Tumor biomarkers for diagnosis, prognosis and targeted therapy | Signal Transduction and Targeted Therapy

Stages Of Non-Small Cell Lung Cancer

Doctors stage non-small cell lung cancer (NSCLC) according to how far it has progressed. Stages range from occult (or hidden) cancer to stage 4 cancer, in which multiple organs may be affected.

Several different staging systems for non-small cell lung cancer (NSCLC) are used worldwide, but the most widely used approach is the TNM system.

A staging system helps doctors determine the best treatment plan and helps individuals with cancer and their families understand the severity of the disease and the outlook.

This article will examine the TNM stages of NSCLC and the cancer traits and grouping for each stage.

The TNM system for NSCLC staging considers the size and location of the tumor, as well as what other parts of the body are involved:

T refers to the primary tumor, focusing on its size (usually in centimeters) and whether it is isolated or has penetrated nearby tissue.

N is used to describe the number of nearby lymph nodes that also contain cancer cells.

M refers to whether the cancer has metastasized, meaning it has traveled from the primary tumor to other body organs and tissue.

In addition to the TNM classifications, doctors use six stages to further describe the cancer. Stages 1 through 4 are divided into substages, as shown in this table:

At the occult stage, the main cancerous tumor can't be found (TX). Cancer cells might be found in phlegm or other lung fluid but not in other tests. The cancer isn't thought to have traveled to the lymph nodes (NO) or other parts of the body (MO).

In stage 0, the tumor is contained to the top layer of the airways and not deep into other lung tissue (Tis). The cancer also hasn't spread to the lymph nodes (NO) or other parts of the body (MO).

Doctors divide stage 1 NSCLC into four further classifications:

stage 1A1

stage 1A2

stage 1A3

stage 1B

Stage 1A1

The characteristics of stage 1A1 are as follows:

The adenocarcinoma is minimally invasive and no bigger than 3 centimeters (cm) across.

The portion that has spread into the lung tissue is no more than 0.5 cm across (T1mi).

The tumor is no more than 1 cm across and has not penetrated the lungs' main air passages (bronchi) or the membranes around the lungs (T1a).

The cancer hasn't reached the lymph nodes (NO) or elsewhere in the body (MO).

Stage 1A2

In stage 1A2, the tumor is between 1 cm and 2 cm across and hasn't affected the bronchi or penetrated the visceral pleura (T1b), which covers the surface of each lung. It also hasn't reached the lymph nodes (NO) or distant body parts (MO).

Stage 1A3

In stage 1A3, the tumor is between 2 cm and 3 cm across and hasn't migrated to the visceral pleura or the main branches of the bronchi (T1c). The cancer still hasn't reached the lymph nodes (NO) or other parts of the body (MO).

Stage 1B

In stage 1B, the tumor hasn't reached the lymph nodes (NO) or other body parts (MO) but has at least one of the following traits (T2a):

It's between 3 cm and 4 cm across.

It's no more than 4 cm across and has penetrated a main bronchus, but isn't within 2 cm of where the windpipe forks into the left and right bronchi.

It has migrated into the visceral pleura and is no more than 4 cm across.

It's no more than 4 cm across but is partially blocking the airways.

Stage 2 is broken down into two classifications:

Stage 2A

At this stage, the cancer is still contained in the lungs and hasn't spread to nearby lymph nodes (NO) or distant body parts (MO). However, the tumor has at least one of the following characteristics (T2b):

It's between 4 cm and 5 cm across.

It's between 4 cm and 5 cm and has reached a main bronchus but is still at least 2 cm away from the carina. The carina is a ridge of cartilage at the base of the windpipe that separates the openings for the main bronchi.

It has entered the visceral pleura but is still between 4 cm and 5 cm across.

It's between 4 cm and 5 cm and is partially blocking the airways.

Stage 2B

In this stage, the tumor is no bigger than 3 cm across but hasn't migrated to the visceral pleura or the branches of the bronchi (T1). It has, however, spread to the lymph nodes in or around the lungs on the same side as the tumor (N1) but not distant parts of the body (MO).

Or, the tumor has at least one of the following traits (T2):

It's between 3 cm and 5 cm across.

It's no more than 5 cm across and growing into a main bronchus, but is still at least 2 cm away from the carina.

It's no more than 5 cm across and has grown into the visceral pleura.

It's no bigger than 5 cm across and is partially blocking the airways.

In stage 2B, the cancer may also have reached the lymph nodes in or near the lungs on the same side as the tumor (N1) but hasn't spread to distant body parts (MO).

Or, the tumor hasn't reached the nearby lymph nodes (NO) or the distant body parts (MO) but has at least one of these following characteristics (T3):

It's between 5 cm and 7 cm across.

It's grown into the chest wall, the chest wall's inner lining (parietal pleura), the phrenic nerve (which controls the diaphragm), or the thin sac that surrounds the heart (parietal pericardium).

There are at least two separate nodules in the same lobe of a lung.

Stage 2B grouping

T1a/T1b/T1c

N1

MO

T2a/T2b

Stage three has three classifications:

stage 3A

stage 3B

stage 3C

Stage 3A

Stage 3 NSCLC is considered an advanced stage of the disease. However, it's treatable in many cases, with positive outcomes still possible. This stage covers a wide range of paths the cancer may be taking.

Path 1

In this case, the tumor is no more than 3 cm across, doesn't touch the main branches of the bronchi (T1), and hasn't reached the visceral pleura. It has spread to the lymph nodes on the same side as a main tumor (N2) but hasn't extended to distant body parts (MO).

Or, the tumor has at least one of the following traits (T2):

It's between 3 cm and 5 cm across.

