The worst word a patient can expect to hear from their physician is that they have cancer, and worse still is when cancer has “metastasized” or “spread”. Cancers are by no means novel and old papyri from ancient Egypt have described cancers and how they present since antiquity, and despite the advances in medical sciences, the outcome of many cancers remains a grim one.
What is metastasis?
Metastasis is when cancer cells leave the place in which they developed in the body to another, either a neighboring organ, a lymph node or other distal sites in the body via the blood stream or lymphatics, where they continue to grow and produce the same or worse symptoms. This can occur at any time after cancer develops and despite it being an end stage of many cancers, not all cancers metastasize, and some will only grow at their site of origin.
How do cancers metastasize?
Metastasis is a complex biological and chemical process, and despite it being highly associated with cancers, they are not the only diseases that involve metastasis. To simplify how it occurs, we have to understand that cancers divide so quickly that the adherence between cells isn’t well established and they can easily break away the “tissue cement” that hold them together and invade nearby blood vessels or lymphatics, then travel to another site. Cancers demand an enormous amount of energy to provide for their rapid growth, so blood vessels develop specifically for them, and since they are rushed, their walls are so weak that they are easily invaded. The site of metastases isn’t chosen randomly, though, and there is a degree of specificity regarding different cancers. Prostatic cancer, for example, metastasizes mostly to the bones of the vertebral column, while cancers of the gastrointestinal tract metastasize to the liver.
The site of metastasis depends on several factors including:
- Line of drainage of lymphatics: cancers tend to spread by lymphatics more than blood, and lymphatics have a line of drainage. Testicular cancers tend to spread to a group of lymph nodes called the para aortic lymph nodes, while breast cancer tends to spread to the axillary lymph nodes located in your armpit.
- Line of drainage by veins: cancers of the gastrointestinal tract are all drained by a venous system through the portal circulation which ends up in the liver, making it the most common site of metastases.
- Molecular specificity: some cancers are inherently more common to spread to specific sites because of receptors found on such cells. This can be seen in cases of distant metastases.
Most blood metastases spread to four organs, more likely the bones, the liber, the lungs and the brain.
Routes of spread
Cancer has different ways of spreading. It is worth saying here that there is a difference between metastasis and direct invasion. Metastases have to be isolated from the main tumor.
Types of spread include:
- Lymphatic spread: This is the case with most cancers of the carcinoma type and generally the most common way of spread of cancers. Cancer cells first affect a lymph node called the sentinel lymph node, then spread to the others. Lymph nodes are affected in a retrograde manner, which means that groups are affected one after another until reaching the end of the lymphatic system backwards. Since lymph nodes drain specific areas called “territories”, it is possible to locate the main tumor by examining the territory of the affected lymph node.
- Hematogenous (blood) spread: Hematogenous spread is the end stage of lymphatic spread and is the most common route in case of a type of cancers called sarcoma. It is generally more dangerous than lymphatic spread.
- Transcoelemic spread: This way of spread is related to body cavities. The abdomen is lined by a special tissue called the peritoneum and the chests by the pleura. Cancer cells “creep” along those linings to affect other organs within the same cavity. This is commonly seen in case of ovarian cancer that may affect the stomach.
- Perineural spread: This is a rare method that involves spreading of cancer along the nerve fibers. It is seen in some types of parotid gland cancers which may reach the brain via the facial nerve that passes through the gland.
- Canalicular spread: This way of spread is often underestimated and underdiagnosed. It involves the spread of cancer along natural “tubular structures” to reach another organ or another part of the same organ. This can be seen in cases of lung cancer, when the cancer cells move along the airways. Another example can be found in cancers of the bile ductal system.
The relationship between cancer and metastasis
Not all cancers metastasize, and it is very rare for benign tumors to metastasize. Cancers that don’t metastasize are called carcinoma-in-situ. Naturally, this is a stage in all cancers before metastasizing, but some cancers very rarely metastasize, as in the case of basal cell carcinoma which only grow at the face, destroying its structures.
