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Unknown Primary - Introduction

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will find some basic information about this disease and the parts of the body it may affect. This is the first page of Cancer.Net’s Guide to Cancer of Unknown Primary. To see other pages, use the menu. Think of that menu as a roadmap to this full guide.

What is cancer?

Cancer is a group of more than 100 different diseases. Cancer begins when healthy cells change and grow out of control, forming a mass called a tumor. A tumor can be cancerous or benign. A cancerous tumor is malignant, meaning it can grow and spread to other parts of the body. A benign tumor means the tumor can grow but will not spread.

It is usually fairly easy for doctors to figure out where a cancer began, known as the primary site, and identify any secondary or metastatic site if the cancer has spread. No matter where the cancer spreads, it is still named after the area of the body where it began. For example, breast cancer that has spread to the brain is called metastatic breast cancer, not brain cancer.

What is cancer of unknown primary?

For about 2% of people diagnosed with cancer, the cancer is found at a secondary site, but routine testing cannot help doctors identify where the cancer began. These cancers are called carcinoma of unknown primary site or cancer of unknown primary (CUP).

For some people, specialized testing can eventually help identify the primary site. However, sometimes the primary site cannot be identified. This may be because:

  • The primary tumor is still very small.

  • The body caused the primary tumor to shrink or disappear.

  • The primary tumor was removed during a previous surgery for another condition, such as the removal of a mole on the skin or surgery to remove a woman’s uterus, known as a hysterectomy.

The next section in this guide is Statistics. It helps explain how many people are diagnosed with this type of cancer and general survival rates. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Statistics

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will find information about the number of people who are diagnosed with CUP each year. You will read general information on surviving the disease. Remember, survival rates depend on several factors. Use the menu to see other pages.

CUP is estimated to account for around 2% of all cancer diagnoses in the United States. This means about 33,770 patients will be diagnosed in 2017. The exact number of people diagnosed with CUP each year is not known because some cancers start out being classified as unknown primary, only to have the primary cancer found later. In other cases, the treating physician makes an educated guess as to the site of origin, based on clinical features and x-ray results, and treats the patient for the presumed diagnosis. As new tests that can more accurately determine where a cancer started become available, the number of people diagnosed with CUP will continue to decrease.

People diagnosed with CUP are a diverse group, and prognosis, which is the chance of recovery, varies widely. When all CUP types are looked at together, average survival time is about 9 to 12 months after diagnosis. However, survival rates vary greatly depending on the where the cancer is located, how much it has spread, cancer cell type, treatments, and more.

Often, treatment options are limited for people with CUP, since the cancer has often spread to several parts of the body before it is diagnosed. However, some patients with CUP have a cancer that can be successfully treated. These differences and survival rates are discussed in the Treatment Options section.

It is important to remember that statistics on the survival rates for people with CUP are an estimate. The estimate comes from annual data based on the number of people with CUP in the United States. People should talk with their doctor if they have questions about this information. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society.

The next section in this guide is Risk Factors. It explains what factors may increase the chance of developing this disease. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Risk Factors

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will find out more about the factors that increase the chance of developing this type of cancer. To see other pages, use the menu.

A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

Since CUP can be almost any type of primary cancer, the risk factors for all types of cancer are risk factors for CUP. The following factors may raise a person’s risk of developing CUP:

  • Age. The average age of people diagnosed with CUP is 60.

  • Tobacco use. This includes cigarette smoking, chewing tobacco, and cigar smoking.

  • Sun exposure. Getting too much sun may increase cancer risk. Protect your skin from the sun. 

  • Exposure to large amounts of radiation.

  • Exposure to chemicals in some manufacturing industries.

  • Poor nutrition. Not following a healthy diet may raise the risk of developing cancer.

  • Lack of exercise. Not getting regular physical activity may increase the risk of developing cancer. 

  • Family history. If your family has a history of cancer, then your risk of cancer increases. A family history means more than 1 brother, sister, parent, or grandparent has been diagnosed with breast, ovarian, or colorectal cancer.

The next section in this guide is Symptoms and Signs. It explains what body changes or medical problems this disease can cause. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Symptoms and Signs

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will find out more about body changes and other things that can signal a problem that may need medical care. To see other pages, use the menu.

Because CUP can appear anywhere in the body, the first symptoms can be very different. Usually, symptoms are related to the areas of the body where the cancer is found. Common sites of cancer involvement include the liver, lungs, bones, or lymph nodes. Symptoms or signs may include any of those listed below. Sometimes, people with CUP do not have any of these changes. Or, the cause of a symptom may be another medical condition that is not cancer. 

  • Long-lasting pain in a specific area of the body

  • Loss of appetite

  • Unexplained weight loss

  • A cough or hoarseness that doesn’t go away

  • Thickening or lump in any part of the body

  • Changes in bowel or bladder habits

  • Unusual bleeding or discharge

  • Recurring fever or night sweats

If you are concerned about any changes you experience, please talk with your doctor. Your doctor will ask how long and how often you’ve been experiencing the symptom(s), in addition to other questions. This is to help find out the cause of the problem, called a diagnosis.

If cancer is diagnosed, a person's signs and symptoms often help the doctor plan effective treatment, even when the primary site cannot be found. Relieving symptoms is also an important part of cancer care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

The next section in this guide is Diagnosis. It explains what tests may be needed to learn more about the cause of the symptoms. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Diagnosis

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will find a list of common tests, procedures, and scans that doctors use to find the cause of a medical problem. To see other pages, use the menu.

By its very nature, CUP is found after it has spread to another part of the body from where it started, which is called metastasis. Therefore, doctors use many tests to try to find where in the body the cancer began, called the primary site. Some tests may also determine which treatments may be most effective.

This list describes options for diagnosing CUP and trying to find the primary site. Not all tests listed below will be used for every person. Your doctor may consider these factors when choosing a diagnostic test:

  • The type of cancer suspected

  • Your signs and symptoms

  • Your age and medical condition

  • The results of earlier medical tests


A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only the examination of a biopsy specimen by a pathologist can make a definite diagnosis. A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease. Careful evaluation and testing of the tumor tissue removed during a biopsy can sometimes give clues to where the tumor began.

