Patient information: Non-small cell lung cancer treatment; early stage (stage I and II) cancer

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 early stage non-small cell lung cancer (stage I and stage II disease). The treatment of locally advanced (stage III) and advanced unresectable, metastatic (stage IV), and recurrent non-small cell lung cancer are discussed separately. (See "Patient information: Non-small cell lung cancer treatment; locally advanced (stage III) cancer" and "Patient information: Non-small cell lung cancer treatment; advanced unresectable, metastatic (stage IV), and recurrent cancer".)

Small cell lung cancer is discussed separately. (See "Patient information: Small cell lung cancer treatment".)

DEFINITION OF STAGE I AND II NON-SMALL CELL LUNG CANCER

Once non-small cell lung cancer is diagnosed, tests are performed to determine how far it has progressed or spread. This is referred to as "staging" the cancer. Cancer staging usually requires a combination of physical examination, x-ray studies, and sometimes an operation to evaluate the lymph nodes in the center of the chest (this area is called the mediastinum, and the lymph nodes contained within the mediastinum are called mediastinal lymph nodes) (figure 1).

Depending upon the findings, a specific tumor stage (I, II, III, or IV) is assigned, with stage I disease representing the earliest lung cancer, and stage IV, the most advanced (table 1) [1]. The stage is an important piece of information in patients with non-small cell lung cancer because it guides treatment options. The staging of lung cancer is described in detail elsewhere. (See "Patient information: Lung cancer risks, symptoms, and diagnosis".)

Patients with stage I or II non-small cell lung cancer are considered to have "local" or early stage lung cancer, and have a relatively low likelihood that the tumor has spread beyond one side of the chest.

Stage I — At this stage, tumor is present in the lungs but the cancer has not been found in the chest lymph nodes or in other locations outside of the chest. Stage I NSCLC is subdivided into stages IA and IB, usually based upon the size of the tumor or involvement of the pleura, which is lining along the outside of the lung (figure 2).

Stage IA — The tumor is 3 centimeters (cm) or less in size and has invaded nearby tissue minimally, if at all. The cancer has not spread to the lymph nodes or to any distant sites.

Stage IB — The tumor is more than 3 cm in size, has invaded the lining around the lung, or has caused a portion of the lung to collapse. The cancer has not spread to the lymph nodes or to any distant sites.

Stage II — At this stage, the cancer has either begun to involve the lymph nodes within the chest or has invaded chest structures and tissue more extensively. However, no spread can be found beyond the involved side of the chest, and the lung cancer is still considered to be local. Stage II is subdivided into stages IIA and IIB (figure 3).

Stage IIA — The tumor is 3 cm or smaller and has invaded nearby tissue minimally, if at all. One or more lymph nodes on the same side of the chest are involved, but there is no spread to distant sites.

Stage IIB — Stage IIB is assigned in two situations: when there is a tumor larger than 3 cm with some invasion of nearby tissue and involvement of one or more lymph nodes on the same side of the chest; or for cancers that have no lymph node involvement, but have either invaded chest structures outside the lung or are located within 2 cm of the carina (the point at which the trachea, or the tube that carries air to the lungs, splits to reach the right and left lungs.)

NON-SMALL CELL LUNG CANCER TREATMENT

Whenever possible, surgery is recommended for patients with stage I or II non-small cell lung cancer since surgery gives the highest chance for cure. Radiation therapy and chemotherapy may be recommended for people who are not good candidates for surgery due to severe lung disease or other underlying medical problems.

Surgery — Surgery to remove the cancer is the preferred treatment for stage I and stage II NSCLC. Options for surgery include the following:

• Lobectomy involves removal of one lobe of the lung. Lobes are a natural anatomic division of the lung.
• In some cases, pneumonectomy (removal of the entire affected lung) is necessary if lobectomy cannot completely remove the tumor. Pneumonectomy requires that the remaining lung be healthy and strong.
• A more limited surgical procedure, which removes less than a lobe of the lung, is possible for people who are unable to tolerate conventional lobectomy.

Radiation therapy — Radiation therapy involves the use of x-rays to destroy cancer cells. The x-rays are delivered from a machine that is outside of the patient. Treatments are brief and not painful. Small doses doses are given for a few seconds each day, five days per week, for several weeks.

The most common side effects of radiation therapy for lung cancer are difficulty swallowing due to inflammation of the esophagus, the tube between the mouth and stomach; this is called esophagitis. Pneumonitis, which is inflammation of the normal lung surrounding the tumor, can also occur. Both of these conditions are usually temporary and improve after treatment is completed.

Radiation alone may be used to treat patients with stage I or stage II non-small cell lung cancer who are unable to tolerate or who are not interested in surgery. Studies suggest that among patients with stage I or stage II lung cancer who receive radiation therapy alone, between 13 and 39 percent survive for five years or more [2].

Radiation therapy after surgery — Radiation therapy is sometimes recommended for people with stage II NSCLC who have been treated with surgery. When radiation is used in conjunction with another treatment, it is called "adjuvant" radiation therapy. Adjuvant RT decreases the chance that a tumor will return or recur following surgery. However, there is no evidence that radiation therapy improves survival [3].

