What Is Unresectable Stage 3 Non-Small Cell Lung Cancer?

Stage 3 non-small cell lung cancer (NSCLC) is usually considered unresectable (inoperable) if the cancer is too widespread or if the tumors are located in areas that can't be reached via surgery.

You may be shaken by the thought of inoperable cancer, but keep in mind that unresectable does not mean untreatable. Newer medications and therapies have made it easier to manage NSCLC, and treatments are increasing survival rates.

Types of Unresectable Stage 3 NSCLC

Stage 3 non-small cell lung cancer, considered locally advanced lung cancer, is broken down into two different designations based on the size of the tumor, lymph node involvement, and how far it has metastasized (spread):

• Stage 3A non-small cell lung cancer: This includes tumors up to five centimeters (cm) and have spread to lymph nodes on the same side of the body as the original cancer.
• Stage 3B non-small cell lung cancer: This includes tumors up to seven cm an have invaded structures in the chest, such as the heart and esophagus. These tumors have not spread to distant regions such as the brain, bones, liver, or adrenal glands.
• Stage 3B non-small cell lung cancer: This includes tumors that can measure greater than 7 cm and have invaded the chest, as well as lymph nodes on either side of the body.

Causes

NSCLC is caused by a variety of factors, including:

• Smoking: This is the leading cause of non-small cell lung cancer.
• Radon: The leading cause of NSCLC in non-smokers is radon exposure.
• Secondhand smoke: Smoke exhaled by smokers, emitted from the lit end of a cigarette, pipe, cigar, or from tobacco burning in a hookah, put you at risk.
• Air pollution: Pollution is responsible for an estimated 15% of worldwide lung cancer deaths.
• Genetics: Approximately 8% of lung cancers are hereditary or related to a genetic predisposition.

Tumors that continue to grow and spread can develop into advanced lung cancer. NSCLC that is not diagnosed early is more likely to become non-resectable.

Lung cancer may be considered unresectable due to one or a combination of factors:

• Location: Healthcare providers may not be able to remove tumors that are located deep in the lung or too close to a vital structure, such as the heart.
• General health: Pre-existing health conditions can put you at high risk for surgical complications such as reactions to anesthesia, excessive bleeding, blood clots, infections, or pneumonia.
• Lung function: Removal of your lung tissue can worsen conditions such as chronic obstructive lung disease (COPD) or other lung diseases.

Diagnosis

Roughly 20% of all people with lung cancer find out they have unresectable stage 3 NSCLC at the time of diagnosis.

Diagnosis involves various tests and examinations:

• Physical examination: Your healthcare provider will check for unusual lung sounds, lymph node swelling, weight loss, and clubbing of the fingers.
• Chest X-ray: This test can identify masses in the lungs or enlarged lymph nodes.
• Computed tomography (CT) scan: This three-dimensional image of the lungs provides more detail than an X-ray.
• Positron emission tomography (PET)/CT scan: A PET scan combined with a CT scan can help diagnose cancer and detect metastases to the liver, bones, adrenal glands, or other organs.
• Magnetic resonance imaging (MRI) scan: This provides two- or three-dimensional images of soft tissues and is often used to look for possible spread of lung cancer to the brain or spinal cord.
  
• Lung tissue biopsy: A sample of lung tissue is taken using a special needle or a scope and then analyzed under a microscope.
• Pulmonary function tests (PFTs): Healthcare providers evaluate your lung capacity to assess whether your lung cancer (or another lung disease) has affected your breathing and whether your lungs can continue to function after lung tissue is removed.
• Blood tests: This may include a liquid biopsy, which can provide information about genetic mutations and characteristics of your cancer.

The results of these tests can determine the stage of your cancer.

Treatment Options

While unresectable stage 3 lung cancer is said to be inoperable, sometimes surgery can help reduce the severity of symptoms or improve the length and quality of life even if the whole tumor can't be surgically removed. Other treatments are used to help manage the disease. Often, the most effective treatments include a combination of therapies.

Chemotherapy and Radiation

For many people with stage 3 non-small cell lung cancer, a combination of chemotherapy and radiation therapy offers the best outcomes.

Radiation is a local therapy that is directed to target specific tumors. Chemotherapy is a systemic treatment because it works to rid your entire body system of cancer (including cancerous cells that may not be visible on scans).

The two treatments are usually given at the same time. This combination therapy appears to improve survival more than if chemotherapy and radiation are used sequentially (one after the other).

Chemotherapy for lung cancer most commonly involves using a combination of a platinum drug, such as Platinol (cisplatin) or Paraplatin (carboplatin), combined with either Pemetrexed or Paclitaxel. You may receive 2-4 cycles of chemotherapy with radiation, then immunotherapy.

The treatment for stage 3 NSCLC doesn't always cure cancer, but it can be curative. And even when it isn't a cure, treatment can allow you to enjoy a longer life. Side effects of chemotherapy are less problematic than they were for previous generations, so you should also be able to have a better quality of life than you would experience if you opted not to have any treatment for advanced-stage cancer.

Immunotherapy

Immunotherapy medications are treatments that boost your immune system so you can effectively fight cancer. Increasingly, these medications are offering durable responses—even offering a high chance of long-term survival with advanced-stage lung cancer.

The immunotherapy drug Imfinzi (durvalumab) is approved for the treatment of inoperable stage 3 NSCLC. When this drug is used after chemotherapy and radiation therapy, it has been shown to improve progression-free survival—the amount of time during which people were alive and their tumor did not progress.

In studies, the progression-free survival was 17.2 months for people treated with Imfinzi and 5.6 months for those treated with a placebo. There was also a significant improvement in the median time it took for cancer to metastasize. Overall survival was also longer for those treated with Imfinzi, with a two-year survival rate of 66.3% versus 55.6% for the placebo group.

Fortunately, these improvements seem to come without major side effects in most people. When they do occur, common side effects of immunotherapy medications include inflammation of the lungs and other regions of the body.

Targeted Therapy

Using molecular profiling (gene testing), your healthcare providers can determine if your tumor has certain mutations in your cancer cells. With this information, your healthcare providers will know if you could improve with targeted therapy medications that are used to treat tumors that have specific mutations. 

Targeted therapy medications are available to manage EGFR mutations, ALK rearrangements, ROS1 rearrangements, the KRAS G12C mutation, and other rare genetic alterations. Examples include drugs such as Krazati (adagrasib), Lumakras (sotorasib), Rybrevant (amivantamab-vmjw), and Tagrisso (osimertinib).

Prognosis

The success of newer treatments and the effective use of chemoradiation certainly offer some hope. That said, the prognosis for inoperable stage 3 lung cancer is still not good.

Coping

Advances in the treatment of lung cancer now provide more options, but along with this comes the need for you to weigh the potential risks and benefits of different treatments.

Between the many decisions you need to make and the feelings of discouragement that may come with your prognosis, you may feel overwhelmed. Taking the time to research your specific type of cancer can help you to feel more in control and able to make the best decision.

Seeking out healthcare providers who are experienced in treating lung cancer and considering newer or experimental therapies can also offer some peace of mind to help you move forward.

You may also find it helpful to join a lung cancer support group so you can get support and connect with others who are also living with advanced-stage lung cancer.

A Word From Verywell

An unresectable lung cancer stage 3 diagnosis is challenging for you and your loved ones. Fortunately, treatments are advancing.

Being your own advocate can help you ensure that you're able to take advantage of the newest treatments that may offer better outcomes and fewer adverse side effects. Don't be afraid to ask questions and get a second opinion as you work to meet your goals for treatment and the best quality of life possible.