Evaluation by a pathologist

A pathologist diagnoses cancer by looking at the tumor sample collected during a biopsy. The pathologist can sometimes predict the primary site of the tumor based on the appearance of the tumor cells under a microscope or based on the results of special stains, known as immunohistochemical (IHC) stains, that are part of the standard pathologic evaluation. These results, which are often presented in a pathology report, give important information about the cancer and help doctors plan additional testing.

When predicting the location of the primary site is not possible, an additional test called a molecular cancer classifier assay may be considered. For this test, the pathologist uses tumor tissue collected during the biopsy. This new diagnostic test can accurately predict the site where the tumor began in many patients with CUP, using a technique called gene expression profiling. The results of this new diagnostic test are often useful in helping choose treatment options. Learn more about gene expression profiling in the Treatment Options and Latest Research sections.

Evaluation by an oncologist

Once CUP is diagnosed, an oncologist will do more tests to search for the primary site and find out how far the cancer has spread. This is called a clinical evaluation. An oncologist is a doctor who specializes in treating people with cancer.

For most people with CUP, the primary site is not found, even after extensive evaluation. For this reason, several diagnostic tests may be done to evaluate specific signs and symptoms, including:

  • Medical history. The doctor will ask detailed questions about previous illnesses, surgeries, and medications. Doctors are able to help more if they also know as much information as possible about smoking history, drug use, previous moles or benign (noncancerous) tumors, and any exposure to radiation, asbestos, or other chemicals known to be dangerous. A complete family medical history may also give your doctor important clues, especially if 1 or more siblings, parents, or grandparents have had breast, ovarian, or colorectal cancer.

  • Physical examination. The doctor will do a thorough physical examination of the entire body, including the lymph nodes, pelvis, breasts, rectum, and genitals.

  • Urine and blood tests. These tests can find certain tumor markers and proteins that may help indicate where the cancer began. Tumor markers are substances found at higher-than-normal levels in the blood, urine, or body tissues of some people with cancer. Tumor markers are made either by the tumor or by the body as a result of cancer or other conditions.

    For example, patients who have cancer in the neck lymph nodes and the Epstein-Barr virus (EBV) may have nasopharyngeal cancer. Also, high levels of the proteins human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) may mean a young man with poorly differentiated carcinoma has a germ cell tumor.

  • X-ray. An x-ray is a way to create a picture of the structures inside of the body using a small amount of radiation.

  • Computed tomography (CT or CAT) scan of the chest and abdomen. A CT scan creates a 3-dimensional picture of the inside of the body using x-rays taken from different angles. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. For CUP, a CT scan can show cancer in the abdomen and chest. A CT scan can also be used to measure the tumor’s size. Sometimes, a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein or given as a liquid to swallow.

  • Positron emission tomography (PET) or PET-CT scan. A PET scan is usually combined with a CT scan (see above), called a PET-CT scan. However, you may hear your doctor refer to this procedure just as a PET scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive sugar substance is injected into the patient’s body. This sugar substance is taken up by cells that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body.

    For most patients with CUP, a PET scan is not included in the initial evaluation because it does not improve the ability to locate the primary site when compared to CT scanning alone. However, a PET scan may provide valuable information in specific situations. Patients with CUP who have 1 area of cancer where local treatment, such as surgery or radiation therapy, is being considered should have a PET scan to make sure that no other parts of the body have cancer. For people with squamous cell carcinoma involving lymph nodes in the neck (see the Subtypes section), a PET-CT scan is often useful in identifying a primary site in the head and neck area.

  • Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. MRI can also be used to measure the tumor’s size. A special dye called a contrast medium is given before the scan to create a clearer picture. This dye can be injected into a patient’s vein or given as a liquid to swallow. In some parts of the body, especially the brain and spinal column, MRI provides more information than CT scans. In addition, women with cancer in the axillary lymph nodes, located under the arm, should have a breast MRI, since this test can sometimes find a small breast cancer that cannot be seen on a mammogram (see below).

  • Endoscopy. An endoscopy allows the doctor to see inside the body with a thin, lighted, flexible tube called an endoscope. The person may be sedated as the tube is inserted through the mouth, down the esophagus, and into the stomach and small bowel. Sedation is giving medication to become more relaxed, calm, or sleepy.

    Similar procedures are named according to the part of the body being looked at. For example, a bronchoscopy allows doctors to look inside the bronchial tubes (lungs), and a colonoscopy allows doctors to look inside the colon and rectum.

    Endoscopy is used for patients with CUP to evaluate specific symptoms. For example, patients with squamous cell carcinoma in the neck lymph nodes should always have a complete endoscopy of the nasopharynx, throat, and larynx (voice box) to search for a primary tumor.

  • Prostate-specific antigen (PSA) test. Prostate-specific antigen (PSA) is a substance released by prostate tissue. A PSA test finds higher-than-normal levels of PSA in a man’s blood, which may mean a man has prostate cancer or a noncancerous condition, such as benign prostatic hyperplasia (BPH) or prostatitis (inflammation of the prostate). Men with CUP should have their PSA level measured, since higher-than-normal levels usually identify the prostate as the primary site.

  • Mammography. Women should have a mammogram if they have cancer in the axillary lymph nodes or in other areas that might suggest metastatic breast cancer, such as cancer in the bone, or fluid around the lungs.

After diagnostic tests are done, your doctor will review all of the results with you. These results may help determine the type of tumor and guide the development of your treatment plan.

The next section in this guide is Subtypes. It describes the different CUP tumors that may be diagnosed. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Subtypes

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will find descriptions of the most common types of CUP tumors. To see other pages, use the menu.

