Before a patient begins lung cancer treatment, an experienced lung cancer pathologist must review the pathologic material. This is critical because SCLC, which responds well to chemotherapy and is generally not treated surgically, can be confused on microscopic examination with NSCLC. Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but most lung tumors can be classified by light microscopic criteria.
(Refer to the Staging Evaluation section of this summary for more information on tests and procedures used for staging.)
The identification of mutations in lung cancer has led to the development of molecularly targeted therapy to improve the survival of subsets of patients with metastatic disease. In particular, subsets of adenocarcinoma now can be defined by specific mutations in genes encoding components of the epidermal growth factor receptor (EGFR) and downstream mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinases (PI3K) signaling pathways. These mutations may define mechanisms of drug sensitivity and primary or acquired resistance to kinase inhibitors.
Other genetic abnormalities of potential relevance to treatment decisions include translocations involving the anaplastic lymphoma kinase (ALK)-tyrosine kinase receptor, which are sensitive to ALK inhibitors, and amplification of MET (mesenchymal epithelial transition factor), which encodes the hepatocyte growth factor receptor. MET amplification has been associated with secondary resistance to EGFR tyrosine kinase inhibitors.
Multiple studies have attempted to identify the prognostic importance of a variety of clinicopathologic factors.[6,15,16,17,18] Factors that have correlated with adverse prognosis include the following:
- Presence of pulmonary symptoms.
- Large tumor size (>3 cm).
- Nonsquamous histology.
- Metastases to multiple lymph nodes within a TNM-defined nodal station.[19,20,21,22,23,24,25,26,27,28,29] (Refer to the Evaluation of Mediastinal Lymph Node Metastasis section of this summary for more information.)
- Vascular invasion.[16,30,31,32]
For patients with inoperable disease, prognosis is adversely affected by poor performance status and weight loss of more than 10%. These patients have been excluded from clinical trials evaluating aggressive multimodality interventions.
In multiple retrospective analyses of clinical trial data, advanced age alone has not been shown to influence response or survival with therapy.