The term „metastatic cancer” is widely considered to be synonymous with the terminal, end stage of a neoplastic disease, and though this is often the case, there are also many reports of survivors living for years after their cancer spread. In this article we will try to define how the cancer spreads and what exactly it means for patients.
When cancer spreads?
In the classification of most cancers’ stages, formation of distant metastases will most often represent the most advanced stage, associated with an unfavourable prognosis. However, as has been mentioned many times on our site, cancer is in fact a group of very diverse diseases. In some of them, the cancer dissemination occurs always, by definition. In others, the development of metastases is not necessarily a death sentence for the patient.
In most cases, however, finding that the disease has spread will greatly impact the therapeutic approach, with surgical treatment dominating at early stages, and systemic therapy, such as chemotherapy, hormonal therapy or targeted treatment, will be used more often in metastatic disease. Therefore we believe it is very important to understand what metastases are and how they develop.
How cancers spreads
Cancer metastases can form in many different ways, and there are many potential explanations as to how metastasis occurs. The generally accepted theory says that as a result of successive uncontrolled divisions of cancer cells, the function of proteins that bind cells together is disrupted, facilitating their detachment and dissemination to other organs. Numerous mutations acquired during cancer cells divisions must happen together in one cell in order for it to be able to separate from others and pass through the body’s natural barriers, such as vessel walls.
This is a reason why cancer usually spreads at a late stage, when the primary tumour is already large. This concept has been at least partially confirmed by the finding that cancers with abnormalities affecting proteins that bind cells together metastasize more often and at an earlier stage. However, this theory is probably only a simplification of a much more complex process, the ultimate effect of which is the spreading of cancer cells throughout the body and formation of separate secondary tumours, called metastases, in other organs.
What are 3 ways cancer can spread?
The three main routes for cancer spread include body fluids, especially blood and lymph, the cerebrospinal fluid, and directly within the body cavities.
With the growth of new, pathological vessels stimulated by growth factors produced by the tumour, the blood begins to reach and wash the cancer cells off very quickly. In a healthy body, the lymphatic system is normally used by the inflammatory cells that carry information about different microorganisms attacking our bodies. It also drains excessive fluid from tissues. The system also contains lymph nodes that act a straps for viruses, bacteria and damaged cells, including cancer. Thus, they are also examined for presence of cancer cells, helping to determine whether the disease is metastatic.
The fact that cancer cells disseminate with blood is also important in the process of modern molecular diagnostics. Using genetic material from damaged cells found in the blood, the so-called circulating DNA, a molecular assessment of the cancer can be performed, without the need for a tissue removal, i.e., a surgical biopsy. This process is called a liquid biopsy and is a minimally invasive procedure that allows speeding up the diagnostic process as well as improving the therapy. The fact that there are cancer cells in the blood does not mean that the cancer have formed distant metastases. Usually, additional genetic abnormalities need to occur in the disseminated cancer cells for them to stop at a specific organ and start dividing again, forming a new tumour.
How cancer can spread?
Some cancers, such as leukaemias or lymphomas, develop within the circulatory or the lymphatic system, so by definition they are disseminated right from their onset. Nevertheless, many of them can be effectively treated nowadays, achieving long-term stabilization of the disease or even a complete recovery of the patient.
Cerebrospinal fluid may also be a route of dissemination for tumours involving the brain and the spinal cord. In this case, the examination of the fluid may show the presence of cancer cells, and for some patients this method may be preferred over the direct brain biopsy. Single cases of dissemination via other body fluids, e.g. with urine in case of urinary tract cancers, were also suggested, but they occur very rarely, if not at all.
Another route for dissemination is the spread of tumours within natural body cavities. This can be the pleural cavity or airways in case of lung cancer, or the abdominal cavity for colon cancer or, even more often, ovarian cancer. In the latter case, the most common treatment is an attempt to surgically remove all the metastases, which is sometimes combined with an infusion of a chemotherapeutic agent directly into tche abdomen. This is an exception to the rule that disseminated disease is not treated surgically. Other exceptions include, e.g., removal of single adrenal or liver metastases in lung or colorectal cancer. Such procedures can prolong the patient’s life of or even result in curing the disease in some cases.
Where do cancers spread?
The site where metastasis are formed depends on the location of the primary tumour and the type of cancer the patient is dealing with. The most common sites for distant metastasis via the blood are those organs with best blood supply, such as the liver, lungs, the brain and bones. In turn, the lymphatic system spread involves first the nearest lymph node, collecting lymph from a given area, and then other node groups and organs in the vicinity.
Today, very often surgical procedures to remove breast cancer or melanoma involve a procedure of detecting and removing this node, by applying a dye or a radioactive isotope to the tumour area before surgery. This way, only this lymph node, called sentinel, is removed. Before the sentinel node procedure was introduced, the entire group of lymph nodes was resected during surgeries, resulting in frequent post-surgical complications.
Some cancers, due to the expression of specific proteins, show a predilection for metastases to specific organs, very often located at a great distance from the primary tumour. Lobular breast cancer is a good example here, as it frequently metastasises to locations such as the stomach or the ovaries.
Which cancers spread the fastest?
As already mentioned, cancers such as lymphomas or leukaemias by definition are treated as disseminated tumours from the moment of their diagnosis, and systemic therapy is initiated in their treatment. In other cancers, the risk of metastasis depends on their location, and the degree of tumour aggressiveness, histological subtype and molecular aberrations. Some organs have much better blood supply and/or multiple lymphatic vessels, so metastases will spread very quickly, as it is the case, e.g., with the liver and the pancreas. Aggressive tumours, less similar to tissues from which they originate, metastasize more often and faster. Histological subtypes of some tumours, such as micropapillary carcinomas, are characterized by very high level of discohesion, resulting in their very fast spread to other organs. Loss of proteins responsible for the formation of bonds between cells, as was mentioned before, also increases the risk for cancer dissemination. At the other extreme, there are tumours such as clear cell carcinoma or some types of breast cancer, where distant metastases can appear even after twenty years from the surgical removal of the primary tumour.
In order to assess whether the disease has disseminated, it is necessary to conduct very thorough diagnostics, including radiological imaging, clinical examination, and a microscopic analysis of suspicious lesions and lymph nodes removed during surgery. Additionally, a thorough pathological assessment, especially with the use of molecular methods, allows estimating the risk of metastases formation in those cancers where they are not visible at the time of biopsy. For this purpose, however, a properly equipped laboratory is required.
How cancer can spread? Conclusion
As it can be seen, the formation of cancer metastases is a complex process that is not yet fully understood and that depends on multiple factors. It usually , but not exclusively, occurs in advanced cancers. With the development of modern medicine, a diagnosis of the metastatic disease is no longer synonymous with a death sentence. The key is to choose the right treatment, taking into account the stage of the disease and potentially occurring molecular disorders. This, however, requires professional diagnostics.
Author: Adam Gorczyński, MD, PhD