Most people with CUP have 1 of these 4 types of tumors:

  • Adenocarcinoma. Nearly 60% of people with CUP have adenocarcinoma. Adenocarcinoma can develop in the glandular tissue of most internal organs, including the lungs, stomach, pancreas, colon, ovary, and breast. Because of this, it is extremely difficult for a pathologist to tell where an adenocarcinoma began when it is found at a metastatic site.

    Additional diagnostic tests on biopsy samples, called IHC stains, can predict the primary site about 30% to 40% of the time. A molecular cancer classifier assay of the biopsy specimen can accurately predict the primary site for most other patients. Learn more about gene expression profiling in the Treatment Options and Latest Research sections.

  • Poorly differentiated carcinoma. About 20% to 30% of people with CUP have poorly differentiated carcinomas. Pathologists do extra testing on biopsy samples of these tumors because some very treatable cancers may be first diagnosed as poorly differentiated carcinoma. Similar to patients with adenocarcinoma, a molecular cancer classifier assay can usually predict the tumor type of the primary site and is useful in helping choose treatment options. If this testing shows the cancer is lymphoma, germ cell carcinoma, or neuroendocrine carcinoma, effective treatments are often available.

  • Squamous cell carcinoma. About 5% to 10% of people with CUP have squamous cell carcinoma. If squamous cell carcinoma is found in the cervical lymph nodes in the neck, the primary site is often in the head and neck area. If it is found in the inguinal lymph nodes in the groin, the primary site may be in the vulva, vagina, cervix, anus, or bladder. A careful search is important because these cancers can often be successfully treated.

  • Neuroendocrine carcinoma. About 1% to 5% of people with CUP have neuroendocrine carcinoma. These cancers are more often found with IHC stains. Some of these tumors are aggressive and fast growing, but combination chemotherapy (see the Treatment Options section) may be effective. Others are very slow growing, and people sometimes live for several years, even without treatment.

Information about the tumor’s subtype will help the doctor recommend a specific treatment plan. The next section in this guide is Treatment Options. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Treatment Options

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will learn about the different ways doctors may treat this type of cancer. To see other pages, use the menu.

This section tells you the treatments that are the standard of care for CUP. “Standard of care” means the best treatments known. When making treatment plan decisions, patients are also encouraged to consider clinical trials as an option. A clinical trial is a research study that tests a new approach to treatment. Doctors want to learn if it is safe, effective, and possibly better than the standard treatment. Clinical trials can test a new drug, a new combination of standard treatments, or new doses of standard drugs or other treatments. Your doctor can help you consider all your treatment options. To learn more about clinical trials, see the About Clinical Trials and Latest Research sections.

Planning treatment

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Cancer care teams also include a variety of other health care professionals, including physician assistants, oncology nurses, social workers, pharmacists, counselors, dietitians, and others.

To figure out the best treatment plan for CUP, doctors rely on the answers to the following questions:

  • Was the primary site found during clinical and imaging testing? If so, treatment should follow guidelines for an advanced (metastatic) tumor of that primary tumor type. 

  • Did the pathologist identify a primary tumor or a specific tumor type, such as lymphoma or germ cell tumor? If so, treatment should follow guidelines for the specific tumor type.

  • If no primary site was found, does this CUP fit into any of the subgroups for which specific treatment is recommended? Subgroups are listed below.

  • If no primary site was found and this CUP does not fit into any of the specific subgroups, will disease-directed treatment be helpful? If so, should treatment be based on the tumor type predicted by the molecular cancer classifier assay, or should it be treated with an empiric (general) chemotherapy program (see below)? The chance that chemotherapy will be effective depends on the location of the tumor, the number of metastases involved, and the person's overall health.

Treatment overview

The common types of cancer treatment are described below. This section is followed by an outline of treatment for each of the recognized CUP subgroups. Finally, treatment options are outlined for CUP patients whose clinical features do not fit into any of the recognized subgroups.

Because CUP has usually spread to at least 1 place when diagnosed, this type of tumor can rarely be removed by surgery or treated with localized radiation therapy. Therefore, chemotherapy is the most common treatment for CUP. Chemotherapy may be able to completely get rid of some tumors.

Your care plan may also include treatment for symptoms and side effects, which is an important part of cancer care. Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Also, talk about the goals of each treatment with your doctor and what you can expect while receiving the treatment. Learn more about making treatment decisions.

For many patients, a diagnosis of CUP can be very stressful and, at times, difficult to bear. Patients and their families are encouraged to talk about the way they are feeling with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, including through a support group.


Chemotherapy is the use of drugs to destroy cancer cells, usually by stopping the cancer cells’ ability to grow and divide. Chemotherapy is given by a medical oncologist, a doctor who specializes in treating cancer with medication.

Systemic chemotherapy gets into the bloodstream to reach cancer cells throughout the body. Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally).

A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive 1 drug at a time or combinations of different drugs at the same time. The medications used to treat cancer are continually being studied.

The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhea. These side effects usually go away once treatment has finished.

Learn more about the basics of chemotherapy and preparing for treatment. 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 by using searchable drug databases.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen (schedule) usually consists of a specific number of treatments given over a set period of time.

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. Learn more about the basics of radiation therapy.


Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. A surgical oncologist is a doctor who specializes in treating cancer using surgery. The extent and location of the surgery depends on where the cancer is found and its size. Learn more about the basics of cancer surgery.

Targeted therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to healthy cells.

A number of targeted cancer therapies are approved by the U.S. Food and Drug Administration (FDA) to treat specific types of cancer. Although none of these drugs is currently approved to treat CUP, being able to accurately predict where a CUP started may also help identify a targeted drug that could be beneficial. For example, if a CUP is thought to have started in the lung, it may respond to a targeted therapy currently approved for lung cancer.

Talk with your doctor about possible side effects for a specific medication and how they can be managed. Learn more about the basics of targeted treatments.

Hormone therapy

The goal of hormone therapy is to alter the activity of hormones in the body, usually by trying to lower their levels or block their actions. Hormone therapy may be given to help stop a tumor from growing or to relieve symptoms caused by the tumor. This type of treatment may be an option for people in specific CUP subgroups (see below).

