Lung Cancer

Treatment Options by Stage

Choosing the best treatment plan for lung cancer can be challenging and requires the expertise of a multidisciplinary care team, who works together to determine the optimal treatment plan for your particular tumor. (You can learn more about the multidisciplinary care team here) Even once a plan has been established, it may change, depending on the results of staging procedures and other test results. For example, finding cancer cells in lymph nodes or in the surgical margins signals the need for additional treatment that may not have been originally planned, or determining that the function of the lungs or heart are poor may mean that certain types or surgery or radiation therapy cannot be used.

Making decisions about lung cancer treatment can be confusing because of all the different options and the factors that must be considered. You should talk openly with the members of your treatment team and ask questions about treatment options.

Lung cancer is difficult to control with the treatments that are currently available. For that reason, many doctors encourage people with lung cancer to consider participating in a clinical trial so that they have the opportunity to receive the newest and best treatments.

The options listed here by stage provide basic information about how your cancer may be treated. Many other details are involved in making treatment decisions, and your doctors will discuss these details with you.

NSCLC: Adenocarcinoma, Squamous Cell Carcinoma, Large Cell Carcinoma, and Mixtures of These Pathologic Types

Stage 0 (Carcinoma in Situ)

Stage 0 cancer is usually treated with surgery (removal of the tumor or a wedge or segmental resection). Additional treatment is not generally needed.

Stage I

Surgery is usually the primary treatment for stage IA or IB disease. Lymph nodes in the mediastinum must be removed or sampled during the surgery to ensure that the cancer has not spread. In most cases, no further therapy is given after the surgery, but if the risk for recurrence is high (the tumor is large, usually 4 cm (about 1½ inches) or more, adjuvant chemotherapy may be offered. It is difficult, however, to determine who is at highest risk for recurrence, and you should talk to your doctor about the risks and benefits of adjuvant treatment.

If the pathologist found cancer cells in the surgical margin of the normal tissue removed with the tumor, chemotherapy and/or radiation therapy may be given to destroy cancer cells that may remain. A second surgery is another option for removing remaining cancerous tissue.

Radiation therapy can be used to treat disease in people who are not surgical candidates, and SBRT is available at many treatment centers for these people.

Stage II

Treatment for stage II cancer depends on the location of the tumor. In general, surgery is the primary treatment. People who are not surgical candidates are often offered radiation therapy with or without chemotherapy. Chemotherapy after surgery is usually recommended for stage II disease because it improves overall survival. On rare occasions, neoadjuvant chemoradiation therapy or chemotherapy may be done to shrink a larger tumor so that it is easier to remove.

Stage IIIA

Treatment decision-making for stage IIIA cancer is complex and depends on many factors, including where the tumor is located, what tissues or structures it invades, whether cancer has spread to lymph nodes in the mediastinum and, if so, the number and size of the involved lymph nodes. If cancer is was not suspected in the mediastinal lymph nodes but the pathologist detects cancer cells in these nodes after a potentially curative operation, adjuvant therapy is recommended.

Chemotherapy, with or without radiation therapy, is often the first treatment given for stage IIIA cancer. If the response to treatment is good — that is, the tumor has shrunk and the involved lymph nodes become free of cancer — surgery (removal of part or all of the lung) may be done if the thoracic surgeon believes that the remaining cancer can be removed entirely; additional chemotherapy may then be given after surgery. If surgery is not considered to be an option, additional chemotherapy and/or radiation therapy may help to further shrink the tumor and reduce the risk of recurrence.

Concurrent chemotherapy and radiation therapy can be used with curative intent for people who are not surgical candidates. Adjuvant chemotherapy has been shown to improve survival for people in whom the cancer was thought to be stage I or II before cancer was found in mediastinal lymph nodes removed during surgery. It is not clear yet whether the addition of radiation therapy to chemotherapy is of benefit, and researchers are conducting studies to try to answer this question.

Stage IIIB

Surgery is not usually an option for stage IIIB cancer because the disease has spread too far to be completely removed. Treatment usually consists of concurrent chemoradiation therapy. In some centers, additional chemotherapy is given after radiation therapy has been completed. You may be able to choose a chemotherapy schedule; for example, some chemotherapy regimens may be given weekly, once every 3 weeks, or daily for a week every 4 weeks.

Stage IV

Stage IV (advanced) non-small cell lung cancer has been typically treated with chemotherapy, which cannot cure the cancer but can lengthen survival and improve the quality of life. Studies have shown that if the disease is stable after first-line chemotherapy, immediate second-line treatment with a different chemotherapy drug can improve the outcome. Surgery and radiation therapy are used in some instances to eliminate symptoms and improve the quality of life or to prevent debilitating complications.

Targeted therapy now offers an additional option for many people with advanced cancer. In order for targeted therapy to be used, however, genetic testing must be done on the tumor sample, and the results dictate which treatment can be used.

• If the tumor tests positively for the EGFR mutation, treatment with erlotinib or gefitinib is preferred as the initial therapy.
• If the tumor tests positively for the EML4-ALK fusion gene, treatment with crizotinib is recommended.
• If the tumor tests negatively for the EGFR mutation and EML4-ALK fusion gene, then a platinum-based chemotherapy combination is the standard for people who are healthy enough to tolerate the drugs. Patients who are not healthy enough may receive a single drug or palliative therapy with radiation therapy, surgery or other supportive measures. If the cancer is a type other than squamous cell carcinoma, bevacizumab added to the platinum-based chemotherapy is an option.
• Squamous cell carcinoma that tests negatively for the EGFR mutation may be treated with a platinum-based chemotherapy regimen that does not contain pemetrexed (because of the potential for excess side effects) or with another EGFR inhibitor, cetuximab, and chemotherapy.

