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NON-SMALL CELL LUNG CANCER OVERVIEW — Non-small cell lung cancer (NSCLC) accounts for between 85 and 90 percent of all lung cancers; the remaining 10 to 15 percent are small cell lung cancers. This distinction is important when considering treatment.
This article will discuss the treatment of NSCLC confined to the chest (stage I, stage II, and stage III disease). The treatment of NSCLC that has spread more widely (stage IV) is discussed separately. The risks, symptoms, and diagnosis of NSCLC are also discussed separately. (See "Patient education: Non-small cell lung cancer treatment; stage IV cancer (Beyond the Basics)" and "Patient education: Lung cancer risks, symptoms, and diagnosis (Beyond the Basics)".)
More detailed information about lung cancer, written for healthcare providers, is available by subscription. (See 'Professional-level information' below.)
CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.
In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.
STAGING OF NON-SMALL CELL LUNG CANCER — Once lung cancer is diagnosed, the next step is to review its size, determine its exact location, and find out if it has spread. This process is called staging. Determining the stage of a lung cancer can be complicated because many features of the tumor are factored in at the same time. The stage of non-small cell lung cancer (NSCLC) is based on:
●The size and location of the tumor
●Whether the tumor has spread to lymph nodes and tissues inside the chest
●Whether the tumor has spread to places outside the chest (for example, lung cancer can spread, or "metastasize," to places like the lymph nodes, adrenal glands, or elsewhere)
NSCLC stages range from I to IV, with the divisions developed to provide some guide to prognosis as well as to help define the most appropriate treatment approach. In general, the lower numbers (stages I and II) suggest that the tumor is smaller and has not spread far; these characteristics are associated with a more favorable prognosis. By comparison, the higher numbers (stage III and IV) suggest that the tumor is larger or has metastasized, features associated with a more limited prognosis.
●Stage I – Stage I means that the tumor is smaller than or equal to 3 cm (about 1.2 inches) in maximum diameter and has not spread to any other tissues or lymph nodes (figure 1).
●Stage II – Stage II means that the tumor is between 3 and 7 cm (between about 1.2 to 3 inches) in size, has spread to the lymph nodes, has invaded the tissues surrounding the lung, or has started to invade the large bronchial tubes (figure 2).
●Stage IIIA – Stage IIIA disease means that the tumor is bigger than 7 cm (about 3 inches), has spread to the lymph nodes in the center of the chest (called the mediastinum), or has spread to the rib cage, heart, esophagus, or trachea (figure 3).
●Stage IIIB – Stage IIIB disease means that the tumor has spread to lymph nodes on the other side of the mediastinum, or lymph nodes above or behind the clavicle (collar bone). Stage IIIB also includes large tumors that have spread to the rib cage, heart, esophagus (swallowing tube), or trachea with involvement of the mediastinal lymph nodes (figure 4).
●Stage IV – Stage IV means that the cancer has spread (metastasized) to the other side of the chest or to tissues outside of the chest, or has caused a "malignant effusion." A malignant effusion is a collection of fluid containing cancer cells that may accumulate between the outside of the lung and the inner wall of the chest (pleural effusion) or within a contained space around the heart (pericardial effusion) (figure 5). (See "Patient education: Non-small cell lung cancer treatment; stage IV cancer (Beyond the Basics)".)
Stage I to III NSCLCs are referred to as localized cancers, while stage IV is called advanced cancer.
IMPORTANCE OF SMOKING CESSATION — The importance of quitting smoking cannot be overemphasized. People who continue to smoke do not do as well as those who quit. One reason is that if they survive their first lung cancer, they have a substantial chance of developing a second lung cancer because of continued smoking. Furthermore, because treatment with chemotherapy, radiation therapy, and surgery can cause further lung damage, it is important to have the best lung function possible prior to and after receiving treatment. Thus, if at all possible, patients should stop smoking. (See "Patient education: Quitting smoking (Beyond the Basics)".)
This is also an important opportunity for family and friends to stop smoking. There are inherited genetic factors that increase the likelihood of getting lung cancer, especially if a person with these genetic factors smokes or is around those who do.
STAGE I AND II TREATMENT — Surgery is the historical gold standard that is most commonly recommended as the first treatment in people with stage I or II non-small cell lung cancer (NSCLC). Radiation therapy may be recommended for people who are not good candidates for surgery due to severe lung disease or other underlying medical problems, and some research is now exploring whether radiation may be an appropriate substitute for surgery in patients who may still be candidates for surgery. In some cases, the initial surgery or radiation therapy may be followed by adjuvant (after surgery) chemotherapy.
