Metastasis

Metastasis is when cancer spreads from where it started to other parts of the body. While most cancer-related deaths happen because of metastasis, new treatments are helping some people live longer with this advanced form of the disease.

Table of contents

• What is metastasis?
• How cancer spreads
• Where cancer commonly spreads
• Signs and symptoms
• What causes metastasis
• Diagnosis
• Treatment
• Outlook and prognosis
• Living with metastatic cancer

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What is metastasis?

Metastasis is the spread of cancer from the place in the body where it first started to a different area^[1]. When cancer spreads to another part of the body, it is called metastatic cancer or stage 4 cancer^[2]. The process by which cancer cells spread to other parts of the body is called metastasis^[5].

The newly formed tumors in distant parts of the body are called metastases (or “mets” for short)^[3]. Metastasis is generally different from cancer invasion, which is when cancer cells directly extend into neighboring tissues without traveling through the blood or lymphatic system^[3].

When cancer spreads to another part of the body, it keeps the same name as the original cancer. For example, if breast cancer spreads to the lungs, it is still called metastatic breast cancer, not lung cancer^[5]. The cancer cells in the new location are similar to those in the original tumor^[2].

Metastasis is one of the key features that distinguishes cancer from benign tumors^[3]. Nearly all cancers have the potential to metastasize, although they do so at varying rates^[2]. Some cancers, like basal cell carcinoma, rarely spread to other parts of the body^[3].

Most cancer-associated deaths occur due to metastasis, not the primary tumor itself^[4]. More than 90% of patients with cancer die as a consequence of their metastatic disease^[4]. Unlike primary tumors, which often can be cured with local therapies such as surgery and radiation, metastatic cancer is a systemic disease that affects multiple organs^[4].

How cancer spreads

Cancer cells spread through the body in a series of steps^[5]. First, they grow into or invade nearby normal tissue. Then they move through the walls of nearby lymph nodes or blood vessels and travel through the lymphatic system (a group of tissues and organs that make and store cells that fight infection) or bloodstream to other parts of the body^[5].

There are three main ways metastases can occur^[2]:

• Cancer cells can grow directly into the tissue surrounding the primary tumor
• They can travel through the bloodstream to distant locations like other organs or bones
• They can move through the lymphatic system to nearby or distant lymph nodes

Some cancer cells, known as circulating tumor cells, are able to penetrate the walls of lymphatic or blood vessels and circulate through the bloodstream to other sites and tissues in the body^[3]. These cells can travel not only as single cells but also as groups of cells, called circulating tumor cell clusters^[3].

Once these traveling cells stop in small blood vessels at a distant location, they invade the blood vessel walls and move into the surrounding tissue. There they grow until a tiny tumor forms. They then cause new blood vessels to grow, creating a blood supply that allows the metastatic tumor to continue growing^[5].

Most of the time, spreading cancer cells die at some point in this process. But as long as conditions are favorable for the cancer cells at every step, some of them are able to form new tumors in other parts of the body^[5]. The immune system usually attacks and destroys cancer cells that travel through the lymphatic system or blood, but sometimes cancer cells survive and settle in another area of the body^[6].

Metastatic cancer cells can also remain inactive at a distant site for many years before they begin to grow again, if at all^[5].

Where cancer commonly spreads

Cancer can spread to almost any part of the body, although different types of cancer are more likely to spread to certain areas than others^[5]. The most common sites where cancer spreads are bone, liver, and lung^[5]. Other common sites include the adrenal glands, brain, lymph nodes, and peritoneum (the membrane that lines the abdomen)^[2].

Where cancer spreads during metastasis depends on the location of the primary tumor^[2]. For example:

• Breast cancer often spreads to bone, brain, liver, and lung^[5]
• Colorectal cancer tends to spread to the liver, lung, and peritoneum^[5]
• Lung cancer commonly spreads to the adrenal gland, bone, brain, liver, and other lung^[5]
• Prostate cancer typically spreads to the adrenal gland, bone, and liver^[5]
• Ovarian cancer usually spreads to the liver, lung, and peritoneum^[5]

Signs and symptoms

Metastatic cancer does not always cause symptoms^[5]. Cancer cells can grow and spread gradually over many months or years. In some instances, it is possible to have stage 4 cancer and not know it^[2].

