Deprecated: mysql_connect(): The mysql extension is deprecated and will be removed in the future: use mysqli or PDO instead in /home/cancer/public_html/connection.php on line 2

This Website is for Pateints only. We do not deal with Medical Institutions or Pharmaceutical Companies

Cancer Medicine :: Unknown Primary

Cancer of Unknown Primary

How is a cancer of unknown primary treated?

After your cancer is diagnosed, your cancer care team will discuss your treatment options with you. Choosing a treatment plan is an important decision, so it’s important to take time and think about all of the choices.

In creating your treatment plan, the most important factors to consider are the type of cancer and its location. Your cancer care team will also take into account your general state of health and your personal preferences.

Treatment for cancer of unknown primary (CUP) may include:


Surgery for cancer of unknown primary

Surgery is a common treatment for many types of cancer if they are found at an early stage. But because cancer of unknown primary (CUP) has already spread beyond the site where it started, surgery is less likely to be helpful.

Surgery may be an option if the cancer is found only in the lymph nodes or in one organ, where the surgeon may be able to remove it all. However, there’s still a chance that the cancer may be elsewhere in the body. If you are considering surgery as a treatment option, it’s important to understand how likely it is to help you.

The type and extent of surgery will depend on where the cancer is and how extensive it is. If surgery is used, it may be followed by radiation therapy and possibly chemotherapy to try to kill any remaining cancer cells in the body.

Radiation therapy for cancer of unknown primary

Radiation therapy uses high-energy rays or particles to destroy cancer cells or slow their rate of growth. The goal of radiation therapy may change based on the situation.

For some cancers that have not spread too far from where they started, it can be used alone or with other treatments such as surgery with the goal of trying to cure the cancer.

If cancer has spread extensively, radiation can be used to relieve symptoms such as pain, bleeding, trouble swallowing, intestinal blockage, compression of blood vessels or nerves by tumors, and problems caused by metastases to bones.

External beam radiation therapy

The most common way to deliver radiation to a cancer is to carefully focus a beam of radiation from a machine outside the body. This is known as external beam radiation. To reduce the risk of side effects, doctors carefully figure out the exact dose and aim the beam as accurately as they can to hit the target.

External beam radiation therapy is much like getting a diagnostic x-ray, but the radiation is more intense. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time – getting you into place for treatment – usually takes longer. The radiation is usually divided into many treatments over several days or weeks.

Internal radiation therapy (brachytherapy)

Another method of delivering radiation is called internal radiation, interstitial radiation, or brachytherapy. Instead of using radiation beams aimed from a large machine, a radioactive material is placed directly into, or as close as possible to, the cancer. This type of radiation travels a very short distance in the body. The material itself may be left in the body for only a short time, or it may be left there permanently.

Internal radiation therapy lets your doctor give a dose of radiation to a smaller area and in a shorter time than is possible with external radiation treatment.

Sometimes, both internal and external beam radiation therapies are used together.

Possible side effects of radiation therapy

Side effects can vary from patient to patient and depend on the radiation dose and the part of your body treated. Some of the possible side effects are listed below:

General side effects

Fatigue (feeling tired)

Loss of appetite

Low blood counts

Skin changes (like a sunburn at the area where the radiation beams enter the body)

Hair loss (at the site where the beams enter the body)

Side effects from radiation to the head and neck

Radiation therapy to the head and neck area often causes damage to the throat and salivary glands, which can result in:

Throat pain

Mouth sores

Trouble swallowing

Loss of taste


Dry mouth

Over the long term it can also lead to cavities in the teeth and thyroid problems (from damage to the thyroid gland). This might mean that you need pills to replace thyroid hormone.

Side effects from radiation to the chest

Trouble and pain swallowing from irritation of the esophagus (the tube that connects the throat to the esophagus

Lung irritation that can lead to cough and shortness of breath

Side effects from radiation to the abdomen




Poor appetite

Side effects from radiation to the pelvis

Bladder irritation, leading to symptoms like pain or burning with urination and feeling like you have to go often

Irritation of the rectum and anus, which can lead to diarrhea, bleeding, and pain

In women, vaginal irritation and discharge.

