When tests have been unable to find the primary cancer, a diagnosis of CUP is given. 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 radiation therapy, hormone therapy, surgery or targeted therapy. 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.

“I have found it complex to talk to people about my cancer. I can explain it, but they find it hard to understand. It does seem incomprehensible to have a cancer that has spread but no named starting point.” – Jane

Chemotherapy

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 in combination 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 have a combination of drugs.

You will usually have 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 required. 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 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.

Radiation therapy

Radiation therapy, also known as radiotherapy, uses targeted radiation such as x-ray beams to kill cancer cells. 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.

To help plan treatment, you will have an x-ray 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, in some cases, permanent. You may have external or internal radiation therapy. External beam radiation therapy (EBRT) is given from a machine outside the body. For internal radiation therapy, a radiation source is placed inside the body on or near the cancer. Radiation treatments are painless. The total number of treatments and their duration will depend on your situation. You might need only a couple of treatments, 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 have a combination of chemotherapy and radiation therapy (chemoradiation).

For more information, see chemotherapy, radiation therapy or surgery, or call Cancer Council 13 11 20.

Side effects of radiation therapy

The side effects will depend on the area of the body being treated and the dose of radiation. General side effects include fatigue, loss of appetite, diarrhoea, and shortness of breath. Radiation therapy can also make your skin dry and itchy in the area treated. Your skin may look red or sunburnt.

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.

Hormone therapy

Hormones are substances that occur naturally in the body, but some cancers can be stimulated by particular hormones – for example, breast cancer by oestrogen. Hormone therapy uses hormones made in a laboratory (synthetic) to block the effect of the 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 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, hot flushes and, in men, erection problems.

Surgery

Surgery removes cancer from the body. It is commonly used if cancer is found at an early stage. As CUP has already spread beyond the site where it started, surgery may not be the best treatment. If used, it may remove only some of the cancer. Surgery may be followed by radiation therapy or chemotherapy to kill any cancer cells left in the body. If the cancer is found in the lymph nodes in the neck, underarm or groin, it may be possible to remove 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 lymphoedema.org.au, or see Understanding Lymphoedema.

Targeted therapy

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.

Treatments under development

Immunotherapy focuses on using the body's own immune system to fight cancer. The immunotherapy drugs currently approved for other cancers have not been tested for CUP. Ask your specialist for more information or see Understanding Immunotherapy.

Gene therapy is the delivery of tiny fragments of DNA, called genes, into cancer cells. These genes can regulate the way a cancer grows, and may help turn off the cancer cells. This treatment is experimental and is not yet a standard treatment for CUP.

Palliative treatment

Many people with CUP receive palliative treatment, which can be used at any stage of advanced cancer to improve quality of life. Palliative treatment aims to slow the spread of cancer and manage symptoms without trying to cure the disease.

Palliative treatment is one aspect of palliative care, in which a team of health professionals aim to meet your physical, practical, emotional, spiritual and social 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 care professionals. Contacting a specialist palliative care service soon after diagnosis gives them the opportunity to get to know you, your family and your circumstances. You can ask your treating doctor for a referral. See Understanding Palliative Care and Living with Advanced Cancer or call Cancer Council 13 11 20.

Key points

• Treatment can help control the symptoms of CUP, but it may not cure the disease.
• CUP treatment may include chemotherapy, radiation therapy, hormone therapy, surgery and targeted therapy. The best treatment for you will depend on the type of cancer cell, the suspected primary site, the location of the secondary cancer(s), and your general health.
• Chemotherapy treats cancer with drugs. Common side effects include nausea, vomiting, mouth sores, tiredness, loss of appetite, diarrhoea or constipation, and hair loss. There may also be an increased risk of infections. Side effects depend on what kinds of drugs you are given.
• Radiation therapy also called radiotherapy uses radiation such as x-ray beams to kill cancer cells. It may cause side effects such as skin irritation or shortness of breath. Other side effects include loss of appetite, diarrhoea and tiredness.
• Hormone therapy is sometimes used to treat CUP by slowing the growth of the cancer or shrinking it.
• Surgery may be used to remove tumours or lymph nodes in the neck, underarm or groin. It's not always a treatment option for CUP, and sometimes only part of the cancer can be removed.
• Targeted therapy is a new group of cancer drugs. Clinical trials are testing their usefulness for CUP.
• The aim of palliative treatment is to manage symptoms to improve quality of life. If possible, get in touch with the palliative care team early.

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