Carcinoma of unknown primary

Definition

Carcinoma of unknown primary (CUP) is a disease in which malignant (cancerous) cells are found in the body, but the organ where they initially began growing, the primary site , cannot be discovered.

Description

The area where a cancer originates in the body is often referred to as the primary tumor. Cancer of unknown primary is a cancer that starts out in an unknown spot and then metastasizes (spreads) to another site, such as a lymph node, the liver, lung, brain, or the bones. Because the primary site is unknown, prognosis may differ from patient to patient.

Most cancers are named after the area of the body in which they start. For example, breast cancer is cancer that originates in the breast. If it spreads to another part of the body, it is still called breast cancer, and the cancerous cells that have metastasized still look like breast cancer cells. With CUP, however, doctors are unable to know with certainty the origin of these cells.

Demographics

According to the American Cancer Society, about 35, 000 cases of cancer of unknown primary are diagnosed each year. These represent approximately 3% to 5% of all cases of cancer. The average age of a patient diagnosed with CUP is approximately 58. The disease is more common in men than in women.

Causes and symptoms

Every cancer has distinct risk factors, or causes. It is difficult to identify specific causes of CUP since the exact type of cancer is unknown.

The symptoms of carcinoma of unknown primary are organ-specific. These symptoms may include:

• Lymphadenopathy, a condition in which the lymph nodes are swollen, firm to the touch, but do not hurt. Cancers frequently spread to the lymph nodes.
• A mass in the abdomen or a feeling of abdominal fullness. This is often caused by a cancer growing in the liver or the spleen, or by a collection of fluid inside the abdomen called ascites.
• Shortness of breath. This symptom may be caused by cancer that has spread to the lungs or from pleural effusion , a build-up of fluid and cancer cells in the area around the lungs.
• Pain in the chest or abdomen. Cancer growth around nerves or tumors pressing against internal organs may cause these symptoms.
• Bone pain. Severe pain may occur when cancer has spread to the bones. Bones that are made weak by the cancer's spread may contribute to fractures. These fractures may result from minor injuries, or even from normal activities, like rolling over in bed.
• Skin tumors. Some cancers start out in organs and spread through the bloodstream to the skin. Skin metastases are sometimes the first sign of spread from a cancer of unknown primary.
• Weakness, fatigue , poor appetite, and weight loss . These generalized symptoms may happen because the cancer has spread to specific organs or systems. Also, some cancers release hormone-like substances into the bloodstream that affect metabolism and cause these same problems.

Diagnosis

The initial step in evaluating a person with cancer is a medical history and general physical exam. These simple steps may suggest the origin of the cancer. If this is not apparent, various imaging tests, blood tests, and endoscopic exams may be used. A biopsy would be performed for routine study under the microscope. The biopsy is the most important of these tests, as it is needed to confirm the diagnosis of cancer. Once the presence of cancer is confirmed, the doctor will then attempt to find its source. Selecting which tests to perform is dependent upon which cancers are likely to occur in a person of the patient's age and gender.

Many of the tests done on a patient with CUP are geared towards finding the primary site. Blood cell counts and blood cell examination will be performed, because changes in the numbers of different blood cell types may suggest that a cancer of unknown primary has spread to the bones. Another type of blood test commonly done at this diagnostic stage is the serum tumor marker, which measures the amount of substances that are secreted by some cancers into the bloodstream. If these substances are present in the blood of patients with CUP, they can provide clues to the origin of the cancer.

The next diagnostic step is usually a biopsy. The samples obtained for the biopsy will undergo various laboratory tests to help place the cancer into a category that will guide the doctor in choosing appropriate treatment. In addition to biopsies, various imaging studies may be performed to produce pictures of the inside of the body. X rays are often done to determine the presence of a mass, but they are not usually useful in finding out what type of cancer is present or in what organ it began. A computed tomography (CT) scan is often done to produce a detailed picture of the inside of the body, and can often depict the amount of cancer spread throughout the body. CT scans also aid in finding primary tumors in the throat, sinuses, pancreas, ovaries, and some other organs. Magnetic resonance imaging (MRI) takes pictures similar to, but more detailed than, the CT scan. Ultrasounds may show which organs have been affected by CUP, but only rarely can they help find the cancer's site of origin.

