Metastases

Most often they form in the liver, lungs, bones and brain – depending on the type of cancer. Initially, they often cause no symptoms and therefore go unnoticed. In many cases, the cancer can no longer be cured, but its progression can be delayed and symptoms can be alleviated. Thus, cancer patients often have many good years ahead of them.

Overview: What are metastases?

Metastases are daughter tumors, offshoots or cancerous metastases of a malignant tumor that have spread to the lymph nodes or other organs. Colloquially, one says that the cancer has “spread”. The danger with almost any cancer is that a tumor will not remain confined to the organ in which it originated. It tends to spread and grow into adjacent tissues. In addition, cancer cells can break away from the tumor and travel to other organs of the body through the blood and lymphatic channels. The process of cancer cells spreading in the body is called metastasis by physicians.

A healthy cell, on the other hand, has no tendency to spread outside the organ. Thus, a liver cell always remains in the liver and divides there. The word “metastasis” is derived from the Greek term “metastasis” – it means “settlement” or “migration”.

The malignant tumor cells settle in the “new” organ, continue to multiply and damage the tissue there as well. Then it usually becomes more dangerous, because metastases are treatable in many cases, but the cancer often can no longer be cured. However, doctors now know that the blanket classification “metastases = no longer curable” is not true in all cases. In individuals with few metastases, a cure is often still possible. It depends, among other things, on the type of cancer and the aggressiveness of the tumor. One difficulty for treatment is that the cancer cells of metastases often have different characteristics than those of the original tumor (primary tumor).

Spread of cancer cells – different pathways

Cancer cells have several ways of leaving their site of origin and moving to more distant regions of the body:

• Via the lymphatic vessels (lymphogenic metastasis): The cancer cells first invade the neighboring lymph nodes and form lymph node metastases. From there, they enter the bloodstream and are further transported with the bloodstream to other organs. In this way, distant metastases develop.
• Via the blood vessels (hematogenous metastasis): Cancer cells can also directly invade the wall of a blood vessel that is close to them. They enter the bloodstream, are carried along with the bloodstream and infect a blood vessel at another site – thus they can reach other organs and cause metastases there.
• Via body cav ities (cavitary metastases): Sometimes cancer cells invade body cavities, for example, the chest or abdominal cavity. This may be the case for lung or gastric and colon cancer, respectively. Thus, sometimes the peritoneum is affected by cancer cells.

Metastases – differentiation according to the site of origin

Depending on the site of origin, physicians divide metastases into three groups:

• Local metastases develop in the immediate vicinity of the original tumor. For example, breast cancer can form daughter tumors in its vicinity.
• Lymph node met astases (regional or area metastases): Cancer cells have spread from the tumor to the surrounding lymph nodes. The more lymph nodes are affected, the higher the risk that the cancer cells are already on their way to other organs.
• Distant metastases: The cancer cells have settled in other, more distant organs. For example, in breast cancer, distant metastases often form in the liver, lungs, brain and bones. Prostate cancer often spreads to the bones first, but also to the liver or lungs.

Not all cancer cells have the potential to metastasize. Researchers suspect that only so-called tumor stem cells are able to do this because they can divide sufficiently. But they, too, probably need certain favorable conditions to spread.

Also, not every cancer cell that has broken free from the original tumor makes it to another organ. This is because the immune system usually fights back. It recognizes the cancer cells and tries to eliminate them. But sometimes the cancer cells win. Some can put on a kind of “magic cap” and make themselves invisible to the immune system – so the defense system has no chance and lets the tumor cells pass.

The relatively new immunotherapy also targets this overlooked control mechanism. It does not act against the cancer cells themselves, but intensifies the immune defense in such a way that it recognizes, attacks and eliminates the tumor cells. Immunotherapy already exists for some cancers, such as black skin cancer or a form of lung cancer.

Metastases – frequency and age

It is not possible to precisely quantify how often metastases occur in cancer patients. It also depends on the type of cancer whether and how quickly metastases form. Some cancers are very aggressive, for example certain types of breast cancer, lung cancer or black skin cancer (malignant melanoma). They scatter very quickly. Others, however, grow more slowly, such as colon cancer, certain forms of prostate cancer or white skin cancer. Spinalioma and basal cell carcinoma very rarely metastasize. And if they do, it is late in the course of the disease.

There is no specific age at which metastases are clustered. In principle, cancer metastases can develop at any age: in children, adolescents, adults, seniors with cancer. It is not true that cancer and metastases grow more slowly with age because metabolism is reduced. In addition, more errors in cell division occur with age, which promotes the development of cancer.

Metastases can also affect any gender – boys as well as girls and men as well as women.

