Non-small cell lung cancer


Non-small cell lung carcinoma
NSCLC Non-small cell lung cancer


Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small cell lung carcinoma (SCLC). It includes squamous cell carcinoma, adenocarcinoma and large cell carcinoma. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy is increasingly being used both pre-operatively (neoadjuvant chemotherapy) and post-operatively (adjuvant chemotherapy).


Early lung cancer may not cause any symptoms. Symptoms you should watch for include:

  • Chest pain
  • Cough that doesn't go away
  • Coughing up blood
  • Fatigue
  • Loss of appetite
  • Losing weight without trying
  • Shortness of breath
  • Wheezing

Other symptoms that may be due to NSCLC:

  • Bone pain or tenderness
  • Eyelid drooping
  • Hoarseness or changing voice
  • Joint pain
  • Nail problems
  • Swallowing difficulty
  • Swelling of the face
  • Weakness
  • Shoulder pain or weakness

Note: These symptoms can be due to other, less serious conditions. It is important to talk to your health care provider.


Smoking causes most cases of lung cancer. The risk depends on the number of cigarettes you smoke every day and for how long you have smoked. Being around the smoke from other people (secondhand smoke) also raises your risk for lung cancer. However, some people who do not smoke and have never smoked develop lung cancer.

Research shows that smoking marijuana may help cancer cells grow, but there is no direct link between the drug and developing lung cancer.

High levels of air pollution and drinking water containing high levels of arsenic can increase your risk for lung cancer. A history of radiation therapy to the lungs can also increase the risk.

Working with or near the following cancer-causing chemicals or materials can also increase your risk:

  • Asbestos
  • Chemicals such as uranium, beryllium, vinyl chloride, nickel chromates, coal products, mustard gas, chloromethyl ethers, gasoline, and diesel exhaust
  • Certain alloys, paints, pigments, and preservatives
  • Products using chloride and formaldehyde


If you smoke, stop smoking. It's never too late to quit. Your risk of lung cancer drops dramatically the first year after you quit. Stopping even after you've been diagnosed with early-stage lung cancer may improve your outlook.
Also avoid breathing in the smoke from other people's cigarettes, cigars, or pipes.
Routine lung cancer screening using chest x-ray or lung CT scan is not currently recommended for people who don't have symptoms. Many studies have been done to test the benefit of screening. Most experts have concluded that screening will not cure the disease or help people live longer. Screening may lead to many unneeded biopsies or surgeries.
The long-term use of vitamin C, vitamin E, and folate does not seem to reduce the risk of lung cancer.


The health care provider will perform a physical exam and ask questions about your medical history. You will be asked if you smoke, and if so, for how long you have smoked.

When listening to the chest with a stethoscope, the health care provider can sometimes hear fluid around the lungs, which could (but doesn't always) suggest cancer.

Tests that may be performed to diagnose lung cancer or see if it has spread include:

  • Bone scan
  • Chest x-ray
  • Complete blood count (CBC)
  • CT scan of the chest
  • MRI of the chest
  • Positron emission tomography (PET) scan
  • Sputum test to look for cancer cells
  • Thoracentesis (sampling of fluid build-up around the lung)

In some cases, the health care provider may need to remove a piece of tissue from your lungs for examination under a microscope. This is called a biopsy. There are several ways to do this:

Bronchoscopy combined with biopsy

  • CT-scan-directed needle biopsy
  • Endoscopic esophageal ultrasound (EUS) with biopsy
  • Mediastinoscopy with biopsy
  • Open lung biopsy
  • Pleural biopsy

If the biopsy shows that you do have lung cancer, more imaging tests will be done to determine the stage of the cancer. Stage means how big the tumor is and how far it has spread. Non-small cell lung cancer is divided into five stages:

  • Stage 0 - the cancer has not spread beyond the inner lining of the lung
  • Stage I - the cancer is small and hasn't spread to the lymph nodes
  • Stage II - the cancer has spread to some lymph nodes near the original tumor
  • Stage III - the cancer has spread to nearby tissue or to far away lymph nodes
  • Stage IV - the cancer has spread to other organs of the body, such as the other lung, brain, or liver


The outlook varies widely. Most often, NSCLC grows slowly. The cancer may spread to other parts of the body, including the bone, liver, small intestine, and brain.

However, in some cases, it can be very aggressive and cause rapid death. Chemotherapy has been shown to prolong the life and improve the quality of life in some patients with stage IV NSCLC.

Cure rates are related to the stage of disease and whether you are able to have surgery.

