Research into cancer of unknown primary

Researchers around the world are looking at better ways to monitor and treat cancer of unknown primary (CUP). Go to Cancer Research UK’s clinical trials database if you are looking for a trial for CUP in the UK. You need to talk to your specialist if there are any trials that you think you might be able to take part in.

Some of the trials on this page have now stopped recruiting people. It takes time before the results are available. This is because the trial team follow the patients for a period of time and collect and analyse the results. We have included this ongoing research to give examples of the type of research being carried out in CUP. 

Research and clinical trials

All cancer treatments must be fully researched before they can be used for everyone. This is so we can be sure that:

• they work

• they work better than the treatments already available

• they are safe

To make sure the research is accurate, each trial has certain entry conditions for who can take part. These are different for each trial.

Hospitals do not take part in every clinical trial. Some trials are only done in a small number of hospitals, or in one area of the country. You may need to travel quite far if you take part in these trials. 

Research into the diagnosis of CUP

Knowing where the cancer started (the primary tumour) helps doctors plan the treatment. So, researchers are looking at how cancer tests can improve the diagnosis of CUP. They hope this might improve the outlook for people.   

Doctors can often tell where a cancer started by looking at the cancer cells under a microscope. These doctors are called pathologists. But sometimes this does not give enough information. So, they may use other techniques such as:

• immunohistochemistry (IHC)
• genetic and molecular profiling

Immunohistochemistry (IHC)

IHC is a way of staining tissue to find proteins (antigens). It can sometimes tell what type of cancer you have, even when other tests haven’t found out the primary cancer.

Genetic and molecular profiling

Researchers are testing techniques called gene expression profiling and molecular profiling. Both techniques look at the genes  in the secondary cancer, to try to find where the cancer started. 

Looking at the genes or genetic profiling of the cancer helps your doctor. They can then decide if a targeted drug is suitable for your cancer. 

Some studies have shown that genetic profiling can help to tell where the cancer started. At the moment we know it may help some people but not everyone diagnosed with CUP. 

We need more research to see if having these tests at diagnosis could improve treatment and survival.

Research into treatment of CUP

There are some clinical trials looking at treatment for CUP. Researchers are mainly looking at targeted cancer drugs. You may have these drugs alone or in combination.

SACT (Systemic Anti-Cancer Treatment)

Chemotherapy and immunotherapy drugs may be used in the treatment of CUP. Clinical trials are looking at giving drugs on their own or in combination. They want to find out which is the best way to treat CUP.

Targeted cancer drugs

Targeted cancer drugs are one of the main treatments for some types of cancer. They work by targeting differences that a cancer cell has that helps them to survive and grow. There are many different types of targeted drugs. Currently these drugs are not routinely used to treat CUP. They are being looked at in clinical trials. 

Some of the targeted cancer drugs that doctors are looking at for CUP include: 

• alectinib

• vismodegib

• olaparib

• erlotinib and bevacizumab

• vemurafenib and cobimetinib

• trastuzumab

• pembrolizumab

The DETERMINE trial is looking at matching targeted treatment to people who have a rare cancer.

Research into coping with CUP

A small study looked at the experiences of people affected by CUP. Researchers found out that people with CUP have similar issues to people with other cancer types, such as anxiety. But they found they had them to a much greater extent.

The trial team found that many people had not heard of CUP before their diagnosis. They found it difficult to get information. And they felt anxious that some medical teams couldn’t agree on the best treatment option.

They also found that people with CUP often got referred from one medical team to another. People often lost contact with their specialist nurse as they moved between teams. This can make it more difficult for people and their families to cope.