Treatment

The treatment of CUP depends on the size and location of the tumor, where the cancer has spread, and the patient’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan. Since CUP has usually spread to more than one place at the time of diagnosis, this tumor can rarely be removed surgically or treated with localized radiation therapy. However, CUP may respond well to treatment with chemotherapy, and some tumors can be even fully eliminated.

This section outlines treatments that are the standard of care (the best treatments available) for this specific type of cancer. Patients are also encouraged to consider clinical trials as a treatment option when making treatment plan decisions. A clinical trial is a research study to test a new treatment to prove it is safe, effective, and possibly better than the standard treatment. Your doctor can help you review all treatment options. For more information, visit the clinical trials section.

A description of each treatment option is below, followed by an outline of treatment by CUP subgrouping.

Surgery

A surgeon will perform an operation to remove the tumor and an area of tissue around the tumor (called a margin). The extent and location of the surgery depends on where the cancer is found and its size.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells.
The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation treatment is given using implants, it is called internal radiation therapy or brachytherapy. Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy is delivered throughout the bloodstream, targeting cancer cells throughout the body. The side effects of chemotherapy depend on the individual and the dose used, but can include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea. These side effects usually go away once treatment is finished.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications you've been prescribed, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.

Treatments by CUP subgroup

The following subgroups can often be identified by the initial clinical and pathologic evaluation (see Diagnosis) and have recommended treatments:

Women with adenocarcinoma limited to the axillary lymph nodes. Treatment should follow guidelines for stage II breast cancer, even if no primary site in the breast can be identified. Local treatment should include mastectomy (surgical removal of the breast) or axillary node dissection (surgical removal of the lymph nodes) plus radiation therapy to the breast. Adjuvant treatment (treatment after surgery) with chemotherapy and/or hormone therapy should also be recommended, depending on the number of involved lymph nodes, the estrogen/progesterone receptor status, the HER2 status, and other features of the tumor.

Women with peritoneal carcinomatosis (adenocarcinoma involving the surface of the abdominal cavity). Treatment should follow guidelines for stage III ovarian cancer, even in women with normal ovaries or whose ovaries have been removed. When possible, debulking surgery (initial surgery to remove as much of the cancer as possible) should be performed. Chemotherapy with a taxane/platinum combination should follow surgery, as in ovarian cancer treatment. CA-125 is often a useful tumor marker for monitoring the treatment’s effectiveness. Approximately 20% to 25% of women in this group have long-term survival.

Young men with poorly differentiated carcinoma involving the mediastinum (center of the chest between the lungs) or retroperitoneum (back of the abdominal cavity). Some men in this group may have germ cell tumors, even if the diagnosis cannot be made. Elevated levels of HCG and AFP in the blood strengthen this possibility. Initial chemotherapy should follow guidelines for treatment of advanced testicular cancer. Surgical resection (removal) of the remaining tumor after chemotherapy is often necessary. Cancer can be successfully treated in about 30% of men in this group.

Squamous cell carcinoma involving the cervical (neck) lymph nodes. Even if a careful search does not reveal a primary site in the head and neck, these patients should receive treatment according to guidelines for locally advanced head and neck cancer. This usually includes concurrent (given at the same time) treatment with radiation therapy and chemotherapy. In some patients with small, involved cervical lymph nodes, treatment with radiation therapy alone, or surgery followed by radiation therapy, is sufficient. About 40% to 60% of patients in this group have long-term survival.

Squamous cell carcinoma involving the inguinal (groin) lymph nodes. Local treatment should include a lymph node dissection (removal of all inguinal lymph nodes) or radiation therapy. Chemotherapy given at the same time as radiation therapy should also be considered.

Patients who have only a single metastasis. This includes a broad range of patients, since the single metastasis may be found in any number of locations (for example, lymph nodes, brain, lung, or liver). Depending on the location, treatment should include either surgical removal of the tumor or radiation therapy. Most patients in this group eventually have metastases in other locations, but often after a long time without any disease.

Men with metastases limited to the bones and/or an elevated PSA level. These patients should be treated with hormone therapy, in line with treatment recommendations for advanced prostate cancer.

Patients with adenocarcinoma involving the liver and/or abdomen. In some patients where the tumor spread is limited to the abdomen, special pathology tests suggest that the cancer started in the colon. Patients should receive treatment following guidelines for advanced colon cancer.

Patients with poorly differentiated neuroendocrine tumors. Although the primary site usually remains unknown, these types of neuroendocrine tumors usually respond to chemotherapy with platinum/etoposide (Etopophos), with or without taxane (paclitaxel [Taxol] or docetaxel [Taxotere]). This treatment is effective in shrinking the cancer, with resulting improvement in cancer-related symptoms, in about 60% of patients. A smaller percentage (10% to 15%) of patients in this group have complete shrinkage of cancer with chemotherapy.

Patients with poorly differentiated carcinoma. Patients in this group have tumors of many types, and chemotherapy is sometimes successful. Certain clinical factors (such as tumors located only in lymph nodes, two or fewer areas of metastasis, and younger age) are associated with better outcomes with chemotherapy. Clinical trials should be offered to all patients in this group.

Chemotherapy for those not in a CUP subgroup

For a patient who cannot be classified into any of the subgroups above, highly successful treatment is less frequent. However, many patients can benefit in some way from chemotherapy. Several combinations of chemotherapy have been researched and evaluated in patients with CUP. Usually, these chemotherapy treatment plans contain drugs known to be effective against a variety of cancer types. In particular, combination chemotherapy containing newer drugs have resulted in improved success rates and fewer side effects.

Although curative treatment is only seen in about 5% of patients given chemotherapy, it produces shrinkage of tumors in about 35% to 40% of patients, and 20% to 25% of patients live two years or more. After about four to six weeks of treatment, it is clear which patients are benefiting from treatment; those patients will continue treatment for four to six months. Even for patients whose tumors do not respond to chemotherapy, treatments are available to reduce symptoms.<</p>

All patients with CUP should always ask about the availability of clinical trials evaluating new drugs or drug combinations. Many new drugs are now being evaluated, and it is likely that some of these will improve the treatment of patients with CUP.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: During Treatment.