Cancer - Unknown Primary

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Treating Cancer of Unknown Primary TOPICS

Treatment of specific instances of a cancer of unknown primary

The types of treatment used for a cancer of unknown primary depend on several factors, including the size and location of the cancer, the results of lab tests, and how likely it is to be a certain type of cancer. Your overall health and ability to tolerate treatment matter also. Of course, if the origin of the cancer can be determined during testing, the cancer would no longer be an unknown primary and would be treated according to where it started.

Squamous cell carcinoma in lymph nodes in the neck

Often these cancers began somewhere in the mouth, throat, or larynx. They are often treated with surgery and/or radiation therapy.

Surgical treatment removes lymph nodes and other tissue from the neck. This operation is called a neck dissection. There are several types that differ in the amount of tissue removed from the neck:

  • A partial or selective neck dissection removes only a few lymph nodes.
  • A modified radical neck dissection removes most lymph nodes on one side of the neck between the jawbone and collarbone, as well as some muscle and nerve tissue.
  • A radical neck dissection removes nearly all the nodes on one side, as well as even more muscles, nerves, and veins.

The most common side effects of any neck dissection are numbness of the ear, weakness in raising the arm above the head, and weakness of the lower lip. These side effects are caused by injury during the operation to the nerves that supply these areas. After a selective neck dissection, the weakness of the arm and lower lip usually go away after a few months. But if a nerve is removed as part of surgery, the weakness will be permanent. After any neck dissection, physical therapists can show the patient exercises to improve neck and shoulder movement.

Radiation therapy might be used instead of surgery. One potential advantage is that the area treated would include both the nodes with metastatic cancer and several of the areas of the neck likely to contain a primary tumor.

Some patients are treated with both surgery and radiation therapy. This is considered when large and/or many tumors are present. The radiation may be given before or after surgery.

When tumors are very large or present on both sides of the neck, chemotherapy (chemo) and radiation therapy are often used together. Cisplatin and 5-FU with a taxane [docetaxel (Taxotere) or paclitaxel (Taxol)] are the usual chemotherapy drugs used. Cetuximab (Erbitux) may also be used with radiation (instead of chemo).

The outlook for these patients depends on the size, number, and location of the lymph nodes containing metastatic cancer. For more information about the usual treatments for these cancers see our documents, Oral Cavity and Oropharyngeal Cancer and Laryngeal and Hypopharyngeal Cancer.

Adenocarcinoma in lymph nodes under the arm

Because most cancers that have spread to the axillary nodes (lymph nodes under the arm) in women are breast cancers, the recommended treatment is similar to that for women diagnosed with breast cancer that has spread to these nodes.

Surgery to remove axillary nodes (called an axillary lymph node dissection) is done, and the breast on the same side may be treated with mastectomy (surgery to remove the breast) or radiation therapy.

Depending on the woman’s age and whether the cancer cells contain estrogen and/or progesterone receptors, additional (adjuvant) treatment may include hormonal therapy (with tamoxifen or an aromatase inhibitor), chemo, or both. The cancer can also be tested for a protein called HER2. If positive, drugs that target the HER2 protein such as trastuzumab (Herceptin) and lapatinib (Tykerb) may be used. For more information about prognosis and treatment of breast cancer that has spread to the lymph nodes, see our document, Breast Cancer.

Although cancer in axillary lymph nodes in men may represent spread from a breast cancer, spread from a lung cancer is much more likely. An axillary lymph node dissection and/or radiation therapy to the underarm area may be considered in some cases, but many doctors would recommend chemo first and waiting to see how the enlarged lymph nodes respond. The combination of drugs would probably be the same as that given for adenocarcinomas or poorly differentiated carcinomas found in other parts of the body.

Cancer in groin lymph nodes

It’s important to search carefully for the origin of these cancers, as many of them can be treated effectively if it is found. If the primary tumor can’t be found, surgery is usually the main treatment.