Treatment options for specific CUP subgroups

One of the following subgroups may be identified during the initial clinical and pathologic evaluation. They each have specific treatment options that are often recommended.

  • Women with adenocarcinoma located only in the axillary lymph nodes. Treatment usually follows the guidelines for stage II breast cancer, even if no primary site in the breast can be found. Local treatment includes surgical removal of the breast (mastectomy) or surgical removal of the lymph nodes (axillary node dissection) plus radiation therapy to the breast. After surgery, chemotherapy, hormone therapy, or both may be recommended, depending on the number of lymph nodes with cancer and estrogen/progesterone receptor (ER/PR) status, HER2 status, and other features of the tumor.

  • Women with peritoneal carcinomatosis, which is adenocarcinoma on the surface of the abdominal cavity. Treatment usually follows the guidelines for stage III ovarian cancer, even for women with healthy ovaries or whose ovaries have been removed. Whenever possible, surgery to remove as much of the cancer as possible, known as debulking surgery, should be performed. Chemotherapy with a taxane/platinum combination, which is used in the treatment of ovarian cancer, is recommended after surgery. CA-125 is often a useful tumor marker for monitoring how well treatment is working. About 20% to 25% of women live for a long time after receiving treatment.

  • Young men with poorly differentiated carcinoma found in the mediastinum (center of the chest between the lungs) or retroperitoneum (back of the abdominal cavity). Some men in this group may have a germ cell tumor, even if the diagnosis cannot be made by the pathologist. High levels of HCG and AFP in the blood strongly suggest a germ cell tumor. Men with this subtype usually receive chemotherapy according to the guidelines for the treatment of later-stage testicular cancer. After chemotherapy, surgery to remove any remaining cancer is often needed. About 30% of men in this group have the cancer successfully treated.

  • Squamous cell carcinoma in the cervical (neck) lymph nodes. Even if a primary site in the head and neck is not found after a careful search, people with tumors in this subgroup generally receive treatment according to the guidelines for locally advanced head and neck cancer. This usually includes radiation therapy and chemotherapy given at the same time. For some patients with small cervical lymph nodes with cancer, treatment with radiation therapy alone or surgery followed by radiation therapy is enough. About 40% to 60% of people with this diagnosis live a long time after treatment.

  • Squamous cell carcinoma in the inguinal (groin) lymph nodes. Treatment generally includes surgical removal of all inguinal lymph nodes or radiation therapy. The doctor may recommend combining chemotherapy with radiation therapy.

  • Patients who have only a single metastasis. This group includes a broad range of patients, since the single metastasis may be found in any part of the body, such as the lymph nodes, brain, lung, or liver. Depending on the location, treatment usually includes either surgical removal of the tumor or radiation therapy. Most people eventually develop metastases in other parts of the body, but this sometimes occurs after a long time without any disease.

  • Men with metastases only in the bones and/or an elevated PSA level. Treatment for this subtype usually follows the guidelines for the treatment of advanced prostate cancer. Hormone therapy, also called androgen deprivation, often causes long remissions. A remission is the disappearance of the signs and symptoms of CUP.

  • Patients with adenocarcinoma in the liver and/or abdomen. For tumors that have only spread in the abdomen, special pathology tests (IHC stains or molecular tumor profiling) sometimes suggest that the cancer started in the colon. These tumors are usually treated according to the guidelines for later-stage colon cancer, even if a primary site cannot be located with a colonoscopy.

  • Patients with poorly differentiated neuroendocrine tumors. Although the primary site is usually not found, these types of neuroendocrine tumors often respond to chemotherapy with platinum/etoposide (Etopophos), with or without taxane (docetaxel [Taxotere] or paclitaxel [Taxol]). This treatment can effectively shrink the cancer and improve cancer-related symptoms about 60% of the time. About 10% to 15% of people experience a complete remission with chemotherapy, and some live for a long time after treatment.

  • Patients with well-differentiated neuroendocrine tumors. Most well-differentiated neuroendocrine tumors, such as carcinoid tumors or islet cell tumors, begin in the intestinal tract or pancreas. For cancers with an unknown primary site, the metastases are usually found in the liver. It is usually easy for the pathologist to tell the difference between well-differentiated and poorly differentiated neuroendocrine tumors. This distinction is important because the chemotherapy recommended for poorly differentiated neuroendocrine tumors is usually not effective for well-differentiated tumors. Well-differentiated neuroendocrine tumors usually grow slowly, and patients often live for several years, even without treatment. In general, the treatment follows the guidelines for advanced carcinoid tumors.

All patients with CUP are encouraged to talk with their doctor about participating in a clinical trial that is evaluating a new approach to treatment. In addition, talk with your doctor about the possible side effects and goals of each treatment option.

Treatment for those not in a specific CUP subgroup

About 75% of all people with CUP do not have the characteristics of any of the specific subgroups described above. Most of the patients in this group have adenocarcinoma or poorly differentiated carcinoma (see Subtypes). The success of treatment for this group varies widely. Many of these patients have cancers that are resistant to treatment. However, others experience significant benefits from treatment.

The recommendations for treating these patients are in the process of changing based on ongoing scientific research. Until recently, standard treatment typically included a generalized chemotherapy approach called empiric chemotherapy. Empiric chemotherapy uses a combination of drugs traditionally known to work against a variety of cancers. In the past, many types of advanced cancers were treated in similar ways, and so this type of approach offered the best chance of success in many cases. Only about 5% of patients are cured with empiric chemotherapy, but it can shrink tumors in 35% to 40% of patients. Around 20% to 25% of patients who receive this treatment live for at least 2 years after diagnosis.

During the last 15 years, important improvements have been made in the treatment of many types of cancer. Many of the drugs responsible for these improvements are called targeted therapies (see above). Unlike traditional chemotherapy, targeted drugs work best for specific types of cancer with specific tumor features. For example, a drug that targets a tumor abnormality found in lung cancer may not work at all for colon cancer, and vice versa. Therefore, it is increasingly difficult to design an empiric/generalized treatment program for patients with CUP that provides the best results for different cancer types.

