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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. On the other hand, you may feel relieved that the tests are over and that the focus can now be on treating the cancer.

Your treatment plan

The treatment recommended by your doctors will depend on:

  • where the secondary cancer is in the body and how far it has spread
  • where they think the cancer started
  • how quickly the cancer seems to be growing
  • how you are feeling (your symptoms)
  • your general health, age and treatment preferences
  • what treatments are currently available and whether there are any newer treatments available on clinical trials
  • the aim of treatment (whether to remove as much of the cancer as possible, slow the cancer’s growth or relieve symptoms).

The most common treatment for CUP is chemotherapy, and many people also have radiation therapy and surgery. Some cancers may respond to hormone  therapy, targeted therapy or immunotherapy. Your doctor may suggest a combination of treatments.

Chemotherapy uses drugs to kill cancer cells or slow their growth. Medical oncologists and some other specialists prescribe chemotherapy to shrink a cancer and relieve symptoms. It can also be used together with radiation therapy or surgery to try to kill a collection of cancer cells in the body.

How chemotherapy is given – Generally, chemotherapy is given through a drip inserted into a vein (intravenously), but some types are taken by mouth as tablets. As different cancer cells respond to different chemotherapy drugs, you may have a combination of drugs.

Chemotherapy is commonly given as a period of treatment followed by a break. This is called a cycle. The length of the cycle depends on the drugs  used. Usually, you will have chemotherapy during day visits to a hospital or treatment centre. Sometimes a short stay in hospital is needed.

Number of sessions – The total number of treatment cycles you have depends on your situation. With CUP, after 2 or 3 cycles you will usually have imaging scans to test how the cancer is responding to the drugs. The results will let you weigh up the benefits of continuing the treatment against the effects on your quality of life. It may also mean a change in treatment if the chemotherapy is not shrinking the cancer.

Side effects of chemotherapy

Most chemotherapy drugs cause side effects. These 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 body’s immune system, making it harder 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 go to the nearest hospital emergency department 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.

It is important to tell your treatment team about any side effects you have from drug therapies. Side effects can be better managed when reported early. You may be given medicine to prevent or reduce side effects. Sometimes, your doctor may delay treatment or reduce the dose to lessen side effects.

Download our booklet ‘Understanding Chemotherapy’

Hormones are substances that occur naturally in the body. Some cancers depend on hormones to grow (e.g. oestrogen may help breast cancer grow). Hormone therapy aims to lower the amount of hormones in the body in order to slow or stop the cancer’s growth. The treatment may be given as tablets you swallow or injections. If tests show that the CUP may have started as a cancer that is hormone dependent, your doctor might suggest hormone therapy. 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. Common 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.

It is important to tell your treatment team about any side effects you have from drug therapies. Side effects can be better managed when reported early. You may be given medicine to prevent or reduce side effects. Sometimes, your doctor may delay treatment or reduce the dose to lessen side effects.

This is a type of drug therapy that attacks specific features of cancer cells to stop the cancer growing and spreading. Many targeted therapy drugs are given by mouth as tablets, but some are given by injection.

Only a small number of CUP tumours will be suitable for targeted therapy. Your doctors will need to test the cancer to see if the cells have a particular cell change that is helping the cancer grow.

Side effects of targeted therapy

Targeted therapy drugs minimise harm to healthy cells, but they can still have side effects. These side effects vary greatly depending on the drug used and how your body responds. Common side effects of targeted therapy include skin rashes, fever, tiredness, joint aches, nausea, diarrhoea, bleeding and bruising, and high blood pressure.

It is important to tell your treatment team about any side effects you have from drug therapies. Side effects can be better managed when reported early. You may be given medicine to prevent or reduce side effects. Sometimes, your doctor may delay treatment or reduce the dose to lessen side effects.

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.

The usefulness of immunotherapy for CUP is still being tested, so it is not funded on the Pharmaceutical Benefits Scheme (PBS) for CUP. However, it may be accessed on the PBS if test results strongly suggest that you have one of the cancer types for which it is funded (e.g. lung, kidney or bladder cancer). Ask your specialist for more information.

