Friday, October 12, 2007

Treatment of early stage (stage I and II) non-small cell lung cancer

INTRODUCTION — Non-small cell lung cancer (NSCLC) accounts for between 75 and 85 percent of all lung cancers; the remaining 15 to 25 percent are small cell lung cancers. This distinction is important when considering treatment.

Once a NSCLC 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) (show figure 1).

Depending upon the findings of these procedures, a specific tumor stage (I, II, III, or IV) is assigned, with stage I disease representing the earliest cancer, and stage IV, the most advanced (show table 1) [1]. The stage is an important piece of information in patients with NSCLC because it determines treatment options. The staging of lung cancer is described in detail elsewhere. (See "Patient information: Diagnosis and staging of lung cancer").

The characteristics of early stage NSCLC (stage I and stage II disease), and the treatment options that are available for these patients will be reviewed here. The treatment of small cell lung cancer is discussed elsewhere. (See "Patient information: Treatment of small cell lung cancer").

DEFINITION OF STAGE I AND II DISEASE — Patients with stage I or II NSCLC are considered to have "local" disease, with a 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, mainly based upon the size of the tumor (show 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 surrounding tissue, 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 cancer is still considered a local disease. Stage II is subdivided into stages IIA and IIB (show 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.)

TREATMENT — Whenever possible, surgery should be considered for patients with stage I or II NSCLC since it is associated with the highest chance for cure. Radiation therapy and chemotherapy may be recommended in some patients.

An exception to these recommendations is with stage II NSCLC Pancoast tumors. These are located in the top part or apex of one of the lungs, in a region called the superior sulcus. They are unique in their presenting signs and symptoms and in the way they are treated. (See "Pancoast tumors" below).

Surgery — Surgery to remove the cancer is the preferred treatment for stage I and stage II NSCLC. Lobectomy (removal of one part (lobe) of the lung) through an open thoracotomy (large incision in the patient's chest) is the procedure of choice for patients with stages I and II NSCLC, and is preferred over pneumonectomy (removal of the entire affected lung) if the lesion can be completely removed. A pneumonectomy may be necessary if lobectomy cannot completely remove the tumor. Pneumonectomy requires that the remaining lung be healthy and strong enough to meet the patient's oxygen needs.

A more limited procedure is appropriate for those who are unable to tolerate conventional lobectomy. Limited resections are not recommended for tumors >3 cm in size whenever possible.

Outcomes — Outcomes of surgery vary according to the stage of the cancer, and to a lesser extent, the number of lung cancer surgeries performed in a patient's particular hospital. Patients who are treated in high volume centers tend to have slightly better outcomes compared to those undergoing treatment in low volume hospitals that see fewer patients with NSCLC. Stage I disease — Surgery alone is quite effective in treating stage I NSCLC. Studies have found that between 60 and 70 percent of patients with stage I NSCLC treated with surgery are still alive five years after the operation, and are presumably cured of their cancer. Stage II disease — Although surgery is less effective in treating patients with stage II NSCLC, it can cure many of these patients as well. Five year survival rates for patients with stage II NSCLC generally range between 30 and 40 percent.

Many patients with lung cancer have other lung conditions that increase their risk for complications following surgery. In particular, patients who are smokers may have chronic obstructive pulmonary disease (COPD, also called emphysema) that affects the lungs' ability to function. Breathing tests are usually performed before surgery to evaluate lung function and to predict how removal of a lung (or portion of a lung) will affect a patient's ability to breathe postoperatively. Occasionally, the tests may indicate that the risks of surgery are too great and that other forms of treatment must be used.

Radiation therapy — Radiation therapy involves the use of focused, high energy x-rays to destroy cancer cells. The x-rays are delivered from a machine (called a linear accelerator) that is outside of the patient. Treatments are brief and not painful. The damaging effect of radiation is cumulative, and a certain dose is required to stop the growth of cancer cells. In order to accomplish this, small radiation doses are administered daily, five days per week, for several weeks.