In order to receive a diagnosis of cancer of unknown primary, the patient must have had the following done in an attempt to find the origin:

• complete medical history and physical exam
• complete blood cell count and routine blood chemistry tests
• biopsy of the metastatic tumor with a microscopic examination of the cancer cells, along with certain other tests
• if the tumor is found in the abdomen or in the lymph nodes of the groin, a chest x ray and CT scan of the abdomen and pelvis
• ultrasound of the testicles (in males) or pelvis (in females)
• mammogram
• routine testing of the urine
• testing of the stool for blood, which may indicate cancer of the digestive system
• examination of the gastrointestinal (GI) tract
• thyroid scan

If all of these examinations are done, and the primary tumor site is still undetermined, then the patient is given the diagnosis of carcinoma of unknown primary. Based on the cancer's location and classification, doctors will determine which additional tests should be performed.

Treatment team

The patient's primary physician as well as an oncologist will be involved in the care of a patient with CUP. Nurses of various specialties, including those who provide chemotherapy , will be involved. Because of the unique nature of this disease, a pathologist plays a central role in making a diagnosis. There is probably no more important clue to diagnosing a CUP than a thorough evaluation of a specimen. These evaluations provide guidance for the decisions that follow by the oncologist and primary physician.

Clinical staging, treatments, and prognosis

Most types of cancer are placed in stages I, II, III, or IV. These stages are based on the extent of spread and whether or not the cancer has moved to lymph nodes or other organs. Each stage classification is slightly different for each type of cancer. Stage I is the least extensive, with the best prognosis (outlook), and Stage IV cancers have the worst prognosis with the most spread. It is impossible to stage cancers of unknown primary accurately because the type of cancer is unknown. However, in order for it to be considered a CUP, the cancer must have spread beyond the primary site. Therefore, all CUP's are considered a stage IV cancer.

Many different treatments are used either alone or in combination to treat cancer of unknown primary. Some of the treatments include surgery, radiation therapy , chemotherapy, and hormone therapy. Surgery is commonly used to treat CUP. A surgeon may remove the cancer as well as some of the healthy tissue around it. Radiation therapy uses x rays or other high-energy rays to kill cancer cells and shrink tumors. It may be used alone or before or after surgery. Radiation for CUP may be given in two ways—externally or internally. The most common radiation treatment for CUP is given from a machine outside the body. The patient is normally treated five days a week for several weeks. Chemotherapy uses drugs to kill cancer cells. It is a systemic treatment, since it travels throughout the body by the bloodstream. The most common drugs used to treat cancer of unknown primary are:paclitaxel , etoposide , cisplatin or carboplatin , bleomycin , vinblastine , fluorouracil , and ifosfamide .

Several factors are considered when determining which treatment to use for CUP. Although many cancers of unknown primary cannot be cured, treatment may help the patient to live longer or improve the quality of life. Patient and doctor should discuss potential benefits of treatment as well as possible side effects.

The general prognosis for patients with CUP is poor. As a group, the survival rate is around three to four months with less than a 25% survival rate one year after diagnosis, and a 10% survival rate after five years. Although the majority of cancers of unknown primary are resistant to treatment, there are certain types of CUP that have a much better outlook. These subgroups respond better to treatment and reemphasize the importance of the pathologist in evaluating the cancer cells. When cancer of unknown primary has spread to multiple internal organs, the five-year survival rate after diagnosis is at approximately 5%. There are several reasons for the serious prognosis of CUP. Most of these cancers spread rapidly. In addition, it is difficult to know what treatment will be the most effective since the exact type of cancer is not known. Finally, a cancer of unknown primary has already spread beyond its original site by the time the diagnosis is made.

