Metastasis Health Article

Diagnosis and monitoring of metastases

Some primary cancers, such as lung and ovarian cancers, begin to shed tumor cells that form metastases elsewhere in the body before the primary cancer is large enough to be detected by standard diagnostic techniques. Marker molecules that are given off by micrometastases circulating in the bloodstream can now be detected.

Tumor markers are substances produced either by tumors themselves or by the body in response to a tumor. The blood levels of tumor markers can be used to evaluate the recurrence or spread of cancer and the patient's response to treatment. Some commonly used tumor markers include: prostate-specific antigen (PSA) for prostate cancer; prostatic acid phosphatase (PAP) for prostate cancer that has metastasized, testicular cancer and leukemia; and CA 125 (Cancer antigen 125) for recurrence of ovarian cancer and also to detect cancers of the uterus, liver, pancreas, colon, cervix, lung, and digestive tract; as well as several others.

DNA analysis can be used to distinguish metastatic tumors from multicentric tumors. A multicentric cancer is one that appears simultaneously in several different parts of the body, as distinct from cancers with primary and secondary (metastatic) tumors. Mutations in the p53 tumor suppressor gene have been used as "genetic fingerprints" to identify differences between multicentric and metastatic tumors.

Some specific types of metastases

Brain

SYMPTOMS.

Metastatic tumors to the brain usually come to the doctor's attention in the same way as primary tumors—they cause increased pressure inside the head, disturbances of brain functions, or both. Common symptoms of brain metastases include headaches, seizures, loss of sensation or balance, or personality changes.

SOURCES.

The most common source of brain metastases is primary cancer of the lung. Other primary sources include malignant melanomas and cancers of the breast, kidney, or digestive tract.

DIAGNOSIS.

Secondary brain tumors are usually detected on either CT scans (computed tomography scans) or MRI studies (magnetic resonance imaging).

TREATMENT.

If the patient has only one secondary tumor in the brain, it is sometimes possible to remove it surgically and then treat with radiation. Otherwise, radiation is used by itself to treat the tumors. Steroids may be given to reduce or lower swelling of the brain, treating the headaches and other symptoms. Chemotherapy has only a limited role in treating brain metastases, because most chemotherapy drugs cannot cross the blood-brain barrier. However, intrathecal chemotherapy (chemotherapy drugs injected directly into the spinal fluid) can have a role in treating brain metastases. Patients with multiple metastases in the brain or widespread cancer elsewhere in the body have a very poor prognosis. Treatments that are still under evaluation include laser-assisted surgery and biological response modifiers.

Bone

SYMPTOMS.

Primary bone cancers are less common than bone metastases. Bone metastases, in fact, are a common cause of pain in many patients with late-stage cancer. Metastases in the spine can compress the spinal cord and damage the nervous system. Bone metastases also make bones easier to fracture.

SOURCES.

Breast, lung, and prostate cancer are responsible for about 80% of bone metastases; and over half of patients with these three types of primary cancer will develop bone metastases. Patients with lung cancer that has metastasized to bone live on average less than six months, but breast and prostate cancer patients may have lengthy periods of survival with bone metastases.

Bone metastases are usually caused by tumor cells carried through the bloodstream, and are typically multiple. About 70% of bone metastases occur in the ribs, spine, sacrum (lowest portion of spine, attached to pelvis), or head; most of the remainder occur in the long bones of the body.

DIAGNOSIS.

Bone metastases are usually detected by bone scans, CT scans, or MRIs, and confirmed by a biopsy.

TREATMENT.

Bone metastases are treated with hormonal or systemic chemotherapy and/or radiation therapy. Metastases in the spine may require surgical removal of part of the vertebrae (laminectomy) followed by radiation treatment to prevent compression of the spinal cord. Surgery may also performed if there is a risk of fracture.

As of May 2001, two new drugs show promise as treatments for bone metastases. One is a generic drug called clodronate, which is taken by mouth, and the other is a medication called Atrasentan. Atrasentan was tested on patients in advanced stages of bone metastases who were no longer responding to other forms of treatment.

Lung

SOURCES.

Metastatic tumors in the lungs may result either from primary cancer of the lung or from malignancies elsewhere in the body that spread to the lungs through the circulatory system or by direct extension. The incidence of metastatic cancer to the lung is six in 100, 000 people. Almost any type of cancer can metastasize to the lung, but the most common tumors that spread to the lung are breast cancer, sarcomas, non-Hodgkin's lymphoma, neuroblastoma, and Wilms' tumor. Between 20% and 54% of patients dying of cancer are found to have metastases in the lungs.

DIAGNOSIS.

Diagnosis is usually the appearance of a group of masses on a chest x ray. Evaluation of lung metastases is first directed at diagnosing/locating the primary tumor.

TREATMENT.

Secondary lung cancers are treated primarily by appropriate systemic therapy for the primary tumor. Surgery for secondary lung tumors may be beneficial if there are four or less metastases. Surgical removal of tumors metastatic to the lung is usually performed only if: the primary tumor is treatable, all metastases can be removed, chemotherapy or other nonsurgical approaches cannot be used, and if there are no metastases elsewhere in the patient's body. If the primary cancer is a malignant melanoma, and there is only one secondary tumor, surgery may be an option. (Surgery is usually not done if the primary cancer is a malignant melanoma and there is more than one secondary tumor.) The five-year survival rate for surgical treatment of secondary tumors to the lung is 20%-35%.

Liver

The most common form of liver cancer is metastatic; in fact, metastases in the liver are often the first noticeable evidence of a primary cancer located elsewhere in the body. In the liver, finding multiple metastases is more common than finding a single tumor. The liver's important role within the circulatory system makes it a common stopping point for tumor emboli carried in the blood from other organs.

SOURCES.

The most common sites of primary tumors that metastasize to the liver are the lungs, breasts, colon, pancreas, and stomach.

DIAGNOSIS.

The diagnosis of metastatic liver cancer is usually difficult unless the patient's primary tumor is in advanced stages of disease. Ultrasound, CT scans, and liver function tests are used to screen patients with a known cancer for metastases in the liver, but the results are not fully reliable. A definitive diagnosis depends on biopsy of liver tissue.

TREATMENT.

As of 2001, metastatic cancer to the liver is considered incurable. Systemic chemotherapy may temporarily shrink tumors in the liver and extend the patient's life span but does not cure the cancer. Radiation treatment may relieve pain but is not otherwise helpful. Some doctors may recommend surgical removal of liver metastases, particularly if the primary tumor is in the colon and there is a solitary metastasis, but others do not favor this approach. The five-year survival rate for surgical removal of liver metastases is 20%-30%.

Metastatic cancers of unknown primary origin

Between 0.5% and 7% of all cancers are carcinomas of unknown primary origin, or CUPs. The patient's history and physical examination should be analyzed for signs of breast, prostate, pelvic, rectal, and gastrointestinal cancers. The pattern of spread of a CUP may indicate whether the primary tumor is above or below the diaphragm; lung metastases are twice as common with primary tumors found to be above the diaphragm, while liver metastases are more common if the primary site is below the diaphragm.

Metastases of unknown primary origin are usually treated by chemotherapy— either cisplatin/carboplatin, doxorubicin or paclitaxel. In most cases, the patient's prognosis is poor; the average length of survival is three to four months, with fewer than 10% of patients surviving five years. Male sex and involvement of the liver are negative factors in the prognosis.