If the cancer appears to be confined to a single lymph node, removing it may be the only treatment. In other cases, more extensive surgery (a lymph node dissection) may be needed. If more than one lymph node is found to contain cancer, radiation therapy and/or chemotherapy may be recommended as well.

Women with cancer throughout the pelvic cavity

Unless tests have found a primary cancer outside the ovaries (in which case the diagnosis of cancer of unknown primary would no longer apply), these cancers are most likely to be spread from either ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma (PPC). Fallopian tube cancer and PPC are diseases similar to ovarian cancer and they are all treated the same way.

Treatment is typically surgery to remove the uterus, both ovaries, both fallopian tubes, and as much of the cancer as possible. After surgery, 6 to 8 months of chemo is recommended, usually with a taxane (paclitaxel or docetaxel) and platinum drug (cisplatin or carboplatin). For more information, see our document called Ovarian Cancer.

Cancer in the retroperitoneum (back of the abdomen) or mediastinum (middle of the chest)

If lab tests of the tumor sample have ruled out lymphoma, the most likely diagnosis (particularly in younger men) is a germ cell tumor. Even cancers in these areas that do not have lab results typical of germ cell tumors often respond to chemotherapy combinations for treating testicular germ cell tumors. Chemo drugs used include cisplatin and etoposide, sometimes with bleomycin or ifosfamide. More information about the treatment of germ cell tumors can be found in our documents, Testicular Cancer and Ovarian Cancer.

If a carcinoma is in the mediastinum in an older patient it may be treated as a non-small cell lung cancer.

Melanoma in lymph nodes only

Once a cancer of unknown primary (CUP) has been diagnosed as a melanoma, it’s no longer a true CUP. This situation is mentioned, nonetheless, because some tests to identify melanomas may take several days. Until they are complete, these patients are considered to have CUP.

The recommended treatment of melanoma of unknown primary is surgery to remove the lymph nodes in the affected area. If spread to other nodes becomes apparent at a later time and all of the cancer can be removed, these nodes are also removed. Doctors may also give a drug called interferon that may slow the return of melanoma. The main side effect of this drug is flu-like symptoms, including fatigue. For more information see our document, Melanoma Skin Cancer.

Cancer in other locations such as bone or liver

This group represents the majority of people with CUP. Usually the cancer is in the bones, lung, or liver. Once lab testing of the biopsy specimen has excluded cancers of the breast, prostate, thyroid, and lymphoma (all of which often respond well to specific treatments), many of the remaining patients are treated with chemo to try to shrink the tumor and reduce symptoms.

Most doctors use a standard chemotherapy regimen. It consists of either cisplatin or carboplatin, combined with a taxane drug such as paclitaxel or docetaxel. Other drugs like gemcitabine may be used as well. It’s important to stop chemo if it’s not working to relieve symptoms or shrink the cancer, as the side effects of these drugs can be severe and impair quality of life.

Sometimes chemo can be quite helpful. About 15% of patients treated with aggressive chemo will have a complete response (with no visible cancer left after treatment), and in some of these the cancer stays away for years.

Patients in poor health who would not be able to tolerate the side effects of aggressive chemo are sometimes treated with lower doses or with drugs that cause fewer side effects. But the benefit of this approach is not clearly proven. Another option is to focus on relieving symptoms as they occur. Many patients with cancer spread to bones benefit from treatment with bisphosphonates (discussed in the section “Other drugs for cancer of unknown primary”). These drugs can help strengthen bones weakened by cancer, preventing fractures (breaks), and reducing pain.

Some poorly differentiated small cell cancers of unknown origin can shrink dramatically using chemo combinations originally developed to treat small cell lung cancer. The benefit usually lasts for several months, but these cancers almost always return.

Some neuroendocrine cancers may respond to treatment with octreotide (Sandostatin). This drug may be able to slow or stop growth for some time. The tumors most likely to respond are the ones able to be seen on somatostatin receptor scintigraphy (imaging).

More information about treatments for cancers that have spread can be found in our document Advanced Cancer.


Last Medical Review: 03/12/2013
Last Revised: 01/31/2014