Alternative and complementary therapies

Since most cases of CUP have a poor prognosis, even with the use of traditional treatment, many patients with CUP may be interested in seeking out alternative and complementary therapies. The most commonly sought out alternative therapies include dietary treatments, herbs, homeopathy, hypnotherapy, meditation, vitamins , relaxation and spiritual healing. Many complementary therapies like music and massage, meditation, and herbal teas to relieve nausea are well documented in their abilities to relieve stress and enhance feelings of well being. At the same time, however, it is important to realize that many proposed remedies have not been studied, and may even contain potentially harmful ingredients. Herbs have become very popular, but many have harmful interactions with other medicines. It is important for a patient interested in alternative treatments to discuss this decision with health care professionals.

Coping with cancer treatment

No one can predict how a patient will respond to treatment. Many factors impact how a patient will cope, including a strong family support system, a healthy immune system, or a deep religious faith. Cancer treatment can cause great fatigue. Patients should allow time to recover without feeling the need to resume normal activities immediately. Eating a healthy, balanced diet and slowly increasing activity will help a patient with CUP regain strength and energy.

Clinical trials

Research regarding the nature and treatment of cancer of unknown primary is being conducted in several areas. New chemotherapy drugs, drug combinations, methods of administering chemotherapy, and the effect of peripheral stem cell transplantation on CUP are currently under study. In addition, gene therapy is also being tested as a treatment for CUP. Other approaches under examination include sensitizing the body's immunologic T-cells against cancer cells, as well as using vaccines . Since CUP is a term for several different types of cancer, an improved overall understanding of cancer can help the medical community create improved treatments. One of the ways this happens is through participation in clinical trials . The patient with cancer of unknown primary can find out what clinical trials are available by contacting the National Cancer Institute.

Prevention

Since the exact type of cancer involved in CUP is not known, it is difficult to say just how that cancer might have been prevented, if at all. The risk factors are difficult to identify. Autopsy studies, however, can be of assistance. Patients who have died of CUP show that many of the cancers began in the pancreas, lungs, kidneys, throat, larynx, or esophagus. Smoking is a significant risk factor for each of these cancers.

Other sites of CUP include the stomach, colon, or rectum. High-fat dietary habits are linked to these cancers. Fresh fruits, vegetables and high-fiber foods offer the greatest dietary protection. Another source of CUP is a type of skin cancer termed malignant melanoma . Its primary risk factor is unprotected exposure to the sun.

Special concerns

The inability to identify a primary site for metastatic cancer can generate a great deal of anxiety, anger and frustration for patients and family. They may believe that the physician is incompetent or that the prognosis would be improved if a primary site could be definitively identified. Though it is important to do necessary diagnostic testing, it is common for patients and families to encourage a physician to keep testing well beyond the point in which the primary tumor is likely to be discovered. At this stage, the presence of metastatic tumors indicates that the cancer has already spread, and it is important to start treatment as soon as possible.

Resources

BOOKS

Buckman, Robert, Dr. What You Really Need to Know About Cancer: A Comprehensive Guide for Patients and Their Families. Baltimore: Johns Hopkins University Press, 1997.

PERIODICALS

Cassileth, Barrie R. "Evaluating Complementary and Alternative Therapies for Cancer Patients." CA: A Cancer Journal for Clinicians (November/December 1999): 353-61.

Ward, Darrell. "The Case of the Missing Primary." Frontiers (Spring/Summer 1999): available at <http://www.osu.edu/units/cancer/frontier.htm>.

ORGANIZATIONS

American Cancer Society. (800)ACS-2345. <http://www.cancer.org>.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4-CANCER. <http://www.nci.nih.gov>.

OTHER

National Coalition for Cancer Survivorship 8 June 2001 <http://www.cansearch.org>.

Deanna Swartout-Corbeil, R.N.

KEY TERMS

Chemotherapy

—The treatment of disease by means of chemicals that have a specific toxic effect on the disease-producing microorganisms or that selectively destroy cancerous tissue.

Metastasis

—The process in which cancer cells travel or spread from their original site to other parts of the body.

Primary site

—The area in the body where a cancer originates.

QUESTIONS TO ASK THE DOCTOR

• What treatment choices do I have? Which do you recommend, and why?
• What side effects from treatment can I expect, and what can I do to help reduce them?
• What are the chances that my CUP will return once I am in remission?