Patient information: Lung cancer risks, symptoms, and diagnosis

INTRODUCTION

Lung cancer is a serious health problem that affects many patients and their families. Lung cancer is the leading cause of cancer death in the United States and throughout the world. It is usually caused by cigarette smoke but there are other important risks in the home and in the work-place.

When a person develops lung cancer, tests are done to determine the type of lung cancer and the stage of the disease. This topic will review the risks for developing lung cancer, the different types of lung cancer, signs and symptoms of lung cancer, and the medical testing required to confirm the diagnosis and determine the cancer's size and location.

RISKS FOR LUNG CANCER

Cigarette smoking is the biggest risk factor for lung cancer; it causes 90 percent of all lung cancers in the United States. A smoker's risk of developing lung cancer is 10 to 30 times greater than that of a non-smoker. All forms of tobacco and smoking, including pipes, cigars, and chewing tobacco are major risk factors for cancers of the mouth, throat, and lungs.

The risk of lung cancer increases with the number of cigarettes smoked and the number of years of smoking. One way to estimate the risk of developing lung cancer is to multiply the number of packs (20 cigarettes per pack) smoked per day by the number of years smoked. For example, a person who smoked one pack per day for 20 years would have a 20-pack-year exposure. The risk of developing lung cancer increases quickly after 20 pack-years.

Smokers who have quit — The risk of cancer remains high for several years after a person stops smoking, but generally decreases to lower levels within five to 10 years after quitting (table 1). Unfortunately, a former smoker's risk of developing lung cancer is never as low as a non-smoker's.

Lung cancer in non-smokers — Exposure to substances at work or in the environment can increase a person's risk of developing lung cancer. Substances that increase the risk of cancer include second-hand tobacco smoke, asbestos, arsenic, radiation, and some chemicals, such as polycyclic hydrocarbons. Dust and fumes from nickel, chromium, and other metals that can be inhaled or ingested may also increase the risk of lung cancer.

An important risk factor for lung cancer in the home is radon. Radon is a radioactive gas that occurs naturally in the ground. Radon can leak out of the ground and then become trapped in houses or buildings, where it is then inhaled.

Many non-smokers who develop lung cancer have no known risk factors. In these cases, it is not usually possible to determine why the person developed lung cancer.

Age and genetic risk factors — The risk of developing lung cancer increases with age. Lung cancer can occur in young people, although it is unusual in people less than 40 years old. After age 40, the risk for developing lung cancer slowly increases every year.

Some people have a genetic risk or predisposition for lung cancer. Anyone with a first degree relative (parent, brother, sister) with lung cancer has a higher risk of developing lung cancer themselves.

TYPES OF LUNG CANCER

There are many different kinds of lung cancer. These types can be differentiated only by examining a piece of the cancer with a microscope. Lung cancers are classified into two main categories:

• Small cell lung cancer, also known as "oat cell cancer" is found in about 10 to 15 percent of patients.
• Non-small cell lung cancer (abbreviated NSCLC) includes other types of lung cancer, and is found in the remaining 85 to 90 percent of patients. There are sub-categories of NSCLC, the most common of which are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

The reason that small cell cancer is separated from the other non-small cell cancers is that small cell cancers behave differently and are treated differently. Small cell cancer tends to be more aggressive, can spread quickly, and may be treated with chemotherapy or a combination of chemotherapy and radiation.

Non-small cell cancer has a wide range of growth patterns and may be treated with surgery, chemotherapy, or radiation. For both types of lung cancer, the stage of the disease determines what treatments are most likely to be effective.

SYMPTOMS

Most patients develop symptoms as a result of their lung cancer. It is less common for a person to have no symptoms at all. Occassionally, a tumor may be found because a chest x-ray or CT scan was done for a reason not related to lung cancer symptoms.

It is important to remember that the symptoms of lung cancer are also symptoms of many other lung problems, such as pneumonia, bronchitis or emphysema. Thus, having one or more of these symptoms does not always mean that cancer is present. (See "Patient information: Pneumonia in adults" and "Patient information: Chronic obstructive pulmonary disease (COPD)".)