Most of these side effects go away after treatment ends, but some are long-term and may never go away completely.

If chemotherapy is given along with radiation, the side effects are often worse.

There are ways to relieve many of these side effects, so it’s important to discuss any changes you notice with your cancer care team.

Chemotherapy for cancer of unknown primary

Chemotherapy (chemo) uses anti-cancer drugs that are usually injected into a vein or taken by mouth. These drugs enter the bloodstream and can reach cancer that has spread. Because chemo reaches all parts of the body, it can sometimes be useful for cancers of unknown primary, as it may help kill cancer cells in areas where they haven’t been detected.

Chemo can be used in a number of situations for cancer of unknown primary (CUP). If your doctor recommends chemo, it’s important that you understand what the goals of your treatment are.

Chemo may be the main treatment for cancers that are clearly advanced and are unlikely to be helped by local treatments such as surgery or radiation therapy. In some cases, such as with cancers that are likely to be germ cell tumors or certain types of lymphomas, it may be very effective in making tumors shrink or even go away altogether. In other cases, chemo may be used to try to relieve symptoms caused by the cancer and may be able to help people live longer.

For cancers that appear to have been removed completely with local therapies such as surgery or radiation, chemo may be added to try to kill any remaining cancer cells in the body.

Chemo drugs are often given in combinations, which are more likely to be effective than giving a single drug alone.

For adenocarcinomas and poorly differentiated cancers where the site of origin is not clear, doctors usually recommend a combination that includes a platinum drug (cisplatin or carboplatin) and a taxane drug (paclitaxel [Taxol®] or docetaxel [Taxotere®]). Other drugs such as gemcitabine (Gemzar®) and etoposide (VP-16) may also be used.

If chemotherapy is to be used for a squamous cell cancer, the most commonly used drugs are cisplatin, 5-fluorouracil (5-FU), and a taxane (paclitaxel or docetaxel).

For neuroendocrine carcinomas that are poorly differentiated, treatment usually includes a platinum drug (cisplatin or carboplatin) and etoposide.

Well-differentiated neuroendocrine cancers are not often the cause of CUP, but may present with liver metastasis and an occult primary. 

Possible side effects of chemotherapy

Chemo drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, like those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects. Some people have many side effects, while others may have few.

The side effects of chemotherapy depend on the type of drugs, the amount taken, and the length of treatment. Some of the most common possible side effects include:

Hair loss

Mouth sores

Loss of appetite

Nausea and vomiting

Low blood cell counts

Chemotherapy often affects the blood-forming cells of the bone marrow, leading to low blood cell counts. This can cause:

Increased chance of infections (low white blood cell counts)

Easy bruising or bleeding (low blood platelet counts)

Fatigue (low red blood cell counts or other reasons)

These side effects are usually short-term and go away after treatment is finished. It’s important to let your health care team know if you have any side effects, as there are often ways to lessen them. For example, drugs can be given to help prevent or reduce nausea and vomiting.

Several other side effects are also possible. Some of these are only seen with certain chemo drugs. Your cancer care team will give you information about the possible side effects of the specific drugs you are getting. It’s important to know the specific side effects that can occur with your drugs so you know what to expect and when to call your doctor.

As with other types of treatment, the chance that the benefits of chemo will outweigh the downsides will depend on a number of factors, including the type and extent of the cancer and a person’s general health before treatment. If you are considering chemo, it’s important to talk to your doctor about the chances that it will be helpful versus the likely side effects you will have.

Hormone therapy for cancer of unknown primary

Some types of cancer grow in response to sex hormones in the body. For example, most breast cancers have proteins called estrogen receptors and/or progesterone receptors on the surface of their cells. These cancers grow faster when exposed to the hormone estrogen. Likewise, most prostate cancers grow in response to male hormones called androgens, such as testosterone.

In cases where a cancer of unknown primary (CUP) is likely to be a breast or prostate cancer, hormone therapy may be an effective way to slow the growth of the cancer, or perhaps even shrink it, and may help you live longer.

