Bone metastasis or metastatic bone disease is said to occur when cancer cells from other parts of body spread to the bone. After lung and liver, bone is considered to be the third most common organ involved by metastases. In breast cancer, the bone is the second most common site for metastases.
Metastases in the bone need early detection and aggressive management.
How Does Bone Metastasis Occur?
The term metastasis refers to the spread of the cancer cells from their original or primary site to a different location in the body. It must be stressed that local invasive growth is not considered metastases but local spread or expansion of the tumor.
Thus metastasis is the process by which cancer cells migrate throughout the body. However, the cells of the new secondary tumor are similar to the primary tumor
Cells have to break away from the primary tumor and form tumor at some other place in the body [secondary tumor].
Metastatic cancer and stage 4 cancer or advanced are other names for metastases.
However, confusion may occur because of use of the term “locally advanced” cancer which means cancer that has spread to nearby tissues or lymph nodes but not throughout the body.
Metastatic cancer is always described along with its primary tumor. For example breast cancer with bone metastasis.
Sometimes the original or primary tumor remains unrevealed and metastasis is discovered. In such situations, the metastasis is called cancer of unknown primary origin.
The secondary cancer is known by the original one. For example, a lung cancer metastasis into the liver is called metastatic lung cancer and not liver cancer
Metastasis in Greek means displacement. Metastasis is one of three hallmarks of malignant tumors.
Different tumors have different capacity to metastasize.
The cancer cells break away from the main tumor and enter the bloodstream or lymphatic system. Then they can be carried to any part like bones, brain, liver, lymph nodes, and lungs among other tissues.
Primary tumors consist of heterogeneous populations of cells. The cells with genetic alterations are able to surmount physical boundaries, spread, and colonize a distant organ.
Each tissue has a specific milieu where the cancer cells can grow. However, to break and grow at some other place, the cells need to become exposed to environmental stresses, including a lack of oxygen or nutrients, a low pH, and mediators of the inflammatory response. These pressures can select tumor cells with the capability of growth despite these conditions.
The metastatic cells first climb over/around neighboring cells and crawl until they hit a blockage called the basal lamina or basement membrane.
To cross this, the cells make use of digestive enzyme matrix metalloproteases. After crossing basal lamina, they squeeze themselves in between vessel lining cells and float through the circulatory system until they find a suitable location to settle and re-enter the tissues. The cells can then begin to grow in this new location, forming a new tumor.
A malignant cell which has gained the access is not always successful in forming a secondary tumor as it could be killed by the immune system or gets damaged or stuck in blood vessels or lymphatic system. Moreover, the cell may not be able to survive once it leaves its colony or primary tumor.
Routes of Metastasis
There are three primary paths of tumor spread-
- Hematogenous or through blood circulation
- Lymphatic system
- Transcoelomic – Through the body wall into the abdominal and chest cavities
The hematogenous route system is the primary route of spread.
The lymphatic vessels are the main route for spread to the local lymph nodes. From their again, the hematogenous route is taken.
Approximately, 3% of all cancers are of unknown primary origin. In some of these cases, a primary tumor may appear later.
Symptoms of cancer metastasis would depend on the location of the tumor. For example, lymphadenopathy is lymph nodes involvement and hepatomegaly in the liver. Bone metastasis causes weakness of the bone, pain and fracture etc.
- Lymph nodes – lymphadenopathy.
- Lungs – Cough, blood in sputum and shortness of breath
- Liver – Hepatomegaly (enlarged liver), jaundice.
- Bones – Bone pain, fracture of affected bones.
- Brain – Neurological symptoms such as headaches, seizures, and vertigo.
Although advanced cancer may cause pain, it is often not the first symptom.
The metastatic spread to the bone is hematogenous. Therefore, bony metastasis affects vascularised parts especially the axial skeleton.
Presentation and Evaluation of Bony Metastasis
The patient with metastatic bone disease metastases may present by any of the following
- Pathological fracture
- Hypercalcemia of malignancy
- Neurological deficit in case of vertebral involvement
- Detailed clinical history
- A high index of suspicion
- Clinical examination
- Radio imaging – Plain radiographs, CT, MRI as required
- Bone Scan
- Hematological investigations – Would be guided by patient profile
- PTH level
- Serum electrophoresis
- Bence Jones proteins
- Biochemical markers for malignancy
- Chest radiographs
- Skeletal survey
- CT guided biopsy
- Open biopsy
- Special Investigations
- Positron emission tomography is helpful in evaluating response to chemotherapy and treatment guidance.
- Angiography is used in vascular or very large tumors or aneurysmal bone cysts to identify the feeder vessel or embolize it preoperatively.
Treatment of Metastatic Bone Disease
Treatment of bone metastasis is more aggressive than the treatment of the localized tumor.
A multimodal approach using surgery, chemotherapy, radiation therapy and other feasible options [hormone therapies] is considered.
The choice of treatment generally depends on the type of primary cancer, the size, and location of the metastasis, the patient’s age and general health, and the types of treatments used previously.
The treatment options currently available are rarely able to cure metastatic cancer.
Aims of the treatment in metastatic bone disease are
- Pain relief
- Preservation/restoration of the function
- Local tumor control
- Skeletal stabilization
There are three approaches to metastases and role of each would depend on the type of metastatic tumor, location, and extent of metastases.
- Systemic Therapy
- Bone marrow transplant
- Hormone therapy
Radiotherapy is done for suppression of tumor growth and pain relief.
Surgery is done either for removal of tumor or fixation of pathological fractures or to carry out amputation in case of unsalvageable limbs. In case of the joint is destroyed by a tumor or needs to be taken out, endoprosthesis or arthrodesis is considered.