

In terms of specific management strategies, the use of metyrapone, ketoconazole, etomidate, mitotane, and mifepristone can be effective in decreasing circulating glucocorticoids in patients with Cushing's syndrome, while laparoscopic bilateral adrenalectomy can rapidly decrease circulating cortisol levels to allow patients with rapidly progressive SCLC and ectopic Cushing's syndrome to begin chemotherapy in a timely manner 1. Additionally, the use of bisphosphonates for hypercalcemia, fluid restriction for SIADH, or immunosuppressive therapy for neurological manifestations can be effective in managing specific paraneoplastic symptoms. Overall, a comprehensive and multidisciplinary approach is necessary to effectively manage paraneoplastic syndromes in lung cancer patients.

From the Research

Paraneoplastic Syndrome in Lung Cancer

• Paraneoplastic syndromes occur commonly in patients with lung cancer, especially cancers of neuroendocrine origin 2.
• These syndromes can be the first clinical manifestation of malignant disease or a harbinger of cancer recurrence 2, 3.
• Paraneoplastic syndromes can be categorized by common causative mechanisms: hormonal syndromes, autoimmune syndromes, and other syndromes of less clear cause 2.

Epidemiology and Pathogenesis

• Paraneoplastic syndromes occur in approximately 10% of all patients with lung cancer 3.
• The syndromes can be distinguished based on their clinical symptoms, including endocrine, haematological, neuromuscular, dermatological, renal, and metabolic syndromes 3.
• Recent advances in medical technology have allowed better understanding of these syndromes and the development of novel diagnostic and therapeutic tools 2.

Clinical Features and Management

• Patients with lung cancer usually present with multiple symptoms, both respiratory related and constitutional 4.
• The initial evaluation of the patient with known or suspected lung cancer should include an assessment of symptoms, signs, and laboratory test results in a standardized manner as a screen for identifying those patients with paraneoplastic syndromes and a higher likelihood of metastatic disease 4.
• For most paraneoplastic syndromes, the best treatment is to treat the underlying malignancy, however, in many cases, treatment of moderate efficacy or urgent therapy is required 5.
• Specific recommendations for the management of the most common paraneoplastic syndromes, including cachexia, hypercalcemia, and hyponatremia, are provided 5.

Rare Cases and Importance of Early Diagnosis

• An overlap of two paraneoplastic syndromes secondary to lung cancer in a patient is very rare, as reported in a case of a 60-year-old male smoker who presented with dermatomyositis and Lambert-Eaton myasthenic syndrome secondary to lung squamous carcinoma 6.
• Recognition of paraneoplastic syndrome is crucial for early diagnosis of lung cancer because up to 80% of patients may present paraneoplastic syndromes before any other direct indication of malignancy 6.
• Early diagnosis and treatment of paraneoplastic syndrome is also important because delayed diagnosis may result in rapid disease progression and irreversible neurological damage 6.