For breast cancer, types of hormone therapy include drugs like tamoxifen, LHRH agonists like leuprolide (Lupron®) and goserelin (Zoladex®), and the aromatase inhibitors anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®). These drugs either lower estrogen levels or prevent cancer cells from being able to use it. 

Hormone therapy can also be used to treat prostate cancer. Some commonly used drugs include LHRH agonists such as leuprolide and goserelin, and anti-androgens such as flutamide (Eulexin®) and bicalutamide (Casodex®). These drugs either lower the testosterone level or prevent cancer cells from being able to use it. Surgery to remove the testicles (orchiectomy) is another option. 

Targeted therapy for cancer of unknown primary

Targeted therapy is a newer type of cancer treatment that uses drugs or other substances to identify and attack cancer cells while doing little damage to normal cells. These therapies attack the cancer cells’ inner workings – the programming that makes them different from normal, healthy cells. Each type of targeted therapy works differently, but all alter the way a cancer cell grows, divides, repairs itself, or interacts with other cells.

One target on squamous cell cancers of the head and neck is called epidermal growth factor receptor (EGFR). Cells from many of these cancers have too many copies of EGFR, which helps them grow faster and become more resistant to radiation or chemotherapy (chemo). A drug called cetuximab (Erbitux®) blocks EGFR, and can help patients with squamous cell cancers of the head and neck area. It’s often used along with radiation or chemotherapy (chemo), but it can also be used by itself to treat people whose cancers no longer respond to chemo and who can’t take radiation.

A number of targeted therapy drugs are used to treat breast cancer, including trastuzumab (Herceptin®), pertuzumab (Perjeta®), lapatinib (Tykerb®), and everolimus (Affinitor®). 

Other targeted therapy drugs are used for cancers that start in other areas, and may be helpful in some cases of cancer of unknown primary.

Other drugs for cancer of unknown primary


Bisphosphonates are drugs that are used to help strengthen and reduce the risk of fractures in bones that have been weakened by metastatic cancer. Examples include pamidronate (Aredia®) and zoledronic acid (Zometa®). They are given intravenously (IV). To treat cancer that has spread to bone, they are given once a month.

Bisphosphonates can have side effects, including flu-like symptoms and bone pain. They can also cause kidney problems, so people with kidney problems can’t use them. A rare but very distressing side effect of intravenous bisphosphonates is damage (osteonecrosis) in the jaw bones (ONJ). It can be triggered by having a tooth extraction (removal) while getting treated with the bisphosphonate. ONJ often appears as an open sore in the jaw that won’t heal. It can lead to loss of teeth or infections of the jaw bone. Doctors don’t know why this happens or how to treat it, other than to stop the bisphosphonates. Maintaining good oral hygiene by flossing, brushing, making sure that dentures fit properly, and having regular dental check-ups may help prevent this. Most doctors recommend that patients have a dental check-up and have any tooth or jaw problems treated before they start taking a bisphosphonate.


Like bisphosphonates, denosumab (Prolia®, Xgeva®) is a drug that can be used to strengthen bones and lower the risk of fractures in bones weakened by cancer spread. To treat cancer that has spread to bone, this drug is given as an injection under the skin, once a month.

Side effects include low levels of calcium and phosphate and ONJ. This drug does not cause kidney damage, so it is safe to give to people with kidney problems.


Octreotide (Sandostatin®) is an agent chemically related to a natural hormone, somatostatin. It’s very helpful for some patients with neuroendocrine tumors. If the tumor releases hormones into the bloodstream (which is rare in the poorly differentiated tumors that cause cancer of unknown primary), this drug can stop the hormone release. It can also cause tumors to stop growing or (rarely) to shrink. This drug is available as a short-acting version given as injection 2 to 4 times a day. It’s also available as a long-acting injection that needs to be given only once a month. A similar drug, lanreotide (Somatuline®), is also available. It’s also given as an injection once a month. These drugs are most likely to help treat cancers that show up on somatostatin receptor scintigraphy (OctreoScan).