At the same time, new diagnostic tests are available that can predict the primary site for people with CUP, even when the primary site cannot be found using scans and other clinical evaluations. Pathologists perform these new tests, called molecular cancer classifier assays, on tumor tissue taken during a biopsy. More and more scientific evidence shows that in most cases the predictions from these assays are accurate.

Although scientific evidence is not complete, it now appears that treatment directed toward the specific tumor type predicted by gene expression profiling offers advantages over empiric chemotherapy. For example, a patient predicted to have a primary site in the colon would benefit more from a treatment plan designed for later-stage colon cancer than from empiric chemotherapy. Such a treatment plan would include targeted therapies developed specifically for colon cancer. Currently, all of the information from clinical trials consistently shows better treatment outcomes with treatment guided by gene expression profiling than with empiric chemotherapy.

Getting care for symptoms and side effects

Cancer and its treatment often cause side effects. In addition to treatment to slow, stop, or eliminate the cancer, an important part of cancer care is relieving a person’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Palliative care is any treatment that focuses on reducing symptoms, improving quality of life, and supporting patients and their families. Any person, regardless of age or type and stage of cancer, may receive palliative care. It works best when palliative care is started as early as needed in the cancer treatment process.

People often receive treatment for the cancer and treatment to ease side effects at the same time. Even for patients whose tumors do not respond to chemotherapy, treatments are available to reduce symptoms. In fact, patients who receive both often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional support, and other therapies. You may also receive palliative treatments similar to those meant to eliminate the cancer, such as chemotherapy, surgery, or radiation therapy. Talk with your doctor about the goals of each treatment in your treatment plan.

Before treatment begins, talk with your health care team about the possible side effects of your specific treatment plan and palliative care options. And during and after treatment, be sure to tell your doctor or another health care team member if you are experiencing a problem so it can be addressed as quickly as possible. Learn more about palliative care.

Remission and the chance of recurrence

A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having “no evidence of disease” or NED. For patients who receive chemotherapy and experience remission, treatment is usually stopped after 4 to 6 months.

A remission may be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. While many remissions are permanent, it’s important to talk with your doctor about the possibility of the cancer returning. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.

If the cancer does return after chemotherapy or other treatment, it is called recurrent cancer. It may come back in the same place or in other areas of the body. When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence. After testing is done, you and your doctor will talk about your treatment options.

Chemotherapy will usually be recommended, either with the same drugs you received before or with a new combination. If your first treatment was based on the tumor type predicted by gene expression profiling, second-line treatment will likely continue to follow the standard treatment for that tumor type. Your doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent cancer. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

People with recurrent cancer often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope. Learn more about dealing with cancer recurrence.

If treatment fails

Recovery from cancer is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.

This diagnosis is stressful, and advanced cancer is difficult to discuss for many people. However, it is important to have open and honest conversations with your doctor and health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Making sure a person is physically comfortable and free from pain is extremely important.

Patients who have advanced cancer and who are expected to live less than 6 months may want to consider a type of palliative care called hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to think about where you would be most comfortable: at home, in the hospital, or in a hospice environment. Nursing care and special equipment can make staying at home a workable alternative for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

The next section in this guide is About Clinical Trials. It offers more information about research studies that are focused on finding better ways to care for people with cancer. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - About Clinical Trials

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will learn more about clinical trials, which are the main way that new medical approaches are tested to see how well they work. To see other pages, use the menu.

What are clinical trials?

Doctors and scientists are always looking for better ways to care for patients with CUP. To make scientific advances, doctors create research studies involving volunteers, called clinical trials. In fact, every drug that is now approved by the FDA was tested in clinical trials.

Many clinical trials focus on new treatments. Researchers want to learn if a new treatment is safe, effective, and possibly better than the treatment doctors use now. For patients with CUP, most clinical trials evaluate new drugs or different combinations of existing drugs. In addition, new diagnostic tests are currently being studied to identify the primary site, which can help determine more specific treatment options. Patients who participate in clinical trials can be some of the first to get a treatment before it is available to the public. However, there is no guarantee that the new treatment will be safe, effective, or better than what doctors use now.

Some clinical trials study new ways to relieve symptoms and side effects during treatment. Others study ways to manage the late effects that may happen a long time after treatment. Talk with your doctor about clinical trials for symptoms and side effects. There are also clinical trials studying ways to prevent cancer.

Deciding to join a clinical trial

People decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that these studies are the only way to make progress in treating cancer. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with cancer.

Sometimes people have concerns that, in a clinical trial, they may receive no treatment by being given a placebo or a “sugar pill.” However, placebos are usually combined with standard treatment in most cancer clinical trials. When a placebo is used in a study, it is done with the full knowledge of the participants. Find out more about placebos in cancer clinical trials.

Patient safety and informed consent

To join a clinical trial, patients must participate in a process known as informed consent. During informed consent, the doctor should list all of the patient’s options so that the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment.

Patients who participate in a clinical trial may stop participating at any time for any personal or medical reason. This may include that the new treatment is not working or there are serious side effects. Clinical trials are also closely monitored by experts who watch for any problems with each study. It is important that patients participating in a clinical trial talk with their doctor and researchers about who will be providing their treatment and care during the clinical trial, after the clinical trial ends, and/or if the patient chooses to leave the clinical trial before it ends.

Finding a clinical trial

Research through clinical trials is ongoing for all types of cancer. For specific topics being studied for CUP, learn more in the Latest Research section.

Cancer.Net offers a lot of information about cancer clinical trials in other areas of the website, including a complete section on clinical trials and places to search for clinical trials for a specific type of cancer.

PRE-ACT, Preparatory Education About Clinical Trials

In addition, this website offers free access to a video-based educational program about cancer clinical trials, located outside of this guide.