On the other hand, some cancer only present clinically by their metastases and are called occult carcinomas. The reason for this is that the primary tumor is found in a hidden place where it doesn’t produce any symptoms. Examples of these tumors include nasopharyngeal cancer, some types of esophageal cancer and some types of lung cancer. The fact that these tumors mostly present by metastases makes their outcome grim.
Symptoms of metastatic cancer
There are no fixed symptoms for metastatic cancer. What is common is that the overall condition of the patient worsens rapidly after the onset of metastasis. Since metastases behave like the primary tumor they can present by:
- Masses: The patient may feel or notice additional masses either close to the original tumor or in faraway sites. The masses may be unsightly or may cause discomfort, especially if they are located around joints.
- Numbness: If the mass is located on or close to a nerve and enlarges, it will compress the nerve causing a wide variety of symptoms depending on the type of nerve and site. Symptoms include pain, numbness, a burning sensation or weakened muscles if the nerve is motor.
- Bone fractures: The bone is one of the most common sites for metastases and, as a common feature of most metastases, they eat up the bone causing severe weakening and easy fracture.
- Jaundice: Jaundice can result from a multitude of causes and are mostly due to problems in the liver or the bile ducts. Metastases whether in the liver or around the bile ducts can impair liver function or obstruct bile flow, respectively.
- Fever, malaise and a general feeling of unwellness: Cancers secrete various chemical substances that may cause inflammation and fever.
- Loss of weight: Loss of weight is one of the hallmarks of malignancy. Cancers need enormous amount of energy which are mostly not fulfilled by daily meals causing it to eat the body stores of fat and muscles.
Diagnosis of cancer metastases
Cancer is diagnosed by careful history taking and clinical examination. Your doctor will ask you specific questions about the mass including its onset, duration and whether it is associated with other symptoms of cancer. They will then examine you and the mass if present. To diagnose metastasis, however, investigations are needed. Investigations are broadly classified into laboratory tests and imaging modalities.
Lab tests: Laboratory tests in cancer include routine investigations such as a complete blood count (CBC) as well as liver and kidney functions. In the case of metastasis, rapid deterioration may occur. Severe anemia is frequently seen and liver functions including bilirubin level may be affected if the liver is taken by metastases.
Tumor markers: You may have come across the term tumor markers regarding cancer diagnosis. They are chemical substances that are either produced by the cancer cells or other normal cells in response to the cancer. They are sometimes found in non-cancerous conditions and are notoriously bad at diagnosing cancer. Their main advantage is that they are good indicators of the aggressiveness of the cancer, its response to treatment, and its recurrence following successful therapy. A rapid elevation of the levels of some tumor markers can be an indicator of metastasis.
Imaging modalities
The most specific investigations regarding the diagnosis of cancer metastasis is imaging. Many imaging modalities are available including X-rays, which can be used routinely and can show some cancer metastases especially those who are dense enough and those who affect bones.
CT scan: It is a better imaging tool at showing metastases and provide a more accurate localization of the metastases, it can also be used with a contrast dye to enhance its visualization.
MRI scan: It is also a good imaging modality to diagnose metastasis in some types of cancer especially those of the brain and spinal cord.
PET scan: It can also be used. It detects cancer metastases across the whole body by measuring the metabolic activity of cells. Cancer cells consume substances at a much higher rate than normal cells and can therefore appear on PET scan.
Scintigraphy: Scintigraphy is a somehow outdated technique that involves a radioactive isotope into the blood stream, then taking an image of the suspicious site to reveal the presence of metastases. It has largely been replaced and its only current use is in thyroid cancer.
Treatment of metastases
The treatment of cancer involves the combination of surgery, chemotherapy, and radiotherapy. Surgery is generally considered as the best method of treatment of solid tumors and provides the best overall survival in resectable tumors. The presence of metastasis, however, renders surgery difficult or impossible.
Limited metastases especially to the local lymph nodes can be managed by surgery followed or preceded by chemotherapy or radiotherapy, but extensive metastases and those involving vital structures make surgery life threatening and avoiding surgery in those cases becomes the best option to spare the patient needless surgery with its numerous complications. The treatment of any disease does not focus mainly on eliminating the pathology, but on providing the best quality of life for the patient.