Surgery — Surgery to remove the cancer is the preferred treatment for stage I and stage II NSCLC. Options for surgery include the following, depending upon the size and position of the tumor in the chest:
●Lobectomy – This is the removal of one lobe (section) of the lung. (Normally the right lung has three lobes, and the left lung has two.)
●Segmentectomy or wedge resection – Both of these procedures involve removing part of the lung but not an entire lobe. They may be considered in some patients with a small tumor of 2 cm or smaller. This form of surgery may also be preferred for some people who could not tolerate conventional lobectomy, for example, in the case of a person whose lungs do not work well.
●Pneumonectomy – This is the removal of the entire affected lung. It is sometimes necessary in cases where lobectomy cannot completely remove the tumor, as is often the case for a primary tumor near the middle of the chest. Pneumonectomy requires that the remaining lung be relatively healthy.
In some cases, a person who is thought to have stage I or II NSCLC has surgery, which reveals that the disease has spread to the mediastinal lymph nodes. If this happens, the person’s cancer is reclassified as stage III. This is referred to as "up-staging." Because postoperative staging includes evaluation of findings from tissue under the microscope, this "pathologic staging" is more precise than "clinical staging" that is based on the findings of imaging studies alone. (See 'Stage III treatment' below.)
Radiation therapy — Radiation therapy involves the use of X-rays to destroy cancer cells. Radiation therapy may be recommended for people with stage I or II NSCLC in the following situations:
●After surgery, radiation therapy may be recommended for patients with tumor left behind at the margins (edges) of the surgical resection, or for patients felt to have a high risk for locoregional (nearby) recurrence. It is not a clear standard therapy, and it is not indicated in patients with no lymph node involvement who have negative surgical margins (no evidence of cancer at the margins), with some evidence suggesting that it can have a net harmful effect in such patients.
●Radiation therapy may be used, alone or with chemotherapy, in people who are unable to tolerate or do not want surgery.
Radiation treatments are brief and not painful, similar to having an X-ray. Treatments are usually done five days per week for several weeks.
A different technique to give radiation, called stereotactic body radiation therapy (SBRT) or sometimes referred to as stereotactic ablative body radiation (SABR), involves giving more radiation to a small area over a few daily treatments (five or fewer). Studies of SBRT demonstrate very promising disease outcomes in patients with node-negative tumors, and mounting evidence supports its use as an alternative effective treatment strategy for patients with serious medical issues that make them a poor candidate for lung surgery. There is growing interest in the use of SBRT for patients who are potential candidates for surgery but wish to avoid it. Long-term efficacy and side effects for this relatively new approach compared with conventional surgery remains unclear.
Radiation side effects — Radiation therapy can cause side effects during treatment. Side effects usually resolve after treatment ends. The most common side effects of radiation therapy for lung cancer are:
●Difficulty swallowing due to swelling and irritation of the esophagus (called esophagitis)
●Swelling and irritation of the normal lung surrounding the tumor (called pneumonitis)
●Fatigue
●Skin irritation in the area being treated; this can look like a sunburn on the chest
●Hair loss just in the area being treated
Adjuvant chemotherapy — Chemotherapy is a treatment given to slow or stop the growth of cancer cells. Even after a cancer has been removed with surgery, cancer cells can remain in the body, increasing the risk of a relapse.
Chemotherapy can get rid of these cancer cells and increase the chance of cure, but it is indicated only in patients with a high enough risk of recurrence to justify the side effects of chemotherapy. Chemotherapy in the postoperative setting (after surgery) is called adjuvant (meaning "helper") therapy. It is typically recommended for people with stage II or III NSCLC, and for some (but not all) people with stage I disease, as it is generally not recommended for patients with node-negative cancers that measure 4 cm in diameter or smaller. These general guidelines may be individualized based on the specific features of the cancer and the health and preferences of the patient.
Chemotherapy is not given every day but instead is given in cycles. A cycle of chemotherapy, which is typically 21 or 28 days, refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines. Most treatments involve a combination of two chemotherapy drugs (called a doublet chemotherapy regimen). The best studied combinations include the agent cisplatin, though the potential for challenging side effects may make it a less ideal choice than the related drug carboplatin for some patients. Most of the drugs are given into a vein (intravenous or "IV"). Typically, adjuvant treatment regimens for NSCLC last about three months. (See "Patient education: Non-small cell lung cancer treatment; stage IV cancer (Beyond the Basics)", section on 'Chemotherapy'.)
Your healthcare provider can describe which specific chemotherapy drugs will be recommended.
Side effects — The most common side effects of chemotherapy used for NSCLC include:
●A lowered white blood cell count (which can increase the risk of infection) – Chemotherapy is associated with a 1 to 2 percent risk of fatal infections.
●Fever related to a low white blood cell count.
●Nausea and vomiting.
●Bowel changes, which may include constipation or diarrhea.
