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Treatment for cancer of unknown primary

When tests have been unable to find the primary cancer, you will be given a diagnosis of CUP. This is often a difficult time and it can be hard to accept that the primary site cannot be found. Some people may feel relieved that the tests are over and that the focus can now be on treatment options. 

Your doctors will recommend treatment based on:

  • what will give you the best outcome
  • the location of the secondary cancer
  • test results
  • where in the body they suspect the cancer started
  • your general health
  • your preferences.

The most common treatment for CUP is chemotherapy. You may also have hormone therapy, targeted therapy, radiation therapy or surgery. Different types of treatment may be combined.

For many people, CUP is diagnosed at an advanced stage and treatment is unlikely to cure it. However, treatment may be able to control the cancer and improve your symptoms. It is possible that treatment may make you feel better and also help you live longer. This is called palliative treatment.

Chemotherapy is the use of drugs to kill or slow down the growth of cancer cells. Medical oncologists and some other specialists prescribe chemotherapy to relieve symptoms caused by the cancer. It can also be used together with radiation therapy or surgery to try to kill any local collections of cancer cells in the body. As different cancer cells respond to different chemotherapy drugs, you may be given a combination of drugs.

You will usually be given the chemotherapy drugs by drip into a vein (intravenously), but some types are taken by mouth as tablets. The drugs circulate through the bloodstream and can kill cancer cells throughout the body (systemic treatment).

Chemotherapy is given in courses known as cycles. Typically, you will have chemotherapy as an outpatient, but sometimes a short stay in hospital is needed. Each cycle is followed by a recovery period. The number of treatment cycles you have depends on your situation. With CUP, it is recommended that your doctors test how the cancer responds to the chemotherapy after two or three cycles. This will allow you to weigh up the benefits of continuing against the effects on your quality of life.

Side effects of chemotherapy

Most chemotherapy drugs cause side effects. Side effects are usually temporary, and can be prevented or reduced. The most common side effects include feeling sick (nausea), vomiting, mouth sores, tiredness, loss of appetite, diarrhoea or constipation, and some thinning or loss of hair from your body and head.

Chemotherapy weakens the immune system, making it harder for your body to fight infections. You will have regular blood tests to check your immune system. If your temperature rises to 38°C or above, contact your medical team or hospital immediately.

The side effects of some chemotherapy drugs can be longer lasting or permanent (e.g. damage to the heart or nerves). Ask your doctor to explain the potential risks and benefits of the chemotherapy recommended for you.

Download our booklet ‘Understanding Chemotherapy’

Hormones are substances that occur naturally in the body. Some hormones can stimulate certain cancers to grow – for example, oestrogen and breast cancer. Hormone therapy uses hormones made in a laboratory (synthetic hormones) to block the effect of these natural hormones that are helping the cancer to grow.

If tests show that the CUP may have started as a cancer that is hormone dependent, your doctor might suggest hormone therapy. The treatment may be given as tablets or injections. It is sometimes used with other treatments.

Side effects of hormone therapy

The side effects of hormone therapy will vary depending on the hormones you are given. General side effects include tiredness, nausea, appetite changes, weight gain, mood changes, pain in the joints, thinning of the bones (osteoporosis), hot flushes and erection problems.

Targeted therapy is a type of cancer drug treatment that attacks specific features of cancer cells to stop the cancer growing and spreading. Clinical trials are testing combinations of chemotherapy and targeted therapy drugs to see whether they work for CUP.

Most targeted therapy drugs are injected into a vein, but some are given by mouth as tablets.

Side effects of targeted therapy

Targeted therapy drugs minimise harm to healthy cells, but they can still have side effects. These vary depending on the drug used, but may include fatigue, mouth ulcers, changes in appetite, fevers, allergic reactions, skin rashes, and diarrhoea.

Download our fact sheet ‘Understanding Targeted Therapy’

Immunotherapy uses the body’s own immune system to fight cancer. Sometimes the results of specialised tests on a CUP tumour may suggest that immunotherapy could help to treat the cancer. However, immunotherapy drugs currently approved for other cancers are still being tested within clinical trials to work out how often they help people with CUP. You can ask your specialist for more information.

Download our fact sheet ‘Understanding Immunotherapy’

Radiation therapy, also known as radiotherapy, uses targeted radiation to kill or damage cancer cells. The radiation is usually in the form of x-ray beams. Most people with CUP have radiation therapy to relieve symptoms, such as bleeding, difficulty swallowing, shortness of breath, blockages in the bowel, tumours pressing on blood vessels or nerves, and pain caused by cancer spreading to the bones.

