Decorative image


Read about research into the diagnosis, treatment and living with cancer of unknown primary (CUP).

Researchers are trying to improve the diagnosis of CUP. They are also trying to improve treatment and looking at the experiences of people living with CUP.


Knowing where the cancer started (the primary tumour) helps doctors plan the most effective treatment. So, researchers are looking at how cancer tests can improve the diagnosis of CUP.  

Doctors often use CT scans and MRI scans, to try to find where the cancer started. Studies have shown that PET-CT scans are also helpful, particularly when looking for cancers in the head and neck area.

Researchers are looking to see if PET-CT scans are more helpful than the usual scans. They also want to know if PET-CT scans can reduce the number of tests people have.

Advances in technology such as PET-MRI scans may also help to improve diagnosis for people with CUP.

Doctors in the laboratory (pathologists) can often tell which type of cancer cell they are looking at by using a microscope. But sometimes this does not give enough information. So, they may use other techniques such as:

  • immunohistochemistry (IHC)
  • genetic profiling

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 the primary cancer.

Genetic profiling

Researchers are testing newer techniques called gene expression profiling and molecular profiling. Gene expression profiling looks at the genes in the secondary cancer, to try to find where the cancer started. Molecular profiling also looks at the genes in the tissue sample.

These tests are not yet available on the NHS. You may have them as part of a clinical trial.  

Studies have shown that genetic profiling can predict where the cancer started for most people. So, this may be helpful in cases where IHC doesn’t identify the primary cancer. But doctors want to do more research to see if having these tests improves survival for people with CUP.

Genetic profiling could also help doctors decide on treatment, particularly with new targeted cancer drugs.

An American study asked about 250 people with CUP to give a tissue sample. Researchers tested the tissue sample using molecular profiling and could identify the primary cancer for most people. Doctors then used this information to select better treatments.

A European study is currently looking at using genetic profiling to select cancer treatments. Researchers want to know if this improves the average amount of time people with CUP live.  


The number of clinical trials looking at treatment for CUP is gradually increasing. Researchers are looking at chemotherapy and targeted cancer drugs (biological therapies). You may have these drugs alone or in combination.

You usually have a combination of chemotherapy drugs for CUP. Doctors can use different combinations, but it usually includes a platinum drug such as cisplatin or carboplatin.

Doctors are currently waiting for the results of a UK trial called CUP-ONE. This study looked at the chemotherapy drugs epirubicin, cisplatin and capecitabine (ECX). As part of the trial, researchers also tested new ways to look for the primary cancer.

Other chemotherapy combinations doctors are looking at around the world include:

  • gemcitabine and oxaliplatin
  • oxaliplatin and capecitabine

In the USA, a small trial compared 2 targeted cancer drugs called bevacizumab and erlotinib with chemotherapy. Doctors found that people who had the targeted treatment lived longer than people who had chemotherapy. 

This led to a second trial that looked at the combination of bevacizumab and erlotinib together with 2 chemotherapy drugs. In this study, people had paclitaxel and carboplatin.

Researchers found that the average amount of time people lived without signs of their disease getting worse was better with this treatment, than with other chemotherapy combinations. They also showed improvements in the average length of time people lived. This was a small study, so doctors would like to continue studying this treatment. 

Other types of targeted cancer drugs doctors are looking at include:

  • everolimus
  • semaxanib
  • trastuzumab
  • pembrolizumab

Living with CUP

A small study looked at the experiences of people affected by CUP. The researchers found that people with CUP have similar issues to people with other cancer types, but to a much greater extent.

Many people with CUP had not heard of this condition before their diagnosis. They found it difficult to get information and felt anxious that the medical team couldn’t agree on the best treatment option.

The researchers also identified a lack of continuity in care. They found that healthcare professionals often disagreed on who was the best specialist to care for each person. This meant that people got referred from one team to another, and were sometimes left feeling caught in the middle.

It also meant they lost contact with specialist nurses when they moved to a different team. This made it more difficult for people and their families to cope.

Researchers think that medical teams need to do more to make sure people don't get moved from one medical team to another. This will help to reduce anxiety.

Last reviewed: 
02 Nov 2017
  • Metastatic malignant disease of unknown primary origin in adults: diagnosis and management

    The National Institute for Health and Care Excellence (NICE), July 2010

  • Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow up

    K. Fizazi and others

    Annals of Oncology, 2015. Vol 26, Supplement 5

  • Adenocarcinoma of unknown primary site

    BMJ Best Practice, 2016

  • Molecular Gene Expression Profiling to Predict the Tissue of Origin and Direct Site-Specific Therapy in Patients With Carcinoma of Unknown Primary Site: A Prospective Trial of the Sarah Cannon Research Institute

    Hainsworth and others

    Journal of Clinical Oncology, 2013. Vol 31, issue 2

  • The information on this page is based on literature searches and specialist checking. We used many references and there are too many to list here. If you need additional references for this information please contact with details of the particular issue you are interested in.