The next section in this guide is Latest Research. It explains areas of scientific research currently going on for this type of cancer. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Latest Research

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will read about the scientific research being done now to learn more about this type of cancer and how to treat it. To see other pages, use the menu.

Doctors are working to learn more about CUP, ways to prevent cancer, how to best treat CUP, and how to provide the best care to people diagnosed with this disease. The following areas of research may include new options for patients through clinical trials. Always talk with your doctor about the diagnostic and treatment options best for you.

  • Using tumor genetics to diagnose the primary site. Different tissues within the body make different proteins, depending on which genes are active. This is called gene expression. For example, some of the genes expressed by healthy lung cells are different from those expressed by healthy colon cells. When cancer develops in these organs, it usually has the same organ-specific pattern of gene expression. It is now possible to analyze a tumor sample from a biopsy to figure out which genes are being expressed. This usually can predict the location where the cancer began.

    As mentioned in the Treatment Options section, site-specific treatment based on gene expression profiling prediction is replacing empiric chemotherapy as the standard treatment for patients with CUP who do not fit into any of the specific subgroups. Ongoing clinical trials continue to look at the outcomes of assay-directed treatment in order to better define its role in treating CUP.

  • Targeted therapy. As outlined in the Treatment Options section, targeted therapy is directed at specific molecular abnormalities within the cancer cell or the surrounding tissue environment that contributes to cancer growth and spread. These abnormalities include gene mutations in the tumor and abnormal activity of various signaling proteins within cancer cells. Learn more about the basics of targeted treatments.

    Several targeted therapies are approved by the FDA for specific cancers, either used alone or with chemotherapy. Examples of these targeted treatments include HER2 targeted therapy for HER2-positive breast cancer, BRAF inhibitors for BRAF-mutated melanoma, and EGFR inhibitors for EGFR-mutated non-small cell lung cancer. However, no targeted therapies are currently approved to treat CUP specifically, and the targeted drugs approved for other cancers have not been tested for CUP.

    Since CUP actually covers many tumor types, it is likely that some patients would benefit from the targeted therapies already proven to treat specific tumor types. For example, therapies targeting HER2, which is a molecular abnormality found in about 1 of every 5 breast cancers, have dramatically improved treatment results for these patients.

    Could a patient with CUP who is predicted to have breast cancer by gene expression profiling have an abnormality in HER2? If so, would treatment with a therapy targeting HER2 benefit this patient? The answer to both questions is likely to be “yes,” but no clinical trials have addressed this issue for HER2 or any other molecular abnormalities. In fact, tumors from patients with CUP are not routinely tested for HER2 abnormalities or for any of the other molecular abnormalities for which targeted treatments exist.

    A recent study found that the incidence of potentially treatable molecular abnormalities (using targeted treatments already approved for other cancers) is approximately 25% in CUP. In ongoing clinical trials, people with CUP whose tumors have specific molecular abnormalities are being treated with drugs targeted against the abnormality. It is likely that these clinical trials will identify additional effective treatment options for specific patient groups.

  • New types of treatment. Patients with CUP that no longer responds to standard treatment may want to consider clinical trials that test new types of treatment.  Of particular interest are drugs that induce the immune system to fight cancer, such as anti-PD-1 and anti-PD-L1 agents, because these drugs have already been proven effective against a variety of cancer types. In addition, many new drugs are being tested for the first time in studies called phase I clinical trials. The goals of these studies are to identify the side effects and best doses for these new drugs, as well as to learn if they are effective against cancer.

  • Palliative care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current cancer treatments to improve patients’ comfort and quality of life.

Looking for More About the Latest Research?

If you would like additional information about the latest areas of research regarding CUP, explore these related items that take you outside of this guide:

The next section in this guide is Coping with Treatment. It offers some guidance in how to cope with the physical, emotional, and social changes that cancer and its treatment can bring. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Coping with Treatment

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will learn more about coping with the physical, emotional, social, and financial effects of cancer and its treatment. This page includes several links outside of this guide to other sections of this website. To see other pages, use the menu.

Every cancer treatment can cause side effects or changes to your body and how you feel. For many reasons, people don’t experience the same side effects even when given the same treatment for the same type of cancer. This can make it hard to predict how you will feel during treatment.

As you prepare to start cancer treatment, it is normal to fear treatment-related side effects. It may help to know that your health care team will work to prevent and relieve side effects. Doctors call this part of cancer treatment “palliative care.” It is an important part of your treatment plan, regardless of your age or the subtype of your disease.

Coping with physical side effects

Common physical side effects from each treatment option for CUP are described in the Treatment Options section. Learn more about side effects of cancer and its treatment, along with ways to prevent or control them. Changes to your physical health depend on several factors, including the cancer’s subtype, the length and dose of treatment, and your general health.


Sometimes, physical side effects can last after treatment ends. Doctors call these long-term side effects. They call side effects that occur months or years after treatment late effects. Treating long-term side effects and late effects is an important part of survivorship care. Learn more by reading the Follow-up Care section of this guide or talking with your doctor.

Coping with emotional and social effects

You can have emotional and social effects as well as physical effects after a cancer diagnosis. This may include dealing with difficult emotions, such as anxiety or anger, or managing your stress level. Sometimes, patients have problems expressing how they feel to their loved ones, or people don’t know what to say in return.

Patients and their families are encouraged to share their feelings with a member of their health care team. You can also find coping strategies for emotional and social effects in a separate section of this website. This section includes many resources for finding support and information to meet your needs.

Coping with financial effects

Cancer treatment can be expensive. It is often a big source of stress and anxiety for people with cancer and their families. In addition to treatment costs, many people find they have extra, unplanned expenses related to their care. For some people, the high cost stops them from following or completing their cancer treatment plan. This can put their health at risk and may lead to higher costs in the future. Learn more about managing financial considerations, in a separate part of this website.

Caring for a loved one with cancer

Family members and friends often play an important role in taking care of a person with CUP. This is called being a caregiver. Caregivers can provide physical, practical, and emotional support to the patient, even if they live far away.