Metastases: Causes are cancer cells on the move

The cause of metastasis is that cancer cells can break free from the tumor lattice and move around the body. Whether and when this happens depends on the type and aggressiveness of the cancer. Not every type of cancer is equally dangerous. Often the immune system fails to recognize and eliminate cancer cells. Thus, they spread through the lymphatic or blood channels and reach other organs. They settle there, multiply and damage the tissue.

Depending on the type of cancer, there are “preferred” sites where cancer cells metastasize. It depends on where the original tumor originated and where the blood pathways lead from there.

Which cancers metastasize where?

• Breast cancer: liver, lung, bone, brain
• Prostate cancer: first bone, less frequently liver, lung, brain
• Lung cancer: liver, bone, brain, adrenal gland
• Colorectal cancer: liver, lung, peritoneum, bone
• Black skin cancer: lung, bone, liver, brain

CUP syndrome – metastases but no tumor of origin

In rare cases, people have metastases, but specialists cannot locate the original tumor. CUP syndrome is the technical term for this. It comes from the English: “cancer of unknown primary”, i.e. cancer with unknown primary tumor. Sometimes doctors can draw conclusions about which organ the cells are presumed to have come from by examining the fine tissue of the cells. Then certain properties of the cells match. Often the tumor of origin can still be determined if one searches intensively for it.

There are several theories about how CUP syndrome develops. One assumption is that the cancer is already scattering cancer cells right at the beginning, and at the same time the original tumor remains small. Other researchers assume that the body successfully fought the first tumor focus, but failed to do so with the metastases.

Symptoms: Metastases cause different symptoms

The symptoms of metastases always depend on the organ in which they arise. For example, people with lung metastases have different symptoms than those with bone metastases. Some examples:

• Lung metastases: They often cause no symptoms for a long time, but can cause coughing (including hemoptysis), shortness of breath, shortness of breath and symptoms similar to pneumonia.
• Liver metastases: Loss of appetite, weight loss, general physical weakness and yellowing of the skin (jaundice, icterus) are possible.
• Bone metastases: Symptoms depend on which bones (e.g., cervical, thoracic, lumbar spine, sacrum) have metastasized. For example, there may be pain, bone fractures, sensory disturbances such as tingling or numbness (when metastases press on the nerves), paralysis, or disturbances in bladder and bowel function.
• Brain metastases: Possible symptoms include headaches, neurological deficits (paralysis), mental disorders, epileptic seizures or nausea, vomiting and fatigue due to increasing intracranial pressure.

Metastases: Diagnosis with us

The diagnosis of metastases always begins with a discussion of your medical history, the anamnesis. Often, when we follow up with a cancer patient, we find metastases. But even when cancer is first diagnosed, some people already have metastases – the disease is then already more advanced when it is discovered. Then, immediately after diagnosis, we look for metastases in the lymph nodes and other organs.

For example, we are interested in the following questions:

• What symptoms do you have and since when?
• How pronounced are your complaints?
• Have you strengthened in the past or have there been situations where they have improved?
• Do you have a known history of cancer? If yes: Which and when was it diagnosed?
• Have you already undergone cancer treatments – when and which ones?
• Do you have any other known underlying diseases?
• Is there cancer in your family?
• Are you currently taking any medications, such as cancer drugs or others? If yes: Which and since when?

Your answers already provide us with initial clues as to the reason for your symptoms. This is usually followed by a physical examination. Among other things, we palpate the lymph nodes and check whether they are swollen.

The search for metastases is based not only on your symptoms, but also on whether there is already a known cancer and which one it is. For example, many types of cancer preferentially metastasize to the bones, liver, lungs or brain. There are various examination methods to detect them there. Imaging techniques are usually helpful, for example:

• X-ray examination, such as of the chest – may show lung metastases
• Ultrasound (sonography), e.g. of abdomen and liver – for diagnosis of liver metastases
• Computed tomography (CT) – an X-ray examination that can make metastases visible
• Magnetic resonance imaging (MRI = magnetic resonance imaging): An examination that uses strong magnetic fields. Radiologists create detailed cross-sectional images of various regions of the body. The extent of cancer, as well as metastases, are usually visible on MRI images.
• Scintigraphy: An examination that uses low-level radioactive substances to visualize sites of increased bone remodeling, such as bone metastases. A special camera records the emitted radiation and a computer calculates images from it.
• Positron emission tomography (PET/CT or PET/MR): This examination uses the tracer FDG and is an established method for finding a primary tumor and detecting metastases throughout the body.

In addition, a blood test with the determination of blood values and sometimes also tumor markers provides further information.