People with CUP are most likely to have external beam radiation therapy (EBRT), which is given from a machine outside the body. To help plan treatment, you will have an x-ray or CT scan of the treatment area. To ensure that the same area is treated each time, the radiation therapist will make a few small dots (tattoos) on your skin that may be temporary or permanent. Radiation treatments are painless. The total number of treatments and when you have them will depend on your situation. You might need only a single treatment, or you may need them every weekday for several weeks.

Some people with localised squamous cell carcinoma in the lymph nodes of the neck may be offered a combination of chemotherapy and radiation therapy. This treatment is known as chemoradiation. It may be given for up to seven weeks.

Side effects of radiation therapy

The side effects will depend on the area of the body being treated and the dose of radiation. The most common side effect is fatigue. Radiation therapy can also make your skin dry and itchy in the area treated. Your skin may look red or sunburnt and feel sore – talk to your radiation therapy team about creams and other ways to manage this.

Side effects tend to develop as you go through treatment, and most improve or go away in the weeks after treatment is finished. Talk to your doctor or nurse about ways to manage them.

Download our booklet ‘Understanding Radiation Therapy’

Surgery removes cancer from the body. It is mostly used if cancer is found at an early stage, and is often followed by radiation therapy or chemotherapy to kill or reduce any cancer cells left in the body.

For many people, CUP has already spread to a number of places in the body, so surgery may not be the best treatment. If surgery is used, it may remove only some of the cancer. If the cancer is found only in the lymph nodes in the neck, underarm or groin, it may be possible to remove all of it with an operation. This is called a neck dissection or lymphadenectomy.

Sometimes surgery can help with symptoms – for example, to relieve pain caused by the tumour pressing on a nerve or organ.

Side effects of surgery

Some people experience pain after surgery, but this is often temporary. Talk to your doctor or nurse about painkillers. If lymph nodes have been removed, you may develop lymphoedema. This is swelling caused by a build-up of lymph fluid in part of the body, usually in an arm or leg. For more details, speak to your nurse, visit or call Cancer Council 13 11 20.

Download our booklet ‘Understanding Surgery’

Many people with CUP receive palliative treatment. This is treatment that aims to slow the spread of cancer and manage symptoms without trying to cure the disease. It can be used at any stage of advanced cancer to improve quality of life and does not mean giving up hope. Rather, it is about living for as long as possible in the most satisfying way you can. Some people receive palliative treatment as well as active treatment of the cancer.

Palliative treatment is one aspect of palliative care, in which a team of health professionals aims to meet your physical, emotional, cultural, social and spiritual needs. The team also provides support to families and carers. Specialist palliative care services see people with complex needs and can also advise other health professionals. Contacting a specialist palliative care service soon after diagnosis gives them the chance to get to know you. You can ask your doctor for a referral.

Download our booklet ‘Understanding Palliative Care’

Download our booklet ‘Living with Advanced Cancer’

Featured resources

Cancer of Unknown Primary - Your guide to best cancer care

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Understanding Cancer of Unknown Primary

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This information is reviewed by

This information was last updated June 2020 by the following expert content reviewers: Prof Linda Mileshkin, Medical Oncologist, Clinical Researcher, Peter MacCallum Cancer Centre, VIC; Christine Bradfield, Consumer; Cindy Bryant, Consumer; Dr Maria Cigolini, Head, Department of Palliative Medicine, Royal Prince Alfred Hospital, and Clinical Lecturer, The University of Sydney, NSW; Mary Duffy, Advanced Practice Nurse and Nurse Coordinator, Lung Service, Peter MacCallum Cancer Centre, VIC; Karen Hall, 13 11 20 Consultant, Cancer Council SA; Dr Andrew Oar, Radiation Oncologist, Icon Cancer Centre, Gold Coast University Hospital, QLD; Dr Siobhan O’Neill, Medical Oncologist, Nelune Comprehensive Cancer Centre, NSW; Prof Penelope Schofield, Department of Psychological Sciences and the Iverson Health Innovation Research Institute, Swinburne University of Technology, and Head, Behavioural Science in Cancer, Peter MacCallum Cancer Centre, VIC; Frank Stoss, Consumer.