The symptoms of lung cancer can be divided into groups based on the part of the body affected by the tumor. Symptoms of lung cancer can be caused by one or more of the following:

• Tumor in the lungs or chest
• Tumor that has spread or metastasized to other parts of the body
• Indirect tumor effects such as weight loss and fatigue

Lung and chest symptoms — Lung or chest symptoms are caused by the tumor pressing on structures of the chest or invading the organs in the chest. Cough is the most common symptom. Other chest symptoms can include shortness of breath, chest pain, and wheezing. Less common symptoms include voice changes, swelling, arm pain, and shoulder pain.

• Cough — Lung cancer can cause a new cough. It may also cause the cough to change in a person who has had a longstanding (chronic) cough. The cough can be a dry cough or may produce sputum (phlegm). Worrisome features of a chronic cough include a more frequent or severe cough. Cancer may cause more sputum or may cause the sputum to be bloody. Anyone who coughs up bright red or clotted blood needs immediate medical attention. (See "Patient information: Chronic cough in adults".)

• Shortness of breath may develop if the cancer blocks or narrows one of the breathing tubes or wind-pipe (called a bronchus or the trachea). Shortness of breath can also develop if the tumor causes the lung, the chest cavity or the area around the heart to fill with fluid.
• Wheezing is a whistling sound that can develop if the tumor blocks or narrows the airways.
• Chest pain can occur if the tumor invades the ribs, walls of the chest, or the lining around the lung. Chest pain can also occur if there is compression of the structures in the center of the chest or enlargement of lymph nodes in the chest. The pain may be described in different ways, including dull, sharp, stabbing, vague, and sometimes just in a single spot.
• Voice hoarseness may develop if the tumor presses on the nerves around the trachea, which control the voice box.
• Headache and swelling of the face, arms, or neck can occur if the tumor presses on the large blood vessels as they pass back into the chest.
• Arm, shoulder and neck pain, as well as face changes, can be caused by a tumor in the top of the lungs. The Pancoast syndrome happens when a tumor grows through the very top part of the lung and presses on the nerves that control the arms and face. Symptoms can include shoulder or arm pain, weakening of the hand muscles (due to pressure on the nerve that stimulates the arm), a droopy eyelid, and blurred vision.

Symptoms of cancer spread (metastasis) — Lung cancer can spread or metastasize to other parts of the body. The most common places for metastases are the bones, liver, brain, and adrenal glands.

Bone metastases can cause localized pain in the bone or may cause the bone to break, often without any trauma. Bones that are commonly affected by metastasis include the spine, ribs and pelvis, although any bone may be affected.

Metastasis to the liver may cause weakness, jaundice (yellowing of the skin) and weight loss. Brain metastases can cause a range of symptoms, including headache, nausea and vomiting, seizures, confusion, and personality changes.

Indirect tumor symptoms — Lung cancer may produce substances that travel in the blood and have effects throughout the body. These substances can cause symptoms that are not directly connected to the lungs and often difficult to describe. These symptoms are referred to as "paraneoplastic syndromes".

Only 10 to 20 percent of patients with lung cancer will experience symptoms due to a paraneoplastic syndrome. These symptoms do not necessarily mean that the tumor has spread or is untreatable.

Common paraneoplastic symptoms include the following:

• Weight loss
• Low appetite or a sensation of a full stomach after eating small amounts of food
• Broadening and thickening of the fingernails (called digital clubbing)
• Painful or swollen joints
• Muscle symptoms such as muscle weakness, pain or stiffness
• Breast enlargement or discharge of a milky substance from the nipples
• Fever
• Blood changes such as anemia, blood clots or other changes in the blood cell numbers
• Blood pressure changes, either too high or too low
• An increase in the calcium level (called hypercalcemia)
• A decrease in the concentration of sodium in the blood (called hyponatremia)

INITIAL TESTING AND DIAGNOSIS

If a person has symptoms that suggest lung cancer, a healthcare provider will perform a complete medical history and physical examination. This should include a thorough review of medical problems, a discussion of risk factors for lung cancer, and a physical examination. After the examination, a chest X-ray is performed. An imaging test called a CT scan is usually done at this time as well.

If the chest x-ray or CT scan shows a mass that could be a tumor, additional testing is performed. This may include blood work and, if not already done, a CT scan of the lower neck, entire chest, and upper part of the abdomen. The CT scan is useful because it shows the entire inside of the chest, which helps the physician determine if the lung cancer has spread outside the lung (figure 1). Other imaging tests that may be used include PET scanning, bone scanning, and brain scanning.