If treatment for cancer of unknown primary stops working

If cancer keeps growing or comes back after one kind of treatment, it’s possible that another treatment plan might still cure the cancer, or at least shrink it enough to help you live longer and feel better. But when a person has tried many different treatments and the cancer has not gotten any better, the cancer tends to become resistant to all treatment. If this happens, it’s important to weigh the possible limited benefits of a new treatment against the possible downsides. Everyone has their own way of looking at this.

This is likely to be the hardest part of your battle with cancer – when you have been through many medical treatments and nothing’s working anymore. Your doctor may offer you new options, but at some point you may need to consider that treatment is not likely to improve your health or change your outcome or survival.

If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. In many cases, your doctor can estimate how likely it is the cancer will respond to treatment you are considering. For instance, the doctor may say that more chemo or radiation might have about a 1% chance of working. Some people are still tempted to try this. But it’s important to think about and understand your reasons for choosing this plan.

No matter what you decide to do, you need to feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.

Palliative care helps relieve symptoms, but is not expected to cure the disease. It can be given along with cancer treatment, or can even be cancer treatment. The difference is its purpose - the main purpose of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Sometimes, though, the treatments used to control your symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve bone pain caused by cancer that has spread to the bones. Or chemo might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer.

At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it’s given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn’t mean you can’t have treatment for the problems caused by your cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time. 

Staying hopeful is important, too. Your hope for a cure may not be as bright, but there’s still hope for good times with family and friends – times that are filled with happiness and meaning. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life. Now is the time to do some things you’ve always wanted to do and to stop doing the things you no longer want to do. Though the cancer may be beyond your control, there are still choices you can make.

What’s new in research and treatment for cancer of unknown primary?

Research into the causes, diagnosis, and treatment of cancer is being done at many cancer research centers. Scientists are making progress in understanding how changes in a person’s DNA can cause normal cells to develop into cancer. A greater understanding of the gene changes that can occur in cancer is providing insight into why these cells become abnormal. Some of these advances may lead to better diagnosis and treatment of cancer of unknown primary (CUP).


It’s very important that doctors are able to identify the origin of cancers of unknown primary so that the most effective treatments can be used. Immunohistochemistry and other lab tests can be very helpful in this regard, but they are not yet able to tell where all CUPs have started. Newer lab tests now becoming available will help classify CUP more precisely and predict a patient’s prognosis and response to treatment.

Hopefully at some point in the future, the number of cancers of unknown primary will drop dramatically, as doctors will be able to test tumor samples and determine what types of cancer they are.


Because CUP represents a number of different types of cancer, it’s unlikely that a single treatment breakthrough will benefit all people with CUP. Still, progress in treating some of the more common types of cancer is likely to benefit people with CUP as well, especially if the cancers can be classified more accurately.

Some newer drugs called targeted therapies are being studied. These drugs have more selective effects than chemotherapy (chemo). Some of these, such as bevacizumab (Avastin®) and erlotinib (Tarceva®), are available to treat other cancers and have shown some activity in CUP. Clinical trials are being done to help determine who may benefit from targeted drugs and what drugs and combinations are best.

Cancer cells from CUP are sometimes tested in a lab to try to see which chemo drugs will be likely to work. Unfortunately, these tests don’t always do a good job of predicting the right chemo drugs. Many doctors don’t find them very helpful.

Many patients with cancer of unknown primary face a serious prognosis, so the need for advances in treatment is obvious. Clinical trials of new treatments are essential if progress is to occur. Some of these trials are testing new chemo drugs, new drug combinations, and new ways to give these drugs. Other clinical trials are studying new approaches to treatment, such as biological therapy, immunotherapy, and gene therapy. Because CUP is a very diverse category of many types of cancers, progress against CUP is likely to depend on continued progress toward understanding the molecular basis of all cancers.

Recent News and Articles Obesity primes the colon for cancer, study finds Common Respiratory Diseases Tied to Lung Cancer Risk