  • Stage I and II cancers have the highest survival and cure rates.
  • Stage III tumors can be cured in some cases.
  • Patients with stage IV disease or cancer that has returned are almost never cured. The goals of therapy are to extend and improve their quality of life.


  • Spread of disease beyond the lung
  • Side effects of surgery, chemotherapy, or radiation therapy


More than one kind of treatment is often used, depending on the stage of the cancer, the individual's overall health, age, response to chemotherapy, and other factors such as the likely side effects of the treatment. After full staging, the NSCLC patient can typically be classified in one of three different categories: patients with early, non-metastatic disease (Stage I, II and select III tumors), patients with locally advanced disease confined to the thoracic cavity (e.g., large tumors, tumors involving critical chest structures or patients with positive mediastinal lymph nodes) or patients with distant metastasis outside of the thoracic cavity.

Earyl/non-metastatic NSLC
NSCLCs are usually not very sensitive to chemotherapy and/or radiation, so surgery remains the treatment of choice if patients are diagnosed at an early stage. If patients have small, but inoperable tumors, they may undergo highly targeted, high intensity radiation therapy. New methods of giving radiation treatment allow doctors to be more accurate in treating lung cancers. This means less radiation affects nearby healthy tissues. New methods include Cyberknife and stereotactic body radiation therapy(SBRT). Certain patients deemed to be higher risk may also receive adjuvant (ancillary) chemotherapy after initial surgery or radiation therapy. There are a number of possible chemotherapy agents which can be selected however most will involve the platinum-based chemotherapy drug called cisplatin.

Other treatments are radiofrequency ablation and chemoembolization.

Advanced/metastatic NSCL
A wide variety of chemotherapies options exist for used in advanced (metastatic) NSCLC. These agents include both traditional chemotherapies like cisplatin which indiscriminately target all rapidly dividing cells as well as newer targeted agents which are more tailored to specific genetic aberrations found within a patient's tumor. At present there are two genetic markers which are routinely profiled in NSCLC tumors to guide further treatment decision making: mutations within EGFR and Anaplastic Lymphoma Kinase. There are also a number of additional genetic markers which are known to be mutated within NSCLC and may impact treatment in the future, including BRAF (gene), HER2/neu and KRAS.

Roughly 10-35% of NSCLC patients will have drug sensitizing mutations of the EGFR. The distribution of these mutations have been found to be race-dependent, with one study estimating that 10% of Caucasians but 50% of Asians will be found to have such tumor markers. A number of different EGFR mutations have been discovered, however certain aberrations will result in hyperactive forms of the protein. Patients with these mutations are more likely to have adenocarcinoma histology and be non-smokers or light smokers. These patients have been shown to be sensitized to certain medications which block the EGFR protein known as tyrosine kinase inhibitors specifically, erlotinib, gefitinib or afatinib.

ALK gene rearrangements
Up to 7% of NSCLC patients have EML4-ALK translocations or mutations in the ROS1 gene; these patients may benefit from ALK inhibitors which are now approved for this subset of patients. Crizotinib gained FDA approval in August 2011 and is an inhibitor of several kinases, specifically ALK, ROS1 and MET. Crizotinib has been shown in clinical studies to have response rates of ~60% if patients are shown to have ALK positive disease. Several studies have also shown that ALK mutations and EGFR activating mutations are typically mutually exclusive. Thus, it is not recommended for patients who fail crizotinib to be switched to an EGFR-targeted drug such as erlotinib.

Other treatment options
NSCLC patients with advanced disease who are not found to have either EGFR or AKT mutations may receive bevacizumab which is a monoclonal antibody medication targeted against the vascular endothelial growth factor (VEGF). This is based on an Eastern Cooperative Oncology Group study which found that adding bevacizumab to carboplatin and paclitaxel chemotherapy for certain patients with recurrent or advanced non-small-cell lung cancer (stage IIIB or IV) may increase both overall survival and progression free survival. The FDA also recently approved the anti-PD-1 agent nivolumab for advanced or metastatic squamous cell carcinoma.

 Approved therapies:
 Targeted therapy drugs are often used in combination with chemotherapy drugs:

  • Afatinib (Gilotrif)
  • Bevacizumab (Avastin)
  • Ceritinib (Zykadia)
  • Crizotinib (Xalkori)
  • Erlotinib (Tarceva)
  • Nivolumab (Opdivo)
  • Ramucirumab (Cyramza)
  • Pembroliyumab (Keytruda)- FDA approved in metastatic NSCLC for first-line therapy

Some targeted therapies only work in people whose cancer cells have certain genetic mutations. Your cancer cells will need to be tested in a laboratory to see if these drugs might help you.