It has reached a main bronchus but is still at least 2 cm away from the carina and is no more than 5 cm across.

It has entered the visceral pleura but is no more than 5 cm across.

It's no bigger than 5 cm across but is partially clogging the airways.

Path 2

In this case, the cancer has reached the lymph nodes near the main tumor (N2) but hasn't spread to distant body parts (MO).

Or, the tumor has at least one of the following features (T3):

It's between 5 cm and 7 cm across.

It has migrated into the chest wall, parietal pleura, phrenic nerve, or parietal pericardium.

There are at least two separate nodules in the same lobe of a lung.

Path 3

In this path of NSCLC, the cancer has spread to the nearby lymph nodes on the same side as the main tumor (N1) but hasn't reached other body parts (MO).

Or, the tumor has at least one of the following traits (T4):

It's at least 7 cm across.

It's grown into the tissue between the lungs (mediastinum), heart, large blood vessels in or near the heart, trachea, esophagus, diaphragm, spine, or carina.

There are at least two nodules in different lobes of the same lung.

The cancer may have spread to the lymph nodes in or near the lungs. If that has occurred, the lymph nodes are on the same side as the main tumor (NO or N1). The cancer hasn't spread to distant body parts (MO).

Stage 3A grouping

T1a/T1b/T1c

T2a/T2b

T3

T4

NO

N1

N2

MO

Stage 3B

This stage can also mean many different paths for the NSCLC.

Path 1

One possibility is that the cancer is no more than 3 cm across, hasn't entered the visceral pleura, and doesn't affect the main branches of the bronchi (T1).

However, the cancer has reached the lymph nodes close to the collarbone on either side of the body and may have also spread to the lymph nodes near the lungs on the side opposite the main tumor (N3). The cancer hasn't spread to distant parts of the body (MO).

Or, the tumor has at least one of the following traits (T2):

It's between 3 cm and 5 cm across.

It's no more than 5 cm across and has grown into the main bronchus, but is still at least 2 cm from the carina.

It has penetrated the visceral pleura and is no more than 5 cm across.

It's no more than 5 cm across but is partially blocking the airways.

Path 2

In this scenario, the cancer has reached the lymph nodes close to the collarbone on either side of the body or has spread to the lymph nodes in or near the lungs on the opposite side from the main tumor (N3). This cancer hasn't reached distant parts of the body (MO).

Or, the tumor has at least one of the following traits (T3):

It's between 5 cm and 7 cm across.

It has grown into the chest wall, parietal pleura, phrenic nerve, or parietal pericardium.

There are at least two separate nodules in the same lobe of a lung.

Path 3

In this case, the cancer has reached the lymph nodes near the carina or in the mediastinum on the side of the main tumor (N2) but hasn't traveled to distant parts of the body (MO).

Or, the tumor has at least one of the following characteristics (T4):

It's at least 7 cm across.

It's grown into the mediastinum, heart, large blood vessels in or near the heart, trachea, esophagus, diaphragm, spine, or carina.

There are at least two separate tumor nodules in different lobes of the same lung.

Path 4

In the path 4 scenario, the cancer has made its way to the lymph nodes surrounding the carina or in the mediastinum on the same side as the main tumor (N2). However, the cancer has not spread to distant body parts (MO).

Stage 3B grouping

T1a/T1b/T1c

T2a/T2b

T3

T4

N2

N3

MO

Stage 3C

At this stage, the tumor has at least one of the following features:

It's between 5 cm and 7 cm across.

It's migrated into the chest wall, parietal pleura, phrenic nerve, or parietal pericardium.

There are at least two separate nodules in the same lobe of a lung.

The cancer has also spread to the lymph nodes close to the collarbone on either side of the body and may have reached lymph nodes on either side of the body from the main tumor (N3). The cancer hasn't reached distant body parts (MO).

Other characteristics of this stage

In this stage, the tumor may also have at least one of the following characteristics (T4):

It's at least 7 cm across.

It has grown into the mediastinum, heart, large blood vessels in or near the heart, trachea, esophagus, diaphragm, spine, or carina.

There are at least two separate tumor nodules in different lobes of the same lung.

The cancer may also have spread to the lymph nodes close to the collarbone on either side of the body and may have reached lymph nodes on either side of the body from the main tumor (N3). The cancer hasn't reached distant body parts (MO).

Stage 4A

At stage 4, the tumor may be any size, and the cancer may have extended into nearby tissue (any T). Likewise, it may not have reached nearby lymph nodes (any N).

For M1a grouping, at least one of the following traits must be present:

The cancer is now in both lungs.

Cancer cells are present in the fluid surrounding the lung, known as a malignant pleural effusion.

Cancer cells are discovered in the fluid-filled pericardium around the heart. This is known as a malignant pericardial effusion.

Or, the tumor may be any size, and the cancer may have extended into nearby tissue (any T). It may also involve any of the nearby lymph nodes (any N).

In addition, it has spread as one tumor outside of the chest cavity to a distant lymph node or an organ, such as the brain or liver (M1b).

Stage 4B

At stage 4, the tumor may be any size, and the cancer may have extended into nearby tissue (any T). Likewise, it may have reached nearby lymph nodes (any N).

The cancer has also spread as at least two tumors outside the chest cavity to distant lymph nodes and other organs (M1c).

As precise as these stages and groupings may seem, health experts acknowledge that classifying the state of a particular NSCLC is imperfect.

One 2017 study found that, as NSCLC progresses, staging accuracy declines. The authors recommend that an individual's healthcare team reassess the status of the cancer after every surgery or test to build a consensus about the next phase of treatment.

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