Recurrent Disease After Surgery

In some instances, early stage cancer recurs (comes back). The recurrence may be at a local site in the chest or at a distant site outside the original lung cavity. If cancer recurs in or around the lungs and it is considered resectable, surgery may be done, followed by radiation therapy, with or without chemotherapy. If the recurrence includes lymph nodes in the mediastinum, concurrent chemoradiation therapy is an option. If the recurrence is outside the original lung cavity, the treatment choices are the same as the options for cancer that is stage IV at that time of diagnosis.

Metastatic Disease

Two of the most common sites of metastasis from lung cancer are the brain and bone.

BRAIN METASTASIS. Systemic chemotherapy may not be effective for brain metastasis because of the blood-brain barrier (a membrane that protects the brain by preventing substances in blood, such as drugs, from entering the brain). Therefore, local therapies are often used, and the choice of treatment depends on the number and location of the metastatic tumors. If there is a single metastatic site in the brain, surgery, followed by whole brain radiation, may be done. Another option is stereotactic radiosurgery (also known as GammaKnife or CyberKnife). This approach is usually used only when there are no more than three small metastatic tumors. Because the radiation is delivered precisely to the metastatic site, side effects are less likely to occur with stereotactic radiosurgery than with whole brain radiation therapy.

Whole brain radiation is usually the treatment of choice for people who have more than three metastatic brain tumors. Corticosteroids are usually given with the radiation to limit swelling in the brain; the drug may be discontinued after the treatment effects are over. If a person has had any type of seizure, medicines are given to prevent future seizures. Rarely, systemic chemotherapy or targeted therapy may be used because enough of the drug may cross the blood brain barrier to be effective. As an example, erlotinib, a targeted therapy drug, is sometimes effective for brain metastasis.

When brain metastases have been successfully treated, a MRI of the brain is often done as part of follow-up care.

Treatment of brain metastasis requires a discussion with all members of the multidisciplinary care team. Your team will talk to you about the benefits and risks of each treatment option in helping you to decide on the best choice for you.

BONE METASTASIS. The spread of cancer to bone can cause the loss of bone mass, a condition known as osteoporosis. This condition occurs when the bone cells that help rebuild bone (osteoblasts) don’t get replaced at the same rate as bone cells that naturally break down bone (osteoclasts). Bones become thin and porous (full of tiny holes) and are more likely to fracture (break) or cause pain and disability.

Radiation therapy can be used to help prevent or treat fractures, especially if the involved bone is a weight-bearing one. Radiation beams are targeted to the area of the metastasis and relief of symptoms is usually immediate and complete. If you have had a fracture or your doctor thinks you at high risk for fracture, orthopedic surgery may be done.

Treatment with a bisphosphonate is a standard option for bone metastasis. A bisphosphonate is a drug that prevents the loss of bone mass (it is typically used to treat osteoporosis). Another drug, denosumab (Xgeva) is a newer option; denosumab reduces the bone destruction that occurs with metastasis. Treatment with a bisphosphonate or denosumab will help to prevent bone fractures and can reduce the need for radiation therapy to alleviate bone pain. These medications are usually given with each cycle of chemotherapy and are sometimes given to maintain bone health in people who no longer need chemotherapy.

Small Cell Lung Cancer

Stage I-IIIB

Surgical resection followed by chemotherapy is often given with curative intent for stage I or IIA disease (although small cell lung cancer is rarely detected at this early stage). Concurrent chemoradiation therapy is typically given with curative intent to people who have stage I or IIA disease but are not surgical candidates or to people who have stage IIB, IIIA, or IIIB disease. If the cancer responds to treatment, radiation therapy to the brain is given to prevent relapse (return of cancer) in the brain and to prolong survival.

Stage IV

Chemotherapy is the primary treatment for stage IV disease or for earlier stage disease that recurs after initial therapy. If the tumor responds to therapy, radiation therapy to the brain is given to prevent relapse of disease in the brain and to prolong survival. Other types of radiation and surgical therapies may be used as palliative treatment, to relieve symptoms and to improve the quality of life (see Managing Symptoms).

Additional Sources of Information

• American Academy of Orthopaedic Surgeons: www.aaos.org
    Metastatic Bone Disease
• American Cancer Society: www.cancer.org
    Bone Metastasis Overview
• American Society of Clinical Oncology’s patient website: www.cancer.net
    What to Know: ASCO’s Guideline on Adjuvant Treatment for Lung Cancer (Decision Aids)
    What to Know: ASCO’s Guideline on Chemotherapy for Stage IV Non- small Cell Lung Cancer
• Lung Cancer Alliance: www.lungcanceralliance.org
    Understanding Brain Metastases: A Guide for Patient and Caregiver
• National Comprehensive Cancer Network: www.nccn.com
    NCCN Guidelines for Patients: Non-Small Cell Lung Cancer
    Treatment Summaries: Lung Cancer