It is important to tell your treatment team about any side effects you have from drug therapies. Side effects can be better managed when reported early. You may be given medicine to prevent or reduce side effects. Sometimes, your doctor may delay treatment or reduce the dose to lessen side effects.

Download our fact sheet ‘Understanding Immunotherapy’

Also known as radiotherapy, radiation therapy uses a controlled dose of 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 pain, bleeding, difficulty swallowing, bowel blockages, shortness of breath, and tumours pressing on blood vessels or nerves or within bones.

Having radiation therapy – 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 usually have a 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, although it can be uncomfortable lying on a hard treatment table.

Number of sessions – 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.

Chemoradiation – If squamous cell carcinoma spreads to the lymph nodes (e.g. in the neck or groin area), you may be offered a combination of chemotherapy and radiation therapy. This treatment is known as chemoradiation. It may be given for up to 7 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. Nausea or altered sense of taste can sometimes occur. Your skin may become dry and itchy in the area treated, look red or sunburnt and feel sore.

Side effects tend to develop as you go through radiation therapy, and most improve or go away in the weeks after you finish treatment. Talk to your doctor or nurse about ways to manage any side effects you have.

Download our booklet ‘Understanding Radiation Therapy’

Surgery removes cancer from the body. It is mostly used if cancer is found at an early stage. If CUP has already spread to a number of places in the  body, surgery may not be the best treatment. If surgery is used, it may remove only some of the cancer. Surgery is often followed by radiation therapy or chemotherapy to kill or shrink any cancer cells left in the body.

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 lymph node 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

After surgery, you may have some side effects. These will depend on the type of operation you have. Your surgeon will talk to you about the risks and complications of your procedure. These may include infection, bleeding and blood clots. You may experience pain after surgery, but this is often temporary. Talk to your doctor or nurse about pain relief.

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’

Download our fact sheet ‘Understanding Lymphoedema’

Most people with CUP receive palliative treatment. This is treatment that aims to slow the spread of cancer and relieve symptoms without trying to cure the disease.

Cancer treatments such as surgery, radiation therapy, chemotherapy or other medicines are often given palliatively. It is possible that palliative  treatment may make you feel better and also help you live longer.

You might think that palliative treatment is only for people at the end of their life, but it may help at any stage of advanced cancer. It is about living for as long as possible in the most satisfying way you can.

What is palliative care?

Palliative care supports the needs of people with a life-limiting illness in a holistic way.

The main goal is to help you maintain your quality of life by dealing with your physical, emotional, cultural, spiritual and social needs. Palliative care also provides support to families and carers.

Specialist palliative care services don’t prescribe cancer treatments, but help people with CUP manage symptoms related to the cancer. They can also help you work out how to live in the most fulfilling way you can. 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 September 2022 by the following expert content reviewers: Prof Chris Karapetis, Network Clinical Director (Cancer Services), Southern Adelaide Local Health Network, Head, Department of Medical Oncology, and Director, Clinical Research in Medical Oncology, Flinders Medical Centre and Flinders University, SA; Dr Amey Aurangabadkar, Radiologist, Illawarra Radiology Group, NSW; Clare Brophy, Consumer; Prof Katherine Clark, Clinical Director of Palliative Care, NSLHD Supportive and Palliative Care Network, Northern Sydney Cancer Centre, Royal North Shore Hospital, NSW; Prof Wendy Cooper, Senior Staff Specialist, Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, NSW; A/Prof Richard Gallagher, Head and Neck Surgeon, Director of Cancer Services and Head and Neck Cancer Services, St Vincent’s Health Network, NSW; Dr Chloe Georgiou, Oncology Research Fellow, Australian Rare Cancer Portal, and Oncology Trials Fellow, Bendigo Health Cancer Centre, VIC; Dr Susan Harden, Radiation Oncologist, Peter MacCallum Cancer Centre, VIC; Justin Hargreaves, Medical Oncology Nurse Practitioner, Bendigo Health Cancer Centre, VIC; Dr Laura Kirsten, Principal Clinical Psychologist, Nepean Cancer Care Centre, NSW; Prof Linda Mileshkin, Medical Oncologist, Peter MacCallum Cancer Centre, VIC; Caitriona Nienaber, 13 11 20 Consultant, Cancer Council WA.