Patients with stage I lung cancer do not appear to benefit from adjuvant RT.

Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy typically involves a combination of two or more drugs; these combinations are referred to as regimens. Most chemotherapy drugs are given IV. Chemotherapy is not usually taken daily, but periodically, in cycles. A cycle of chemotherapy refers to the time it takes to give the drugs and the time required for the body to recover.

Although patients with early stage lung cancer (stage I or II) do not have any evidence of distant spread when they are diagnosed, they are at risk to develop further cancer spread even after the cancer is surgically removed. In many people with early stage lung cancer, the cancer cells have spread through the body by the time the lung cancer is detected, even if distant spread cannot be found on x-rays. Thus, it is reasonable to use a body-wide treatment such as chemotherapy in an effort to eliminate these undetected cells.

Multiple large clinical trials have demonstrated a five-year survival benefit for people with stage II and IIIA non-small cell lung cancer who were treated with adjuvant cisplatin-based chemotherapy after surgery. For patients with stage IB disease, the data about the benefit of chemotherapy are conflicting. There is no evidence that chemotherapy has any benefits for people with stage IA disease.

Based upon these data, most physicians offer adjuvant cisplatin-based chemotherapy following surgical removal of stage II or IIIA non-small cell lung cancer. It may also be considered for selected patients with stage I NSCLC after surgery [4]. The chemotherapy is usually given into a vein for 3 to 4 cycles, lasting approximately 2 to 3 months in total.

Side effects — The most common side effects of cisplatin-based chemotherapy regimens include a lowered white blood cell count (which can increase the risk of infection), fever related to a low white blood cell count, nausea and vomiting, and constipation. These side effects are temporary and can be treated.

Adjuvant! online — A web-based assessment program (Adjuvant! Online, www.adjuvantonline.com) can help healthcare providers to estimate the relative risk of cancer recurrence and the potential benefits of chemotherapy. This estimate is based upon the patient's characteristics, features of the tumor, and proposed treatment. The program is not intended for patients to use on their own without the assistance of a healthcare provider.

PANCOAST TUMORS

The term Pancoast tumor (also called superior sulcus tumor) refers to a locally advanced non-small cell lung cancer that is located in the top part or apex of one of the lungs, in a region called the superior sulcus. These tumors can involve nerves in this region, causing a unique set of symptoms referred to as Pancoast's 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 there is a lack of sweating on the involved side (called Horner's syndrome). Cough and shortness of breath are less common in people with Pancoast's syndrome compared with lung cancers in other locations.

Superior sulcus tumors are staged in the same way as NSCLCs located elsewhere in the thorax. They usually fall into the category of stage IIB disease (T3,N0), but can also be more advanced (ie, stage IIIA [T3,N1-2], or IIIB [T4] disease, (table 1).

As a group, these tumors may have a better outcome as compared to non-small cell lung cancers in the center of the chest, particularly if there is no involvement of the lymph nodes in the mediastinum. In contrast to treatment of other patients with stage II NSCLC, treatment usually consists of a combination of chemotherapy and radiation followed by surgery, as long as there is no evidence of distant spread. Whenever possible, patients with superior sulcus tumors should be enrolled in prospective clinical trials so that the optimal therapy may be determined.

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. Ask for more information about clinical trials, or read about clinical trials at:

       www.cancer.gov/clinical_trials/learning/

       www.cancer.gov/clinical_trials/

       http://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Non-small cell lung cancer treatment; locally advanced (stage III) cancer
Patient information: Non-small cell lung cancer treatment; advanced unresectable, metastatic (stage IV), and recurrent cancer
Patient information: Small cell lung cancer treatment
Patient information: Lung cancer risks, symptoms, and diagnosis

Professional Level Information:
Adjuvant systemic therapy in resectable non-small cell lung cancer
Bronchioloalveolar carcinoma
Cigarette smoking and other risk factors for lung cancer
Diagnosis and staging of non-small cell lung cancer
Initial systemic chemotherapy for advanced non-small cell lung cancer
Investigational approaches for advanced non-small cell lung cancer
Management of malignant pleural effusions
Management of stage I and stage II non-small cell lung cancer
Management of stage III non-small cell lung cancer
Molecular markers in non-small cell lung cancer
Multiple primary lung cancers
Overview of the initial evaluation, treatment and prognosis of lung cancer
Pancoast's syndrome and superior (pulmonary) sulcus tumors
Pathology of lung malignancies
Role of imaging in the staging of non-small cell lung cancer
Sequential non-cross-resistant therapy for patients responding to initial treatment of advanced non-small cell lung cancer
Small molecule epidermal growth factor receptor inhibitors for advanced non-small cell lung cancer

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• The National Library of Medicine

      (www.nlm.nih.gov/medlineplus/lungcancer.html)

• National Cancer Institute

      (www.cancernet.nci.nih.gov/)

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• Global Resource for Advancing Cancer Education (GRACE)

      (www.cancerGRACE.org/lung)

• Lung Cancer Alliance

      (www.lungcanceralliance.org)

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