Is M1 small cell lung cancer (SCLC) considered metastatic or extensive locally advanced stage?

M1 Small Cell Lung Cancer is Considered Metastatic Disease

M1 small cell lung cancer (SCLC) is definitively classified as metastatic disease, which corresponds to extensive-stage SCLC in the traditional Veterans Administration Lung Cancer Study Group (VALSG) staging system. 1

TNM vs. VALSG Staging Systems

Small cell lung cancer can be staged using two different systems:

1. TNM Staging System (8th edition):

   • M1 disease is subdivided into three categories:
     • M1a: Satellite nodule(s) in the contralateral lung or malignant pleural/pericardial effusion
     • M1b: Single extrathoracic metastasis (including single non-regional lymph node)
     • M1c: Multiple extrathoracic metastases in one or more organs 1
   • Any M1 designation constitutes Stage IV disease

2. Modified VALSG Staging System:

   • Limited-stage (LS): Disease confined to a single hemithorax that can be encompassed in a single radiation port
   • Extensive-stage (ES): Disease beyond the boundaries of a single radiation port 1

Correlation Between TNM and VALSG Systems

In the combined TNM/VALSG approach for SCLC staging:

• M1 disease (all subcategories) corresponds to extensive-stage SCLC, with the following specific correlations:
  • M1a contralateral pleural effusion = ES-SCLC
  • M1a pericardial effusion = ES-SCLC
  • M1b (single extrathoracic metastasis) = ES-SCLC
  • M1c (multiple extrathoracic metastases) = ES-SCLC 1, 2

Clinical Implications

The distinction is critical for treatment planning and prognosis:

• Extensive-stage (M1) SCLC has significantly worse outcomes:

  • Median survival of 9-13 months 3, 4
  • 5-year survival rate of less than 5% without treatment 2
  • First-line treatment consists of platinum-etoposide chemotherapy plus immunotherapy (atezolizumab or durvalumab) 2, 3

• Limited-stage SCLC has better outcomes:

  • Median survival of 15-20 months
  • 5-year survival rate of 20-25% 2
  • Treatment typically involves concurrent chemoradiotherapy 2

Important Considerations

• M1 disease is always classified as extensive-stage, regardless of the specific M1 subcategory 1
• The presence of metastatic disease constitutes stage IV disease, and many patients with SCLC present with metastatic disease at diagnosis 1
• The treatment approach differs significantly between limited and extensive stage disease, with extensive (metastatic) disease requiring systemic therapy with less emphasis on local control 3, 4

Pitfalls to Avoid

• Do not confuse M1a ipsilateral pleural disease, which may still be considered limited-stage in some cases if it can be included in a single radiation port 1
• T3 and T4 tumors without distant metastases may be classified as either limited or extensive stage depending on whether they can be encompassed within a single radiation port 1
• Avoid misclassifying contralateral mediastinal lymph nodes, which are considered N3 disease but may still be limited-stage if they can be included in a radiation field 1

In summary, M1 SCLC is unequivocally classified as metastatic disease corresponding to extensive-stage SCLC, with important implications for treatment approach and prognosis.