discovery
Metastasis is when cancer moves from its original site to another

Cancer metastasis

Key points:

  • Metastasis refers to cancer that has spread beyond its original site.
  • Cancer can metastasize to almost anywhere in the body, though different cancer types normally result in metastases to certain sites (e.g. breast to bone).
  • The percentage of cancers that are metastatic at diagnosis varies hugely, from 5% for breast cancer up to 85% for stomach cancer.
  • There are treatments for metastatic cancer though they are typically systemic (e.g. chemotherapy) and therefore less effective than radical local therapies such as surgery or radiotherapy that are used when cancer is contained to a single site.
  • The process of metastases is extremely complicated and poorly understood.

Metastasis is the word used to describe cancer that has moved from its original site to somewhere else in the body. Doctors often refer to this movement as “metastatic cancer” or “Stage 4 cancer”.

Metastasis is the deadliest aspect of cancer, with an estimated 90% of cancer deaths coming from cancer that has metastasized.[1]   

 

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How Cancer Cells Move

The way in which cancer moves is complicated, but in broad terms cancer travels to new locations in three main ways. Cancers don’t obey the normal rules of cellular growth:

  1. Cancer cells grow directly into tissue surrounding the original tumor;
  2. Cancer cells enter the bloodstream and use it to get to distant locations; or
  3. Cancer cells use the lymph system to travel to other lymph nodes, which can be near or far from the original site.

Common Sites of Cancer Metastasis

Nearly all types of cancer can metastasize (except for blood cancers, which are already systemic) and cancer cells can spread to almost any part of the body. That said, different types of cancer tend to move in certain ways. For example:[1] 

Cancer type Common sites of metastasis
Breast Bone, lung, liver, brain
Prostate Bone, liver, lymph nodes, lung
Lung Bone, liver, adrenal glad, brain
Colorectal Liver, lung, peritoneum
Liver Peritoneum, lungs, bone
Stomach Liver, lung, peritoneum

 

Are Cancer Metastases the Same Type of Cancer?

In short, yes. Cancer that has metastasized to a new site is still referred to by the name of the original cancer site. Thus, breast cancer that has spread to the lungs is called metastatic breast cancer even when referring to the tumors in the lungs. It is treated as a breast cancer with drugs that are effective against breast cancer. If a biopsy was taken it would have the microscopic features of a breast cancer.

Prevalence of Metastasis in Cancer

The prevalence, at diagnosis, of metastases varies by cancer type, largely because certain cancers tend to only cause symptoms, and therefore lead to diagnosis, once they are well developed and have metastasized.[2]

Cancer type % of cases at diagnosis No. of deaths per year worldwide
Metastatic breast 5 522,000
Metastatic prostate 6 307,000
Metastatic colon 24 694,000
Metastatic liver 28 746,000
Metastatic lung 61 1,600,000
Metastatic stomach 85 723,000

 

"Metastases are mostly treated using the same treatments that are used for the original cancer. "

Five Year Survival Statistics for Metastatic vs Non Metastatic Cancers

To illustrate just how problematic metastases are it is helpful to compare five year survival rates for metastatic vs non metastatic cancers by type:

Cancer type Non-metastatic Metastatic
Prostate 100 29
Breast 99 23
Colon 90 12
Stomach 62 4
Lung 52 4
Liver 28 2

Thus cancers that are typically detected whilst localized (for which there are effective screening programs, such as prostate and breast cancer) tend to result in earlier diagnoses, have much better outcomes, due to effective local treatments, and therefore also have impressive survival rates.

How are metastases diagnosed?

There is no one test for metastases and so a variety of tests will normally be performed depending on cancer type and presentation. For example, a bone scan may be used in the case of metastatic prostate cancer (because that is by far the most common site that prostate cancer spreads to). Other types of scans are also common (MRI, PET, CT, etc).

It is also possible to use blood tests – called tumor or cancer markers – for certain types of cancer after diagnosis. If levels rise then it can be an indication that the cancer has recurred locally or metastasized. The good example of this is in prostate cancer after the prostate has been removed. Prostate cells (both healthy and cancerous) produce a protein called prostate specific antigen (PSA) – once the prostate has been surgically removed, PSA levels should fall to zero. Detectable PSA levels normally mean the cancerous cells that were in the prostate avoided the surgeon’s scalpel and are present locally (in the prostate bed) or have metastasized to other body locations. The rate of the change of the PSA level (known as doubling time) can help decide whether the cancer has recurred locally or has metastasized.

Other types of helpful blood tests include:

  • Ovarian cancer: CA-125
  • Colon cancer: Carninoembryonic antigen (CEA)
  • Testicular cancer: Alpha feto protein (AFP) and Beta HCG

How Is Metastatic Cancer Treated?

The reason why metastatic cancer is so lethal is that the available treatments for such tend not to be curative. Cancer is most easily treated when it is confined to a single location where treatment options like surgery and radiation are effective (you can read more about cancer treatment here INSERT LINK). However, once cancer has metastasized to other parts of the body systemic treatments such as chemotherapy and hormone therapies (in breast, ovarian and prostate cancers) need to be used and they tend to be less effective.

Metastases are mostly treated using the same systemic treatments that are used for the original cancer. Thus a breast cancer patient with metastasis in the lungs will normally be treated with the same drugs as a breast cancer patient (with similar subtype) who has no metastases. Other, more targeted therapies, such as radiation or gamma knife surgery (a type of radiation) may be used to treat specific metastasis sites.

Metastases and the Stem Cell Theory of Cancer

One particularly interesting facet of metastases is that the cells that metastasize undergo changes that make them look more like so-called stem cells. This is known as the epithelial to mesenchymal transition (EMT).

EMT occurs during normal development and also in would healing. In other words, it is a natural bodily process used for growth. It appears that metastatic cancer cells hijack this ability for their own nefarious benefit.

Cancer cells that have metastasized therefore look a lot like stem cells, which provides evidence for the theory that it is only a small subset of cancer cells (called cancer stem cells) that in fact have the ability to replicate endlessly. If correct, and it’s important to understand that the evidence is preliminary and unclear, then this has important implications for treatment. For example, certain drugs are effective against stem cells but not precursor cells. An example is salinomycin, which kills metastatic cancer stem cells but not other epithelial cells.

Although beyond the scope of this introductory article, there is other evidence for the cancer stem cell theory. For example, when cells from a tumor are transferred between animals only a very few of them (0.1% to 0.0001%) form new tumors, and the cells with that capacity carry surface proteins that are also found on stem cells.[3]

John Hopkins University, Introduction to Cancer Biology (available at: https://www.coursera.org/learn/cancer) (includes discussion on mestastases)
John Hopkins University, Introduction to Cancer Biology (available at: https://www.coursera.org/learn/cancer) (includes discussion on mestastases)
Hesketh, Introduction to Cancer Biology, Cambridge University Press, 2013, pgs142-143

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