When symptoms do occur, what they are like and how often they happen depends on the size and location of the metastatic tumors^[5]. General symptoms of metastasis may include^[2]:

• Extreme fatigue
• Night sweats
• Unexplained weight loss

Some signs of metastatic cancer depend on the location of the primary tumor and where the cancer cells spread. Depending on the type of metastasis, symptoms might include^[2]:

• Bloating, swollen belly, decreased appetite, getting full quickly, or jaundice (yellowing of the skin and eyes), which are common in liver metastases
• Bone pain or fractures, common in bone metastases^[5]
• Dizziness, headaches, or seizures, common in brain metastases^[5]
• Shortness of breath, common in lung metastases^[5]

What causes metastasis

Metastasis happens when cancer cells break off from the original tumor and spread to other parts of the body^[2]. Whether or not a cancer spreads depends on many things, including the type of cancer, how fast the primary cancer is growing and how likely it is to spread, the size and location of the primary cancer, how long the primary cancer has been in the body, and whether cancer treatments were used and how well they worked^[6].

Many factors can trigger metastasis^[2]:

• A weakened immune system
• Hypoxia (a lack of oxygen in tissues)
• Lactic acidosis (a buildup of lactic acid in the blood)
• Autophagy (a type of cell death)

At the cellular level, metastasis is triggered by chromosomal instability that is caused by continuous errors in chromosome segregation during cell division^[7]. Faults in chromosome segregation cause the rupture of structures in the cell nucleus and the secretion of DNA into the cell fluid, which subsequently activates cellular pathways and signaling^[7].

Cancer occurs after cells are genetically altered to multiply rapidly and indefinitely. This uncontrolled multiplication produces a primary tumor. The cells which make up the tumor eventually undergo changes, resulting in a malignant phenotype (a cancer-causing cell form). This malignancy allows for invasion into the circulation, followed by invasion to a second site for tumor formation^[3].

Diagnosis

Some people already have metastatic cancer at the time of their diagnosis. In these cases, a healthcare provider usually detects metastases during initial testing^[2]. Other people develop metastases after completing treatment for non-metastatic cancer. During routine follow-ups, a healthcare provider checks for signs of recurrence (cancer that comes back after treatment)^[2].

Sometimes when people are diagnosed with metastatic cancer, doctors cannot tell where it started. This type of cancer is called cancer of unknown primary origin^[5].

When observed under a microscope and tested in other ways, metastatic cancer cells have features like those of the primary cancer and not like the cells in the place where the metastatic cancer is found. This is how doctors can tell that it is cancer that has spread from another part of the body^[5].

Healthcare providers may use one or more of the following tests to diagnose metastatic cancer^[2]:

• Biopsy (removing a sample of tissue for testing in a lab)
• Blood tests
• Bone scans
• CT scans (computed tomography scans, which use x-rays to create detailed images)
• MRI scans (magnetic resonance imaging scans, which use magnets and radio waves to create images)
• PET scans (positron emission tomography scans, which use radioactive material to show how organs and tissues are functioning)
• Tumor marker-based tests
• Ultrasound
• X-rays

Treatment

Healthcare providers treat metastasis based on where the cancer started. For example, if a person has breast cancer and the cancer spreads to their liver, their provider will still treat it the same way as breast cancer^[2].

Treatment for metastatic cancer may include chemotherapy, radiation therapy, surgery, immunotherapy, targeted therapy, hormone therapy, or a combination of treatments^[14]. The treatment recommendations you receive depend on the type of cancer you have, how much it has spread and to where, as well as your age and overall health^[8].

Very often, cancer that has metastasized is treated with systemic therapy, which affects the entire body and includes chemotherapy and other medications such as targeted therapies, hormonal therapies, and immunotherapies^[8].