Caregivers may have a range of responsibilities on a daily or as-needed basis. Below are some of the responsibilities caregivers take care of:

  • Providing support and encouragement

  • Giving medications

  • Helping manage symptoms and side effects

  • Coordinating medical appointments

  • Providing a ride to appointments

  • Assisting with meals

  • Helping with household chores

  • Handling insurance and billing issues

Learn more about caregiving.

Talking with your health care team about side effects

Before starting treatment, talk with your doctor about possible side effects. Ask:

  • Which side effects are most likely?

  • When are they are likely to happen?

  • What can we do to prevent or relieve them?

Be sure to tell your health care team about any side effects that happen during treatment and afterward, too. Tell them even if you don’t think the side effects are serious. This discussion should include physical, emotional, and social effects of cancer.

Also, ask how much care you may need at home and with daily tasks during and after treatment. This can help you make a caregiving plan.

The next section in this guide is Follow-up Care. It explains the importance of checkups after cancer treatment is finished. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Follow-Up Care

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will read about your medical care after cancer treatment is finished and why this follow-up care is important. To see other pages, use the menu.

Care for people diagnosed with cancer doesn’t end when active treatment has finished. Your health care team will continue to check to make sure the cancer has not returned, manage any side effects, and monitor your overall health. This is called follow-up care.

Your follow-up care may include regular physical examinations, medical tests, or both. Doctors want to keep track of your recovery in the months and years ahead. Patients with CUP are a diverse group of people and recommended treatment plans vary, so the possible short-term and long-term effects of treatment are different. In addition, recommended follow-up and long-term prognosis varies from person to person. The recommendations in this section are directed primarily at patients who are in remission after successful treatment.

In general, close follow-up care is recommended during the first year after treatment for CUP ends, with physical examinations and routine laboratory tests every 2 months and appropriate x-rays and scans every 3 to 4 months. After the first year, follow-up care will continue based on a personalized schedule.

Learn more about the importance of follow-up care.

Watching for recurrence

One goal of follow-up care is to check for a recurrence. Cancer recurs because small areas of cancer cells may remain undetected in the body. Over time, these cells may increase in number until they show up on test results or cause signs or symptoms.

During follow-up care, a doctor familiar with your medical history can give you personalized information about your risk of recurrence. Your doctor will also ask specific questions about your health. Some people may have blood tests or imaging tests done as part of regular follow-up care, but testing recommendations depend on several factors, including the subgroup or subtype of CUP originally diagnosed and the types of treatment given.

People who were treated for CUP should tell their doctor about any new symptoms right away. Talk with your doctor during your follow-up care appointments about specific symptoms to watch for.

Managing long-term and late side effects

Most people expect to experience side effects when receiving treatment. However, it is often surprising to survivors that some side effects may linger beyond the treatment period. These are called long-term side effects. In addition, other side effects called late effects may develop months or even years afterwards. Long-term and late effects can include both physical and emotional changes.

For patients in specific, treatable subgroups (see the Treatment Options section) who received treatment based on guidelines for various cancers of a known primary site, the side effects and post-treatment recommendations are similar to those of that specific cancer. Please refer to that specific cancer type section for more information. If you had a treatment known to cause specific late effects, you may have certain physical examinations, scans, or blood tests to help diagnose and manage them. 

For people who receive chemotherapy, most of the treatment-related side effects, such as low blood counts, fatigue, weakness, and joint aches, go away within 4 to 6 weeks after treatment ends. However, other possible side effects like peripheral neuropathy, which is numbness, tingling, or pain in the hands and feet, improve slowly and may take 6 to 12 months to go away.

Talk with your doctor about your risk of developing such side effects based on the subtype of CUP, your individual treatment plan, and your overall health.

Keeping personal health records

You and your doctor should work together to develop a personalized follow-up care plan. Be sure to ask about any concerns you have about your future physical or emotional health. ASCO offers forms to help create a treatment summary to keep track of the cancer treatment you received and develop a survivorship care plan once treatment is completed.

This is also a good time to decide who will lead your follow-up care. Some survivors continue to see their oncologist, while others transition back to the general care of their family doctor or another health care professional. This decision depends on several factors, including the type and stage of cancer, side effects, health insurance rules, and your personal preferences.

If a doctor who was not directly involved in your cancer care will lead your follow-up care, be sure to share your cancer treatment summary and survivorship care plan forms with him or her, as well as all future health care providers. Details about your cancer treatment are very valuable to the health care professionals who will care for you throughout your lifetime.

The next section in this guide is Survivorship. It describes how to cope with challenges in everyday life after a cancer diagnosis. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Survivorship

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will read about how to cope with challenges in everyday life after a cancer diagnosis. To see other pages, use the menu.

What is survivorship?

The word “survivorship” means different things to different people. Common definitions include:

  • Having no signs of cancer after finishing treatment.

  • Living with, through, and beyond cancer. According to this definition, cancer survivorship begins at diagnosis and includes people who continue to have treatment over the long term, to either reduce the risk of recurrence or to manage chronic disease.

Survivorship is one of the most complicated parts of having cancer. This is because it is different for everyone.

Survivors may experience a mixture of strong feelings, including joy, concern, relief, guilt, and fear. Some people say they appreciate life more after a cancer diagnosis and have gained a greater acceptance of themselves. Others become very anxious about their health and uncertain of how to cope with everyday life.

Survivors may feel some stress when frequent visits to the health care team end following treatment. Often, relationships built with the cancer care team provide a sense of security during treatment, and people miss this source of support. This may be especially true as new worries and challenges surface over time, such as any late effects of treatment, emotional challenges including fear of recurrence, sexuality and fertility concerns, and financial and workplace issues.