Metastases in pathological findings

After a cancer diagnosis, specialists record in the pathology report whether or not a lymph node is affected or you have a distant metastasis. For this purpose, they use the internationally used TNM classification:

• T = Tumor: How big is the tumor and how far has it spread? (T1 to T4)
• N = Node (engl. lymph nodes): Are cancer cells detectable in the lymph nodes? How many are affected? (N0 to N3)
• M = metastasis: Are metastases detectable in organs further away? M0 = no metastases present, M1 = metastases detectable.

The tumor can then be assigned to a stage(staging), on which treatment and prognosis also depend.

Metastases: Prevention, early detection, prognosis

There are no special measures you can take to prevent the development of metastases. It is always important that after a cancer diagnosis without metastases, the first cancer treatment (often with surgery, chemotherapy, radiation) starts as early as possible and you also do not stop the treatments. They often last for several months and you need stamina. Then the chances – depending on the type of cancer – are often good that no metastases will develop in the course.

But even years after surviving cancer, metastases can occur. The general principle is that after five years without a relapse, a cancer is considered cured. However, this is not always true, nor is it true for all cancers. In the case of breast cancer, for example, experts assume a significantly longer period for the risk of recurrence – namely more than 20 years. However, the risk of the cancer returning decreases over time.

Special measures for the early detection of metastases do not (yet) exist. Physicians do not routinely look for metastases with imaging techniques as part of follow-up care. They can read clues from your blood or question you closely about your symptoms. If metastases were already found when cancer was first diagnosed, doctors regularly monitor and control their growth and spread. Metastases can be treated and kept in check, often for a long time.

Course and prognosis in metastases

Lymph node metastases are only an indication that the cancer has already “spread” to other locations. In many cases, however, the disease is then still curable. It is different for distant metastases in other organs. The cancer is then considered advanced and usually no longer curable. However, many physicians today no longer make this “black and white” classification in this way, but there are also many “gray” intermediate levels. If a person has very few metastases, the cancer may well still be curable. In any case, specialists can treat metastases well and bring their growth to a halt – often even for a long time.

The course and prognosis of the cancer are naturally more favorable if there are no metastases yet. The cancer can then be cured in many cases. In the case of distant metastases, life expectancy and survival chances decrease. However, the course and prognosis depend on several other factors, for example:

• The type of cancer – some cancers are very aggressive and continue to grow despite treatment.
• The biological characteristics of the tumor – each tumor has a kind of “fingerprint”. Effective medications are available to curb the growth of some of these traits.
• The number and size of metastases – single and smaller metastases are often well managed by specialists.
• The location of the metastases – sometimes they are so inconveniently located that they impair vital functions or cannot be operated on.
• In how many organs are there metastases? If several organs are affected, the prognosis is less favorable.

Many people can live well for many years despite cancer settling. This is also true because there are effective therapies for metastases that slow down the cancer and stop its progression.

Metastases: Treatment with different strategies

Lymph node metastases are removed when the original tumor is operated on. In certain cases, prophylactic removal of lymph nodes is also necessary to avoid missing so-called “occult” metastases. Another technique is that of sentinel or sentinel lymph node biopsy. This can be marked by procedures and subsequently removed and analyzed. If cancer cells are detectable in this lymph node, all lymph nodes from this region are usually removed.

For metastases, specialists usually use the same therapies as for the original cancer: Surgery, chemotherapy, radiotherapy, drugs and other methods. One difficulty is that the cancer cells of the metastases sometimes do not have the same characteristics as those from the primary tumor. The treatment one chooses depends on which organ (or organs) the metastases are in, how many there are, and how large they are. The main treatment options are:

• Pain management: we use painkillers, for example for bone and brain metastases.
• Radiation therapy: Metastases can be killed using high-energy radiation. Today, radiation can be highly focused and reach metastases in all organs: e.g. the brain, liver, bones or lungs. If the cancer is advanced, then radiation can relieve pain or bleeding that comes from metastases.
• Surgery: We can remove individual metastases that are located in easily accessible areas during surgery. During surgery, tumor embolization is often performed to close the blood vessels supplying the tumor.
• Chemotherapy: We can often shrink or completely eliminate metastases with the help of chemotherapy. Strong cytotoxins, so-called cytostatics or chemotherapeutics, are used. The drugs act throughout the body (systemically) – thus “tackling” metastases in multiple organs at once.
• Hormone deprivation treatment, when cancer cells grow under the influence of hormones, for example in breast and prostate cancer.
• Targeted therapy (“targeted therapy”), when the cancer cells are endowed with certain properties and characteristics. There are some drugs that target these and can stop the cancer.
• Immunotherapy to re-skill the immune system to fight cancer cells, for example in lung cancer, kidney cancer or black skin cancer.
• Heat (thermoablation) and cold (cryoablation) specifically destroy the metastases.
• Radionuclide therapy – a special form of radiation used to reduce the size of bone metastases.