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Non-Small Cell Lung Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment Option Overview for NSCLC

In NSCLC, results of standard treatment are poor except for the most localized cancers. All newly diagnosed patients with NSCLC are potential candidates for studies evaluating new forms of treatment.

Surgery is the most potentially curative therapeutic option for this disease. Postoperative chemotherapy may provide an additional benefit to patients with resected NSCLC. Radiation therapy combined with chemotherapy can produce a cure in a small number of patients and can provide palliation in most patients. Prophylactic cranial irradiation (PCI) may reduce the incidence of brain metastases, but there is no evidence of a survival benefit and the effect of PCI on quality of life is not known.[1,2] In patients with advanced-stage disease, chemotherapy or epidermal growth factor receptor (EGFR) kinase inhibitors offer modest improvements in median survival, though overall survival is poor.[3,4]

Chemotherapy has produced short-term improvement in disease-related symptoms in patients with advanced NSCLC. Several clinical trials have attempted to assess the impact of chemotherapy on tumor-related symptoms and quality of life. In total, these studies suggest that tumor-related symptoms may be controlled by chemotherapy without adversely affecting overall quality of life;[5,6] however, the impact of chemotherapy on quality of life requires more study. In general, medically fit elderly patients with good performance status obtain the same benefits from treatment as younger patients.

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.[7] In particular, genetic abnormalities in EGFR, MAPK, PI3K signaling pathways in subsets of NSCLC may define mechanisms of drug sensitivity and primary or acquired resistance to kinase inhibitors. EGFR mutations strongly predict the improved response rate and progression-free survival of inhibitors of EGFR. Fusions of ALK with EML4 genes form translocation products that occur in ranges from 3% to 7% in unselected NSCLC and are responsive to pharmacological inhibition of ALK by agents such as crizotinib. MET oncogene encodes hepatocyte growth factor receptor. Amplification of this gene has been associated with secondary resistance to EGFR tyrosine kinase inhibitors.

The standard treatment options for each stage of NSCLC are presented in Table 11.

Table 11. Standard Treatment Options for NSCLC

Stage (TNM Staging Criteria)Standard Treatment Options
Occult NSCLCSurgery
Stage 0 NSCLCSurgery
Endobronchial therapies
Stages IA and IB NSCLCSurgery
Radiation therapy
Stages IIA and IIB NSCLCSurgery
Neoadjuvant chemotherapy
Adjuvant chemotherapy
Radiation therapy
Stage IIIA NSCLCResected or resectable diseaseSurgery
Neoadjuvant therapy
Adjuvant therapy
Unresectable diseaseRadiation therapy
Chemoradiation therapy
Superior sulcus tumorsRadiation therapy alone
Radiation therapy and surgery
Concurrent chemotherapy with radiation therapy and surgery
Surgery alone (for selected patients)
Tumors that invade the chest wallSurgery
Surgery and radiation therapy
Radiation therapy alone
Chemotherapy combined with radiation therapy and/or surgery
Stage IIIB NSCLCSequential or concurrent chemotherapy and radiation therapy
Chemotherapy followed by surgery (for selected patients)
Radiation therapy alone
Stage IV NSCLCCytotoxic combination chemotherapy (first line)
Combination chemotherapy with bevacizumab or cetuximab
EGFR tyrosine kinase inhibitors (first line)
EML4-ALK inhibitors in patients with EML-ALK translocations
Maintenance therapy following first-line chemotherapy
Endobronchial laser therapy and/or brachytherapy (for obstructing lesions)
External-beam radiation therapy (primarily for palliation of local symptomatic tumor growth)
Recurrent NSCLCRadiation therapy (for palliation)
Chemotherapy or kinase inhibitors alone
EGFR inhibitors in patients with/without EGFR mutations
EML4-ALK inhibitors in patients with EML-ALK translocations
Surgical resection of isolated cerebral metastasis (for highly selected patients)
Laser therapy or interstitial radiation therapy (for endobronchial lesions)
Stereotactic radiation surgery (for highly selected patients)
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