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

New Treatment Options for Locally Advanced NSCLC

In This Article
Table of Contents

When lung cancer is categorized as "unresectable," your doctor is saying it is inoperable, which means that surgery is not an effective treatment for the cancer. Stage 3 non-small cell lung cancer (NSCLC) is usually considered unresectable 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 these are continually increasing survival rates.

doctor pointing to chest X-ray explaining to a female patient why her stage 3 lung cancer is unresectable (inoperable)
DragonImages / Getty Images

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, number of lymph nodes involved, and whether or how far the cancer has spread:

  • Stage 3A non-small cell lung cancer: This includes tumors that are large and have spread to nearby lymph nodes. It may also refer to tumors that are any size but have spread to lymph nodes that are further away but still on the same side of the body as the original cancer.
  • Stage 3B non-small cell lung cancer: This includes tumors of any size that have spread to distant lymph nodes or 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.

In general, stage 3A lung cancers may sometimes be treated with surgery while 3B is almost always deemed inoperable. Stage 3B lung cancer is often lumped together with stage 4 lung cancer into the category of "advanced lung cancer." Because advanced lung cancer is metastasized, which means it has spread to distant sites, tumors are too large or too numerous to be completely removed via surgery.

Causes

NSCLC is caused by a variety of factors, including:

  • Smoking: This is the leading cause of non-small cell lung cancer.
  • Secondhand smoke: Smoke exhaled by smokers, emitted from the lit end of a cigarette, pipe, or cigar, or from tobacco burning in a hookah, put you at risk.
  • Radon: The leading cause of NSCLC in non-smokers is radon exposure.
  • 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 more than one of these factors:

  • Location: Doctors may not be able to remove tumors too deep in the lung or located too close to a vital structure such as the heart.
  • General health: Pre-existing health conditions can put you at too high a risk for surgical complications such as reactions to anesthesia, excessive bleeding, blood clots, infections, or pneumonia.
  • Lung function: Removing 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. The process of reaching a diagnosis involves various tests and examinations:

  • Physical examination: Your doctor will check for unusual lung sounds, lymph node swelling, weight loss, and clubbing of the fingers.
  • Chest X-ray: This can show any masses in the lungs or enlarged lymph nodes.
  • Computed tomography (CT) scan: This three-dimensional image of the lungs provides more detail to check for masses.
  • 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): Doctors evaluate your lung capacity to determine if it would be dangerous to remove tissue, as doing so may strain lung capacity.
  • 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, doctors do sometimes perform surgery on patients with these lung cancers in an effort to reduce the severity of symptoms or improve the length and quality of life. Other treatments are used to better 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, which means it targets specific tumors in a specific location. Chemotherapy is a systemic treatment because it works to rid your entire body system of cancer (including cancerous cells that your doctor may not be able to see 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), plus VePesid or Etopophos (etoposide) given in four to six cycles.

A number of studies have looked at ways to improve the effectiveness of this combination, including adding in Alimta (pemetrexed) or Erbitux (cetuximab), adding more chemotherapy cycles, or increasing the dose of radiation. However, thus far, these approaches have not been found to improve survival.

This treatment will not cure cancer. However, it 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.

A common side effect of chemo drugs is neutropenia, low white blood cell count. This can predispose you to infections and may cause serious health concerns. Be sure to watch for signs of this problem and discuss them with your doctor.

Immunotherapy

Immunotherapy medications are treatments that boost your immune system so you can effectively fight cancer. Increasingly, these medications are offering durable responses—an oncology term that means people with advanced-stage lung cancer have a chance for long-term survival.

The immunotherapy drug Imfinzi (durvalumab) was approved specifically 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.

Targeted Therapy

Doctors can now make treatment more personal. Using molecular profiling (gene testing), they can determine if there are certain mutations in cancer cells. With this information, they will know if targeted therapy medications currently available for specific mutations can be used to stop mutated cancer cells from growing. 

Targeted therapy medications are available to manage EGFR mutationsALK rearrangements, and ROS1 rearrangements; other mutations are being studied in clinical trials. These treatments may be combined with other therapies to manage unresectable stage 3 lung cancer. 

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 poor.

The survival rate for stage 3B lung cancer with chemoradiation is less than 18 months. The median survival time is just over one year with treatment, and the five-year survival rate is only 3% to 7%.

For stage 3A lung cancer, survival rates are usually based on treatment options that include surgery. When surgery is not an option, the prognosis is likely to be similar to only slightly better than for stage 3B.

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 a poor 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 doctors who are leaders in the field and discussing your treatment with someone from a larger treatment facility where newer therapies are being used with success, if possible, 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 comprised of individuals with advanced stage disease.

A Word From Verywell

An unresectable lung cancer stage 3 diagnosis has historically been challenging to treat. Until recently, few advances in treatment have been made—this despite significant advances in the treatment of stage 4 NSCLC. Fortunately, this is changing with the addition of immunotherapy and targeted therapy.

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.

Was this page helpful?
Article Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. American Cancer Society. Non-small cell lung cancer stages. Updated October 1, 2019.

  2. American Cancer Society. Radon and Cancer. Updated September 23, 2015.

  3. Raaschou-Nielsen O, Andersen Z, Beelen R, Samoli E, Stafoggia M, Weinmayr G, et al. Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)Lancet Oncology. 2013;17(9)813-822. doi:10.1016/S1470-2045(13)70279-1

  4. Kanwal M, Ding XJ, Cao Y. Familial risk for lung cancerOncol Letters. 2017;13(2):535-42. doi:10.3892/ol.2016.5518

  5. Melosky B, Juergens R, McLeod D, et al. Immune checkpoint-inhibitors and chemoradiation in stage III unresectable non-small cell lung cancer. Lung Cancer. 2019. 134:259-267. doi:10.1016/j.lungcan.2019.05.027

  6. Kim YH, Ahn SJ, Kim YC, et al. Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiationJpn J Clin Oncol. 2016;46(2):144-51. doi:10.1093/jjco/hyv174

  7. Cheema PK, Rothenstein J, Melosky B, Brade A, Hirsh V. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Current Oncology. 2019. 26(1):37–42. doi:10.3747.co.25.4096

  8. American Cancer Society. Chemotherapy drugs used to treat NSCLC. Updated May 27, 2020.

  9. Lustberg MB. Management of neutropenia in cancer patientsClin Adv Hematol Oncol. 2012;10(12):825-6.

  10. Agustoni F, Hirsch FR. PACIFIC trial: new perspectives for immunotherapy in lung cancerTransl Lung Cancer Res. 2018;7(Suppl 1):S19–S24. doi:10.21037/tlcr.2017.12.12

  11. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. New England Journal of Medicine. 2017. 377(20):1919-1929. doi:10.1056/NEJMoa1709937

  12. NIH. National Cancer Institute. Non-small cell lung cancer treatment (PDQ®)–health professional version. Updated June 13, 2019.

  13. Lemjabbar-alaoui H, Hassan OU, Yang YW, Buchanan P. Lung cancer: Biology and treatment optionsBiochim Biophys Acta. 2015;1856(2):189-210. doi:10.1016/j.bbcan.2015.08.002