Investigating an Abnormal Finding: Investigations for Malignancy of Unknown Origin (MUO)

Patient and Family Information

Your test results may have shown some abnormalities. These may represent changes to normal appearances outside the expected results and need to be investigated to determine what might have caused this, which includes ruling out the possibility of cancer.

Malignancy of unknown origin (MUO) is when there is a suspicion that you might have cancer, but we are not certain where it has started or what type it is. You will usually have had a scan or test that shows an abnormality and we need to rule out cancer.

Our first task is to find out whether or not you have cancer.

We know that having investigations for cancer can be a worrying time. You might feel that there is a lot of waiting and uncertainty.

You will need one or more tests before we know whether or not you have cancer and, if so, what type of cancer you have.

In most cases, it is clear where in the body the cancer has started. However, sometimes we find a cancer that has spread around the body without a clear starting point.

If we do find out where your cancer started, your care will be handed over to a specialist Oncology team. For example, if we believe your cancer started in the lung, you will be treated by the lung cancer team. If we cannot find out where the cancer has started, your care will be referred to the cancer of unknown primary team (CUP).

Cancer of Unknown Primary

This leaflet is for patients who have a provisional diagnosis known as Cancer of Unknown Primary (CUP). This leaflet explains what is meant by CUP and details what investigations and potential treatments you may receive. CUP means that a secondary cancer has been found but as yet we have not been able to identify the primary cancer.

• Primary cancer is usually named after the part of the body where a cancer has started
• Secondary cancer means that the cancer has spread to another site, other than where it originated. A secondary cancer can sometimes be known as a metastasis

What is CUP?

CUP is a general term that covers many different types of cancer. It affects about 3-5% of people diagnosed with cancer.

People with CUP often have more than one secondary cancer.
It is more common in older people but younger people can also get CUP.

Your doctor may suspect you have CUP if early tests don’t find the primary cancer, but the diagnosis won’t be certain until you’ve had all the appropriate tests. Cancer doctors will try to find the primary cancer, because it helps them plan the most effective treatment for you. Some people with suspected CUP may be too unwell to have lots of tests.

Sometimes, tests will find the primary cancer. When this happens, the cancer is no longer called CUP. It is named after the primary cancer and treated accordingly.

Even when the primary cancer cannot be found, your specialist may be able to suggest a probable part of the body where the cancer has started. This will be based on your specialist’s experience, where the secondary cancers are, your symptoms and the test results.

Why the primary cancer can’t be found

There are different reasons why a primary cancer can’t always be found:

• The secondary cancer or cancers have grown and spread very quickly, but the primary is still too small to be picked up on scans
• The cancer has been growing in more than one area of the body for some time, making it difficult to see where it started
• The primary cancer might have disappeared, even though it has spread to other parts of the body

Symptoms of cancer of unknown primary

People affected by advanced cancer may have some of these symptoms:

• Unexplained weight loss
• Loss of appetite and/or feeling sick
• Feeling extremely tired all the time
• Looking pale
• Persistent pain
• A cough that doesn’t go away
• Breathlessness caused by fluid collecting around the lungs (pleural effusion)
• Yellowing of the skin and eyes (jaundice)
• Swelling of your tummy (ascites)
• Your lymph glands (glands in your neck, groin or under arms) may be swollen and feel hard or cause pain if they’re pressing on tissue or nerves nearby
• Headache, confusion and loss of balance
• Bowel changes
• Nausea and vomiting

Investigation / tests

Having tests can take up a lot of your energy and time. You will only be put through tests if they are likely to make a difference to your overall treatment or care.

We will endeavour at all times to include you and your family in decisions regarding further tests and the benefits of treatment.

Common tests are:

• X-rays
• CT scan (computerised tomography), this takes lots of x-rays of an area of your body to create a detailed picture. The scan may last 10-30 minutes. You may be given a drink or an injection of dye beforehand
• MRI scan (magnetic resonance imaging), this uses magnetism to build up a set of pictures instead of x-rays. You will be asked to lie flat inside the tunnel scanner, for sometimes up to an hour
• PET-CT scan (positron emission tomography) measures important body functions such as metabolism by injecting a small amount of a radioactive tracer together with CT images to often give more detailed information. There will be a list of instructions provided for you as to things to do before and after
• Ultrasound scan, this is using sound waves to create a picture of an area inside your body. It involves putting gel onto your abdomen and then rubbing a small device over the area
• Blood tests including tumour markers, taking a small sample of blood from your arm
• Biopsy, this involves taking a small tissue sample from the cancer. If you require a biopsy, you will be given more information on the procedure

Whole Genome Sequencing (WGS)

Whole Genome Sequencing is a special test that looks at all of your DNA. It can sometimes give doctors extra clues about:

• Where your cancer started (the “primary”).
• What might be causing the cancer to grow.
• Which treatments could work best for you.

This test is not suitable for everyone with CUP. Whether it is an option depends on things like the type of biopsy you’ve had, the amount of sample available, and your overall health.

Ask your hospital team if Whole Genome Sequencing is right for you. They can explain what the test involves and how it may help guide your care.

Making Treatment Decisions

Often, when the diagnosis of cancer is made, everything seems to happen very fast. Deciding on different treatment options can be difficult, so make sure to check with your doctor the best treatment option for you. Ask when your treatment should start and take as much time as needed before making a decision.