However, lung cancer cannot be diagnosed with an x-ray or imaging test alone. The diagnosis is confirmed only after a small piece of the tumor is examined with a microscope. This means that a procedure is needed to remove a piece of tumor from the lung or another place that the tumor has spread. This procedure is called a biopsy. There are several ways that this biopsy can be done:

• Bronchoscopy is a procedure where a flexible tube is inserted through the mouth into the windpipe (called the trachea). A camera and light at the tip of the instrument allow the physician to see in the large air tubes of the lung. Using small instruments, the doctor can biopsy the tumor or lymph nodes. Most patients require intravenous (IV) medications similar to morphine or valium and do not require general anesthesia. (See "Patient information: Fiberoptic bronchoscopy".)
• CT-guided fine needle aspirate biopsy is a biopsy that is performed by a radiologist (a physician who specializes in imaging studies like CT scan). The physician numbs the skin and then inserts a thin needle through the skin of the chest into the lung. The needle's location is guided by CT scan.
• Needle aspiration is a procedure that is done if there are lumps that can be felt under the skin or if there are fluid collections in the chest. During this procedure, the skin over the area is cleaned and numbed. A needle is then placed through the skin into the lump or pocket of fluid in the chest. The needle will fill with tissue or fluid, which is then removed and examined under a microscope to determine if cancer cells are present.
• Surgery may be needed if the tumor is small and a biopsy sample cannot be obtained any other way. Lung and chest surgery requires many pre-operative tests and preparation. Part of the preparation for a surgery is a discussion of the importance of stopping smoking before the surgery. (See "Patient information: Smoking cessation".)

There are several surgical methods; the optimal procedure depends upon the size of the tumor and its location. Surgery can be done to remove large potions of lung or small pieces of lung, called a "wedge".

Sometimes, the surgery performed to obtain a biopsy sample is intended to cure the cancer. Alternatively, surgery called mediastinoscopy may be done to biopsy lymph nodes in the center of the chest to establish the diagnosis and determine whether the cancer has spread.

STAGING OF NON-SMALL CELL LUNG CANCER

Staging is a way for physicians to indicate how much tumor is present and where the tumor is located. The stage of an lung cancer is defined by a Roman numeral designation between I and IV, and subdivided by the letters A, B, and C (table 2). The stage is assigned based upon the result of the diagnostic testing, and is important in determining the most appropriate treatment.

In addition, staging provides important information about prognosis. In general, chances of survival and cure are best with stage I disease and worsen as the stage increases.

This topic review uses the current (sixth) version of the TNM staging system. A seventh version has been proposed, and is likely to be adopted. Differences between the sixth and seventh versions of the staging system are described in table 3 (table 3).

The goal of the staging work-up is to determine three features:

  1) The size and extent of the initial tumor

  2) If tissues in the chest have been invaded by the tumor

  3) If the tumor has spread to other places outside the chest

These three features are examined carefully to determine characteristics of the tumor, known as T, N and M (table 2).

• The characteristics of the tumor (T category)
• The presence or absence of spread to lymph nodes (N category)
• Spread (metastasis) to distant locations in the body (the M category)

Combinations of T, N, and M are grouped together in the final stage group. Staging involves closely examining several critical areas of the chest (figure 1). These critical areas include:

• Pleura — The thin membrane surrounding the lung
• Trachea — The main airway that brings air from the mouth to the chest
• Bronchus — The right and left airways that are the first branches of the trachea
• Carina — The dividing point between the right and left main bronchi
• Mediastinum — The space between the lungs in the middle of the chest. The mediastinum contains the heart, great blood vessels, and esophagus.
• Lymph nodes — Small clumps of tissue that are found along the large airways and in the mediastinum. Ipsilateral lymph nodes refer to lymph nodes in the lung on the same side as the original tumor. Contralateral lymph nodes are on the opposite side of where the tumor first developed. Mediastinal lymph nodes are in the space between the lungs.

Stage I — Stage I NSCLC is the earliest stage cancer. It occurs when there has been no visible spread of the tumor to lymph nodes or outside the chest. Stage I lung cancer is considered "local" or "localized" disease because the tumor has not grown beyond the initial location where it started.

Stage I disease is subdivided into stages IA and IB, based upon the size of the tumor.

