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Non-Small Cell Lung Cancer (NSCLC)

Practice Essentials

Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Histologically, NSCLC is divided into adenocarcinoma, squamous cell carcinoma (SCC) (see the image below), and large cell carcinoma. Patients with NSCLC require a complete staging workup to evaluate the extent of disease, because stage plays a major role in determining the choice of treatment.

Non–small cell lung cancer. A cavitating right low

Non–small cell lung cancer. A cavitating right lower lobe squamous cell carcinoma.

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See the Critical Images slideshow Cutaneous Clues to Diagnosing Metastatic Cancer to help identify various skin lesions that are cause for concern. 

Go to Small Cell Lung Cancer for complete information on this topic. Go to Oncology Decision Point for expert commentary on NSCLC treatment decisions and related guidelines.

Signs and symptoms

NSCLC is often insidious, producing no symptoms until the disease is well advanced. Early recognition of symptoms may be beneficial to outcome.

At initial diagnosis, 20% of patients have localized disease, 25% of patients have regional metastasis, and 55% of patients have distant spread of disease. Symptoms depend on the location of cancer.

The most common signs and symptoms of lung cancer include the following:

Cough

Chest pain

Shortness of breath

Coughing up blood

Wheezing

Hoarseness

Recurring infections such as bronchitis and pneumonia

Weight loss and loss of appetite

Fatigue

Metastatic signs and symptoms may include the following:

Bone pain

Spinal cord impingement

Neurologic problems such as headache, weakness or numbness of limbs, dizziness, and seizures

See Presentation for more detail.

Diagnosis

Testing

After physical examination and CBC, chest x-ray is often the first test performed. Chest radiographs may show the following:

Pulmonary nodule, mass, or infiltrate

Mediastinal widening

Atelectasis

Hilar enlargement

Pleural effusion

There are several methods of confirming diagnosis, with the choice determined partly by lesion location. These methods include the following:

Bronchoscopy

Sputum cytology

Mediastinoscopy

Thoracentesis

Thoracoscopy

Transthoracic needle biopsy (CT- or fluoroscopy-guided)

Staging

A chest CT scan is the standard for staging lung cancer. The TNM (tumor-node-metastasis) staging system from the American Joint Committee for Cancer Staging and End Results Reporting is used for all lung carcinomas except small-cell lung cancer. The TNM takes into account the following key pieces of information:

T describes the size of the primary tumor

N describes the spread of cancer to regional lymph nodes

M indicates whether the cancer has metastasized

Primary tumor (T) involvement is as follows:

Tx – Primary tumor cannot be assessed

T0 – No evidence of tumor

Tis – Carcinoma in situ

T1, T2, T3, T4: size and/or extension of the primary tumor

Lymph node (N) involvement is as follows:

Nx – Regional nodes cannot be assessed

N0 – No regional node metastasis

N1 – Metastasis in ipsilateral peribronchial and/or ipsilateral hilar nodes and intrapulmonary nodes, including involvement by direct extension

N2 – Metastasis in ipsilateral mediastinal and/or subcarinal node

N3 – Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene node, or supraclavicular node

Metastatic (M) involvement is as follows:

M0 – No metastasis

M1 – Distant metastasis

Positive pleural effusion is stage 4

See Workup for more detail. See also Lung Cancer Staging — Radiologic Options, a Critical Images slideshow, to help identify stages of the disease process.

Management

Surgery, systemic therapy, and radiation are the main treatment options for NSCLC. Because most lung cancers cannot be cured with currently available therapeutic modalities, the appropriate application of skilled palliative care is an important part of the treatment of patients with NSCLC.

Surgery

Surgery is the treatment of choice for stage I and stage II NSCLC. Several different types of surgery can be used, as follows:

Lobectomy – removing a section of the lung

Pneumonectomy – removing the entire lung

Wedge resection – removing part of a lobe

Systemic therapy

Approximately 80% of all patients with lung cancer are considered for systemic therapy at some point during the course of their illness. Multiple randomized, controlled trials and large meta-analyses all confirm the superiority of combination chemotherapy regimens up front for advanced NSCLC.

The American Society for Clinical Oncology (ASCO) guidelines recommend that first-line treatment for NSCLC include a platinum combination. In younger patients, with a good performance status or in the adjuvant setting, cisplatin is preferred, but in older patients or those with significant comorbidities, carboplatin may be substituted.

Use of agents targeted to specific molecular features of the tumor has become standard practice. Depending on the molecular features, recommended systemic therapy regimens may include combinations of targeted agents with chemotherapy, or targeted agents alone.

Radiation

In the treatment of stage I and stage II NSCLC, radiation therapy alone is considered only when surgical resection is not possible.
 Stereotactic radiation is a reasonable option for lung cancer treatment among those who are not candidates for surgery.
Beta blockers have been found to improve overall survival, disease-free survival, and distant metastasis–free survival, though not locoregional progession–free survival, in patients with NSCLC undergoing radiotherapy.

See Treatment for more detail. 

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