Radiation is administered to the areas of the body that are affected by the cancer. Thus, in contrast to chemotherapy, which is a systemic or body-wide treatment (see below), radiation is a local treatment, and side effects are generally limited to the area undergoing radiation. These side effects occur because some normal tissues next to the tumor inevitably are exposed to some of the radiation. The most common side effects are difficulty swallowing due to inflammation of the gastrointestinal tract (termed esophagitis) and inflammation of the normal lung surrounding the tumor (termed pneumonitis). Both of these conditions are usually self-limited and improve after treatment is completed.

Radiation alone may be used to treat patients with stage I or stage II NSCLC who are unable to tolerate or who are not interested in surgery. Although not as effective as surgery, it is more effective than no treatment at all. Studies suggest that among patients with stage I or stage II disease who receive radiation therapy alone, between 13 and 39 percent survive for five years or more [2].

Postoperative radiation therapy — Radiation therapy is sometimes recommended in patients with stage II NSCLC who have been treated with surgery. When 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, it does not appear to prolong survival [3]. Radiation is more likely to be recommended if small amounts of tumor are thought to remain after surgery, and for those who have substantial involvement of the lymph nodes.

Patients with stage I disease do not appear to benefit from adjuvant RT. In fact, some studies suggest that such treatment actually decreases the chances of survival.

Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult's normal cells are not actively growing, they are not affected by chemotherapy. However, the bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract are actively growing, and the effects of chemotherapy on these and other normal tissues cause side effects commonly seen during treatment. Most chemotherapy drugs are administered into a vein, although some agents can be given by mouth.

Chemotherapy is most often used for patients with advanced NSCLC (stage IV), although it may be considered for those with earlier stage disease.

Adjuvant (postoperative) chemotherapy — Although patients with early stage NSCLC (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. It is believed that, in many patients with early stage NSCLC, 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, using a body-wide treatment such as chemotherapy in an effort to eliminate these undetected cells is reasonable.

Multiple large clinical trials have demonstrated that adjuvant chemotherapy with a cisplatin-based regimen improved five-year survival following resection of NSCLC in patients with stage II, III, and possibly IB disease. There is no evidence to support a benefit in patients with stage IA disease [4].

Based upon these data most physicians recommend that adjuvant cisplatin-based chemotherapy be offered to all patients following surgical removal of stage II or IIIA NSCLC. For patients with stage IB disease the data are conflicting, although studies suggests a small survival advantage for adjuvant chemotherapy.

PANCOAST TUMORS — The term Pancoast tumor (also called superior sulcus tumor) refers to a locally advanced NSCLC that is located in the top part or apex of one of the lungs, in a region called the superior sulcus. Because of their location, these tumors cause a unique set of symptoms including shoulder and arm pain, weakness of the muscles of the hand, and a droopy eyelid associated with flushing or excessive sweating on one side of the face (called Horner's syndrome); this constellation of symptoms is referred to as Pancoast's syndrome. Cough and shortness of breath are less common in Pancoast's sydrome than 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, show table 1).

As a group, these tumors may have a better outcome as compared to NSCLCs 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:

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 patients 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 ( Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

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. National Cancer Institute

People Living With Cancer: The official patient information

website of the American Society of Clinical Oncology
The American Cancer Society

Lung Cancer Alliance


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Mountain, CF. Revisions in the international system for staging lung cancer. Chest 1997; 111:1710.
2. Rowell, NP, Williams, CJ. Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (Medically inoperable) (Cochrane Review). Cochrane Database Syst Rev 2001; 2:CD002935.
3. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Available at (Accessed 3/7/05).
4. Pignon, JP, Tribodet, H, Scagliotti, GV, et al. Lung Adjuvant Cisplatin Evaluation (LACE): A pooled analysis of five randomized clinical trials including 4,584 patients. J Clin Oncol 2006; 24:366s. (Abstract 7008). Abstract available on line (, accessed on June 7, 2006).

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