There is a limit to the safe amount of radiation an area of your body can receive during your lifetime. However, another area might still be treated if there is a safe distance between the two radiation sites^[14].

For bone metastasis specifically, common treatments include bone-building medicines that help strengthen the bones and reduce pain. These medicines are given every few weeks through a vein in the arm or through a shot^[12]. Radiopharmaceutical medicines, which contain a low level of radioactive material, may also be used. Once in the body, these medicines travel to the cancer in the bones and deliver the radiation^[12].

In some cases, direct treatment of individual metastatic tumors with surgery or targeted radiation may be used, particularly in cases of oligometastatic cancer, where a patient has only a few, usually small metastases^[11].

Outlook and prognosis

Clinically evident metastasis remains largely incurable with few exceptions, due to acquired resistance of metastatic tumors to existing therapies^[4]. Doctors cannot cure most metastatic cancers, but treatment can help manage symptoms^[2].

In general, when dealing with metastatic disease, it is treatable but not curable^[8]. There are some exceptions—for example, with melanoma and HER2-positive breast cancer, doctors can cure some patients. Some cancers that did not have the best prognoses in the past are now turning into chronic, treatable diseases^[8].

Many cases of metastatic cancer can only be treated, not cured. Common therapies for metastatic cancer are specifically aimed at reducing symptoms and improving quality of life. Many of these treatments can keep the cancer under control for a long time, allowing patients to live with it like a chronic condition^[8].

The possibilities of curative treatment are greatly reduced, or often entirely removed, when cancer has metastasized^[3]. Metastasis is a key element in cancer staging systems, where it represents the “M” in the TNM staging system. In overall stage grouping, metastasis places a cancer in stage 4^[3].

New treatments, such as targeted therapies and immunotherapies, have led to a real transition in survivorship. People can stay on these treatments for many years, which means they can survive for many years^[16]. Recent data shows that people are now living longer after a metastatic breast cancer diagnosis, and treatments keep improving^[21].

Living with metastatic cancer

After a metastatic cancer diagnosis, finding the emotional strength to move forward can be one of the biggest challenges^[21]. Many people report being in shock and disbelief when they first find out they have metastatic cancer. Give yourself plenty of time to process it all and allow yourself to feel your emotions^[15].

People living with metastatic cancer are part of a growing population of individuals who are living longer with advanced cancer than was once possible^[16]. In 2017, researchers at the National Cancer Institute estimated that more than 150,000 women in the United States were living with metastatic breast cancer^[15].

People with metastatic cancer might require treatment for the disease indefinitely, or they might be on and off treatment for the rest of their lives. They will also likely undergo regular testing to identify signs of a recurrence^[16]. With each scan, many people wonder if this is the one that will reveal a recurrence^[16].

People living with metastatic cancer have needs that may differ from those of people who have been treated for early-stage cancers. Examples of these needs include the management of chronic conditions, psychosocial support, caregiver support, financial support, and communication around the goals of care^[16].

Some tips that may help when living with metastatic cancer include^[15]:

• Make sure you are completely comfortable with your medical team. If you feel that a particular doctor is not treating you respectfully or does not have enough experience, do not hesitate to look for a new doctor
• Find support from others with metastatic cancer. A good support group, online or in person, can help you feel less isolated and more hopeful
• Seek out a social worker or counselor for emotional support
• Look into clinical trials for new treatment options
• Keep moving and stay as active as possible
• Focus on what brings you the most meaning and joy

Focus on achievable daily goals, such as attending a child’s soccer game or lunch with a friend. This may help you appreciate the “little” treats in life and keep you focused on the good things^[19]. Be realistic in your goals, accept that you will not always be up for the task, and may need to adjust your goals for the day based on how you feel^[19].

Remember that your goal is for the best possible life despite your cancer’s metastasis. Your doctor wants to help you have your best possible life, and your treatment team has resources to help you live your best^[18].