Other side effects may occur, and these vary with the exact regimen of therapy being administered. Fortunately, the common side effects of chemotherapy are, with rare exception, only temporary.
Adjuvant targeted therapy — In select situations, people with cancers that have a mutation in a gene called "epidermal growth factor receptor" (EGFR) may benefit from a drug called osimertinib. This drug is a type of "targeted therapy;" it targets the EGFR gene, blocking growth of cancer cells. Osimertinib can cause decreases in blood counts, gastrointestinal symptoms (like pain, nausea, or diarrhea), and in rare cases, can affect the heart. Side effects go away when the drug is stopped.
Adjuvant immunotherapy — Immunotherapy, a type of treatment that uses the body's immune system to help slow or stop cancer growth, is a newer option that may be offered in some situations after surgery. This may be an option for certain people, particularly those whose cancers have a protein called "programmed cell death ligand 1" (PD-L1) on the surface of their cells.
STAGE III TREATMENT — There is no one "best" treatment for people with stage III non-small cell lung cancer (NSCLC). Treatment depends upon the size and location of the tumor, lymph node involvement, and whether surgery has already been done. Recommendations should be individualized by a multi-specialty team; decisions regarding treatment approach should be based on the features of the cancer and the person’s individual needs, underlying health, and preferences.
The options generally include some combination of the following:
●Radiation therapy (see 'Radiation therapy' above)
●Chemotherapy (see 'Adjuvant chemotherapy' above)
●Surgery (see 'Surgery' above)
In many people with stage III NSCLC, a combination of chemotherapy and radiation therapy is recommended as the cornerstone of treatment. In some cases, initial treatment consists of chemotherapy or chemotherapy with radiation (this is called chemoradiotherapy), followed by surgery. Chemotherapy and radiation therapy may be given together (called concurrent chemoradiotherapy) or one treatment after the other (called sequential chemoradiotherapy). In some cases, surgery may be the initial step, particularly when unsuspected lymph node disease is found for what was originally thought to be stage I or II disease. If this occurs, surgery is generally followed by chemotherapy and less commonly, radiation. (See 'Adjuvant chemotherapy' above.)
In select situations, additional treatments may be offered:
●Osimertinib, for those with epidermal growth factor receptor (EGFR)-mutant stage IIIA disease. (See 'Adjuvant targeted therapy' above.)
●Immunotherapy, for people whose cancers have certain characteristics. (See 'Adjuvant immunotherapy' above.)
An immunotherapy drug may be considered in some situations following concurrent chemoradiotherapy for stage III NSCLC. Immunotherapy has been shown to improve survival in patients eligible for immunotherapy who have completed concurrent chemoradiotherapy for unresectable stage III NSCLC. (See 'Adjuvant immunotherapy' above.)
PANCOAST TUMORS — The term Pancoast tumor (also called superior sulcus tumor) refers to a non-small cell lung cancer that is located in the top part of one of the lungs, in a region called the superior sulcus. Pancoast tumors can involve nerves, causing a unique set of symptoms referred to as Pancoast syndrome.
Initially, symptoms may include shoulder or arm pain, weakness of the muscles of the hand, and flushing or excessive sweating on one side of the face. As the tumor progresses, the flushing can disappear, the eyelid may droop, and the involved side may not sweat.
As long as there is no evidence of distant spread, treatment of Pancoast tumors usually consists of a combination of chemotherapy and radiation, potentially followed by surgery, as long as there is no evidence of distant spread.
CLINICAL TRIALS — Progress in treating lung cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Whenever possible, patients with lung cancer are encouraged to enroll in a clinical trial. Ask for more information about clinical trials, or read about clinical trials at:
●www.cancer.gov/clinicaltrials/
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (http://www.cancer.net/pre-act).
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient-level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Non-small cell lung cancer (The Basics)
Patient education: Lung cancer (The Basics)
Patient education: Lung cancer screening (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient education: Non-small cell lung cancer treatment; stage IV cancer (Beyond the Basics)
Patient education: Lung cancer risks, symptoms, and diagnosis (Beyond the Basics)
Patient education: Small cell lung cancer treatment (Beyond the Basics)
Professional-level information — Professional-level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional-level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Overview of the initial treatment and prognosis of lung cancer
Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer
Pathology of lung malignancies
Management of stage I and stage II non-small cell lung cancer
Management of stage III non-small cell lung cancer
Systemic therapy in resectable non-small cell lung cancer
Superior pulmonary sulcus (Pancoast) tumors
The following organizations also provide reliable health information.
●The National Library of Medicine
(www.nlm.nih.gov/medlineplus/lungcancer.html)
●American Society of Clinical Oncology
●Global Resource for Advancing Cancer Education (GRACE)
●Lung Cancer Alliance