Every survivor has individual concerns and challenges. With any challenge, a good first step is being able to recognize your fears and talk about them. Effective coping requires:

  • Understanding the challenge you are facing

  • Thinking through solutions

  • Asking for and allowing the support of others

  • Feeling comfortable with the course of action you choose

Many survivors find it helpful to join an in-person support group or an online community of survivors. This allows you to talk with people who have had similar first-hand experiences. Other options for finding support include talking with a friend or member of your health care team, individual counseling, or asking for assistance at the learning resource center of the center where you received treatment.

Changing role of caregivers

Family members and friends may also go through periods of transition. A caregiver plays a very important role in supporting a person diagnosed with cancer, providing physical, emotional, and practical care on a daily or as-needed basis. Many caregivers become focused on providing this support, especially if the treatment period lasts for many months or longer.

However, as treatment is completed, the caregiver's role often changes. Eventually, the need for caregiving related to the cancer diagnosis will become much less or come to an end. Caregivers can learn more about adjusting to life after caregiving in this article.

A new perspective on your health

For many people, survivorship serves as a strong motivator to make positive lifestyle changes.

People recovering from CUP are encouraged to follow established guidelines for good health, such as not smoking, limiting alcohol, eating well, and managing stress. Regular physical activity can help rebuild your strength and energy level. Your health care team can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about making healthy lifestyle choices.

In addition, it is important to have recommended medical checkups and tests (see Follow-up Care) to take care of your health. Cancer rehabilitation may also be recommended, and this could mean any of a wide range of services such as physical therapy, career counseling, pain management, nutritional planning, and/or emotional counseling. The goal of rehabilitation is to help people regain control over many aspects of their lives and remain as independent and productive as possible.

Talk with your doctor to develop a survivorship care plan that is best for your needs.

Looking for More Survivorship Resources?

For more information about cancer survivorship, explore these related items. Please note that these links will take you to other sections of Cancer.Net:

  • ASCO Answers Cancer Survivorship Guide: Get this 44-page booklet that helps people transition into life after treatment. It includes blank treatment summary and survivorship care plan forms. The booklet is available as a PDF, so it is easy to print out.

  • Cancer.Net Patient Education Video: View a short video led by an ASCO expert that provides information about what comes next after finishing treatment.

  • Survivorship Resources: Cancer.Net offers an entire area of this website with resources to help survivors, including for survivors in different age groups.

The next section offers Questions to Ask the Doctor to help start conversations with your cancer care team. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Questions to Ask the Doctor

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will find some questions to ask your doctor or another member of your health care team to help you better understand your diagnosis, treatment plan, and overall care. To see other pages, use the menu.

Talking often with the doctor is important to make informed decisions about your health care. These suggested questions are a starting point to help you learn more about your cancer care and treatment. You are also encouraged to ask additional questions that are important to you. You may want to print this list and bring it to your next appointment, or download Cancer.Net’s free mobile app for an e-list and other interactive tools to manage your care.

Questions to ask after the initial evaluation

  • Where exactly is the tumor?

  • How large is the tumor?

  • What are the results of the biopsy?

  • Can you explain my pathology report (laboratory test results) to me?

  • Have specialized tests been done by the pathologist to help find the primary site?

  • Would a molecular cancer classifier assay of my biopsy sample help predict a primary site?

  • Will I need to have another biopsy to provide the pathologist with the best possible specimen for examination?

  • What tests or scans are available to help identify a primary site?

  • Should I get a second opinion?

Questions to ask about choosing a treatment and managing side effects

  • Have specialized, pathologic studies of my tumor predicted where my cancer started? If so, will my treatment follow the guidelines for the predicted cancer type?

  • Can my tumor be treated with targeted therapy?

  • What are my treatment options?

  • What clinical trials are available for me? Where are they located, and how do I find out more about them?

  • What treatment plan do you recommend? Why?

  • What is the goal of each treatment? Is it to eliminate the cancer, help me feel better, or both?

  • What is my prognosis?

  • Who will be part of my health care team, and what does each member do?

  • Who will be leading my overall treatment?

  • What are the possible side effects of each treatment, both in the short term and the long term?

  • How will this treatment affect my daily life? Will I be able to work, exercise, or perform my usual activities?

  • Could this treatment affect my sex life? If so, how and for how long?

  • Could this treatment affect my ability to become pregnant or have children? If so, should I talk with a fertility specialist before cancer treatment begins?

  • If I’m worried about managing the costs of cancer care, who can help me?

  • What support services are available to me? To my family?

  • Whom should I call with questions or problems?

  • Is there anything else I should be asking?

Questions to ask about specific treatments

  • What type of treatment is recommended?

  • What is the goal of this treatment?

  • How long will it take to give this treatment?

  • What side effects can I expect during treatment?

  • What are the possible long-term effects of having this treatment?

  • What can be done to prevent or manage the side effects?

Questions to ask about planning follow-up care

  • What is the chance that the cancer will come back? Should I watch for specific signs or symptoms?

  • What long-term side effects or late effects are possible based on the treatment I received?

  • What follow-up tests will I need, and how often will I need them?

  • How do I get a treatment summary and survivorship care plan to keep in my personal records? 

  • Who will be leading my follow-up care?

  • What survivorship support services are available to me? To my family?

The next section in this guide is Additional Resources. It offers some more resources on this website beyond this guide that may be helpful to you. Or, use the menu to choose another section to continue reading this guide.

Unknown Primary - Additional Resources

This section has been reviewed and approved by the Cancer.Net Editorial Board, 08/2016

ON THIS PAGE: You will find some helpful links to other areas of Cancer.Net that provide information about cancer care and treatment. This is the final page of Cancer.Net’s Guide to Cancer of Unknown Primary. To go back and review other pages, use the menu.

Cancer.Net includes many other sections about the medical and emotional aspects of cancer, both for the person diagnosed and their family members and friends. This website is meant to be a resource for you and your loved ones from the time of diagnosis, through treatment, and beyond.

Beyond this guide, here are a few links to help you explore other parts of Cancer.Net:

This is the end of Cancer.Net’s Guide to Cancer of Unknown Primary. Use the menu to select another section to continue reading this guide.