What are the most common metastatic sites in women with primary lung cancer?

Most Common Metastatic Sites in Women with Primary Lung Cancer

In women with primary lung cancer, the most common metastatic sites are lymph nodes, liver, adrenal glands, bone, brain, and pleura, with women showing a notably higher propensity for nervous system metastases (43%) compared to men (35%). 1, 2, 3

Primary Metastatic Sites

The metastatic pattern in lung cancer follows a predictable hierarchy:

• Lymph nodes are among the most frequent sites of spread, though symptoms typically remain absent unless very bulky adenopathy develops 1, 2
• Bone metastases occur in 6-25% of patients at presentation, with vertebral bodies being the most common skeletal site, though any bone may be involved 1, 2
• Brain metastases are particularly common, with lung cancer accounting for approximately 70% of all cancers that initially present with symptomatic brain metastases 1, 2
• Liver metastases frequently occur and are often accompanied by weakness and weight loss, though liver function tests typically remain normal until very advanced stages 1, 2
• Adrenal gland metastases are typically asymptomatic and rarely cause adrenal insufficiency; these must be distinguished from benign adrenal adenomas which are common incidental findings 1, 2
• Pleural involvement commonly manifests as pleural effusion 1, 2

Sex-Specific Differences in Metastatic Patterns

Women demonstrate a significantly higher rate of nervous system metastases (43%) compared to men (35%), making brain imaging particularly important in female patients. 3

Younger patients also show increased propensity for nervous system involvement, which may be relevant given that women are increasingly diagnosed with lung cancer at younger ages. 3

Histology-Specific Patterns

The metastatic pattern varies by histologic subtype:

• Adenocarcinoma (the most common type in women) preferentially metastasizes to bone (39%) and the respiratory system (22%) 3
• Small cell lung cancer shows higher rates of liver (35%) and nervous system (47%) metastases 3

Clinical Presentation of Metastases

Systemic Symptoms

Patients with distant metastases often present with nonspecific symptoms including anorexia, weight loss, and fatigue, which are associated with worse prognosis even within the same cancer stage. 1, 2

Site-Specific Manifestations

• Bone metastases present with pain, bony tenderness, and possibly elevated serum calcium or alkaline phosphatase 1, 2
• Brain metastases may cause headache, nausea, vomiting, seizures, mental status changes, or may be completely asymptomatic 1, 2
• Liver metastases typically present with weakness and weight loss, but liver function tests remain normal until very advanced involvement 1, 2
• Lymph node metastases are usually clinically silent except with very bulky adenopathy 1, 2
• Adrenal metastases are typically asymptomatic 1, 2

Diagnostic Approach

For patients with systemic symptoms suggesting metastatic disease, biopsy of a metastatic site can efficiently establish both diagnosis and stage, as lymph nodes, liver, and adrenal glands are often readily amenable to biopsy. 1, 2

CT imaging with IV contrast is the preferred modality for detecting metastases in the chest, abdomen, and pelvis. 1, 2

Brain MRI is recommended for suspected brain metastases, with contrast increasing specificity for detection, especially for leptomeningeal spread. 2

PET/CT demonstrates higher sensitivity (92%) than bone scan (86%) for detecting bone metastases. 1, 2

Prognostic Implications

Median survival after diagnosis is 13 months for non-metastatic and 5 months for metastatic lung cancer. 3

Liver metastases confer the worst prognosis (3 months median survival), followed by bone metastases, whereas survival with respiratory and nervous system metastases is comparatively better. 3

Common Pitfalls

• Do not dismiss subtle neurologic symptoms in women with lung cancer, given their higher propensity for brain metastases 3
• Adrenal masses must be distinguished from benign adenomas, which are common incidental findings 1, 2
• Normal liver function tests do not exclude liver metastases, as these remain normal until very advanced stages 1, 2
• Bone pain with elevated calcium or alkaline phosphatase should prompt immediate evaluation for skeletal metastasis 1, 2