Gathering information about the disease process, the treatment options and their potential side effects can assist you in this decision. Discussing the options with family and friends can also play an important role on deciding what is right for you and your personal lifestyle. At any stage it is possible to stop or decline a treatment. Some people choose to start treatment even if it may be minimally effective and some people decide not to commence extensive chemotherapy or radiotherapy treatments at all.

When a decision is made to commence treatment for CUP there is a variety of options available. Some people, although disappointed that no primary has been found, are relieved that the tests are over and treatment can commence. Your treatment will be based on numerous factors including:

• The location and form of your CUP
• What will give you the best outcome
• Test results
• Your preferences
• Your general health
• How likely it is to be a certain type of cancer

Most patients with CUP will have chemotherapy. Other treatments include radiotherapy, hormone therapy, surgery or targeted therapies. It is common to have a combination of therapies.

It is important to note that for most people, CUP is diagnosed at an advanced stage. Treatment may be unable to cure it but is aimed at controlling it and improving symptoms and maintaining quality of life.

Treatments

CUP is a cancer that has already spread to other parts of the body and treatment for CUP is given to improve symptoms and prolong life but does not usually cure it. The aims of treatment would be to slow down the growth of the cancer, relieve any symptoms and help you live longer. This is referred to as palliative treatment.

Chemotherapy, radiotherapy, surgery, steroids and other anti-cancer treatments can all be used for palliative treatment.

Palliative treatment options can include one or more of the following:

• Surgery – this may be before, during or after other treatments
• Drug therapies such as chemotherapy and immunotherapy. The general term for these is systemic anti-cancer therapies (SACT)
• Radiotherapy
• Steroids

Deciding about treatment

Your doctor will discuss your treatment options with you so you can decide what is right for you.

Sometimes the disadvantages of treatment may outweigh the benefits. For example, your body may not be strong enough to cope with cancer treatments.

Sometimes people with CUP decide not to have treatment.

If you are not well enough for cancer treatment – or you decide not to have treatment – we will do everything we can to keep you comfortable and to help you cope with your symptoms.

Systemic anti-cancer therapy (SACT)

SACT is a term used to describe the different drug therapies for cancer. These include:

• Chemotherapy – which aims to kill cancer cells
• Immunotherapy – which aims to train your immune system to attack cancer
• Targeted therapies – which aim to target the DNA and cell changes that cause cancer. For example, BRAF targeted therapy which blocks a protein linked to cancer cells.

Radiotherapy

Palliative radiotherapy may be used if your tumour is causing localised symptoms such as pain. We use different types of radiotherapy, depending on the size, location and stage of the cancer.

The palliative radiotherapy treatments we offer include:

• Traditional external beam radiotherapy – where radiation is delivered from outside the body
• Stereotactic ablative radiotherapy (SABR) – a way of very precisely targeting radiotherapy to certain cancers

Clinical trials

Research and trials of new cancer treatments are an important part of our work. Your consultant will tell you about any clinical trials that may be suitable for you.

If you are interested in taking part in a clinical trial, speak to your doctor. They are in the best position to advise you about any trials that may be suitable for you and your cancer

Factors that influence treatment options are:

• Extent and location of secondary cancer (metastases)
• Potential benefits and risks of treatment for you
• Your general health and fitness
• Your wishes and consent

Although you may not be investigated further or offered any treatment, the team will always ensure that you have the optimum care and input required to keep you comfortable. Supportive care, such as medications for example anti-sickness, painkillers and steroids are an important part of treatment for people with CUP. As well as medication, you may be referred to the palliative care team and district nurses for further psychological and symptom control support, in addition to information regarding support groups and complementary therapies.

The doctor will discuss all available treatments with you and talk through the potential risks, benefits and side effects.

Multi-Disciplinary Team meetings

All patients with a diagnosis of cancer are discussed at an appropriate Multi-Disciplinary Team (MDT) meeting. These meetings involve a group of health professionals who specialise in your particular diagnosis and a plan of action will be made. The MDT should also assign you a key worker, most commonly the clinical nurse specialist, who is a clear point of contact and provides ongoing support.

Prognosis

A prognosis is the expected time course of an illness. Each patient and presentation may have a different prognosis. It is best to discuss your individual case with your treatment team. Unfortunately, it is never possible to predict the exact outcome of any disease process, especially with cancer.

Prognosis is affected by the growth rate and position of the tumour, the response to treatment and many other factors such as age, fitness and any other medical conditions you may have. Although it is currently impossible to cure most cancers of unknown primary, some forms of CUP can be controlled for months or years.

There are some forms of localised CUP (e.g. a lymph node in the groin) that can be cured with surgery and extensive chemo-radiation treatments. Regardless of the prognosis, cancer and palliative care teams can provide medication to minimise pain and suffering and maximise quality of life. See the palliative care section for further information.

Your CUP doctor is:

Your CUP Clinical Lead Nurse is:

Other contact details

The Macmillan Information Centres can provide:

• Booklets, advice and information free of charge
• Financial advice from a benefits advisor
• Information regarding support groups
• Complementary therapy services

Useful organisations

• Jo’s friends CUP Foundation (opens in a new tab)
• World CUP Alliance (opens in a new tab)
• Macmillan Cancer Support 0808 808 00 00
• NHS Choices (opens in a new tab)
• Cancer Research UK (opens in a new tab)
• Age UK (opens in a new tab)
• Detailed info about money and deb (opens in a new tab)t
• Citizen’s advice (opens in a new tab)
• Carers UK (opens in a new tab)

This patient information leaflet has been developed by East of England Cancer Alliance CUP network