• Stage IA is a tumor that is less than 3 centimeters (about 1.2 inches) in diameter (figure 2).
• Stage IB is a tumor that is larger, has extended up to the pleura surrounding the lung, or has caused a portion of the lung to collapse. Stage IB is also present if the tumor is in one of the main bronchi but is more than 2 cm away from the carina (figure 2). (See "Patient information: Non-small cell lung cancer treatment; early stage (stage I and II) cancer".)

Stage II — Stage II cancers have either metastasized to lymph nodes, have invaded the tissues surrounding the lung, or have started to invade the central structures of the lung. In stage II lung cancer, there are no metastases outside the chest and the cancer is still considered a local disease. The affected lymph nodes are only within the lung where the tumor is located. (See "Patient information: Non-small cell lung cancer treatment; early stage (stage I and II) cancer".)

Stage II NSCLC is subdivided into stages IIA and IIB.

• Stage IIA is present if the tumor is smaller than 3 cm, although there is metastasis to lymph nodes on the side of the chest where the tumor is located (figure 3).
• Stage IIB is present if the tumor is bigger than 3 centimeters in diameter and has spread to the lymph nodes within the lung on the same side of the chest. Stage IIB is also present if the tumor has started to invade the main bronchi in the center of the chest (within 2 cm of the carina), or has spread through the pleura. Stage IIB tumors do not include tumors that have metastasized to the lymph nodes in the middle of the chest (mediastinum) (figure 3).

Stage III — Stage III tumors are more advanced than stages I and II, but have not yet spread outside of the chest. Stage III disease is present if there has been spread to the lymph nodes in the center of the chest or if the tumor extensively involves the structures connected to the lungs. (See "Patient information: Non-small cell lung cancer treatment; locally advanced (stage III) cancer".)

Stage III NSCLC is subdivided into stages IIIA and IIIB.

• Stage IIIA is present if the tumor has invaded through the membrane surrounding the lung and into adjacent structures, such as the chest wall or diaphragm, or into lymph nodes in the middle of the chest (mediastinum) (figure 4).
• Stage IIIB tumors have extensive invasion into the mediastinum, (trachea, blood vessels, heart, esophagus), or may have spread to lymph nodes on the opposite side of the mediastinum. Patients with fluid collections in the chest caused by cancer (called pleural effusions) also are classified as having stage IIIB disease (figure 4).

Stage IV — In stage IV disease, the cancer has metastasized to the opposite lung or to distant locations outside the chest (eg, the brain or bones). The original tumor may be any size or have any degree of lymph node metastasis (figure 5). (See "Patient information: Non-small cell lung cancer treatment; advanced unresectable, metastatic (stage IV), and recurrent cancer".)

STAGING SMALL CELL LUNG CANCER

The T, N and M system used to stage NSCLC is not commonly used in staging small cell lung cancer (SCLC). This is because SCLC tends to have different growth patterns and a different prognosis. SCLC is categorized more simply as either "limited" or "extensive" disease. This classification is useful in determining the best approach to treatment.

Limited disease — This refers to small cell lung cancers that are confined to one side of the chest.

Extensive disease — This refers to small cell lung cancers that have spread to both sides of the chest or have metastasized to distant locations outside the chest.

The treatment and prognosis of SCLC depends upon the classification. This is discussed in detail in a separate topic review. (See "Patient information: Small cell lung cancer treatment".)

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: Pneumonia in adults
Patient information: Chronic obstructive pulmonary disease (COPD)
Patient information: Chronic cough in adults
Patient information: Fiberoptic bronchoscopy
Patient information: Smoking cessation
Patient information: Non-small cell lung cancer treatment; early stage (stage I and II) cancer
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

Professional Level Information:
Adjuvant systemic therapy in resectable non-small cell lung cancer
Cigarette smoking and other risk factors for lung cancer
First-line chemotherapy for 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 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
Overview of the risk factors, pathology, and clinical manifestations of lung cancer
Pathobiology and staging of small cell carcinoma of the lung
Pathology of lung malignancies
Preoperative evaluation for lung resection
Role of imaging in the staging of non-small cell lung cancer
Screening for lung cancer
Small molecule epidermal growth factor receptor inhibitors for advanced non-small cell lung cancer
Treatment of refractory and relapsed small cell lung cancer
Women and 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)

[1-6]