Under healthy conditions, cells grow and multiply in a controlled way. Sometimes a change to the normal DNA that provides instructions on how cells should be built and how they work and behave, can randomly occur, which can be referred to as ‘genomic alteration’. These genomic alterations can cause cells to grow and multiply out of control, eventually forming a cluster of abnormal cells known as cancer cells or a malignant tumour.
The original location of a first tumour is known as the ‘primary site’. A primary cancer cannot always be found because:
In time, cancerous cells can move away from the primary tumour to other places within the body, known as ‘metastases’ or ‘secondary tumours’. The most common places for metastases to be found are the lymph nodes, bone, brain, liver, lung and skin.
Cancer of unknown primary or CUP is the term used when metastases have been found in a person’s body, but the original place where the cancer started is not known at the time of diagnosis. Between 3 and 5 out of every 100 people diagnosed with cancer have CUP. It can affect people of all ages but is most common in people aged 60 years and older.
CUP includes many different types of cancer. Some types are easier to treat than others depending on how fast the metastases are spreading and the organs where they have spread to in the body. CUP are particularly difficult to diagnose and treat. This is because the exact type of cancer is not known and it can be difficult to identify a treatment that will help the patient. At the moment, diagnosis is obtained and guided by an extensive clinical work-up and a pathologist is needed to further identify the features of the tumour under the microscope and testing for molecules in the tumour that help to understand how aggressive the cancer is and what the prognosis might look like. One new method being studied to better diagnose and treat CUP is finding changes in a person’s DNA that may be causing cancer to grow. This method is called ‘genomic profiling’ and is discussed in more detail below.
Sometimes the tests carried out by the doctor will find the primary cancer. When this happens, the cancer is no longer a CUP, and the treatment will follow the usual path for that type of primary cancer.
It is not fully understood what leads to the development of cancer, but there are some things that can increase a person’s chances of getting the disease, called ‘risk factors’. Some risk factors are:
There are many different tests used by doctors to diagnose cancer and to find out if it has spread to other parts of the body. If a doctor thinks that a person has cancer they may be sent for a blood or imaging test. Blood tests measure molecules in the blood that may tell the doctor something is wrong, or may identify tumour cells that have broken off from the original or ‘primary’ tumour and are in the bloodstream. Imaging tests, for example an X-ray, CT scan or MRI scan, give a picture of the inside of a person’s body. These will give the doctor more information about whether they have a tumour, and if so, how big it is and if it has spread.
If a person’s tests show something abnormal, the doctor will talk with them about what to do next. One option could be that the doctor asks for a ‘biopsy’ to collect a small sample of cells from the affected area, so that it can be examined under a microscope or in a laboratory. If the biopsy shows irregular results or confirms that a person has cancer, doctors will sometimes perform a genomic analysis of the tumour to see if changes in the tumour’s DNA could have caused the cancer. This ‘genomic profiling’ can help doctors identify a specific cancer type, and whether the tumour’s genomic profile makes it suitable for a specific, targeted treatment.
The standard treatment for CUP is chemotherapy, but chemotherapy does not work for all patients with CUP. Chemotherapy uses drugs that are toxic to living cells (known as ‘cytotoxic drugs’) that aim to kill cancer cells. Chemotherapy can help to reduce symptoms and improve a person’s quality of life but it will not cure the cancer. Due to its side effects, chemotherapy can also be an additional strain to patients.
In CUP, because the primary cancer site is not known, doctors can find it difficult to choose the best treatment, as the focus is usually on where the metastases have been found. This means that finding the changes in the DNA of the tumour are important to help find out which treatments might work. If genomic changes are found in CUP tumours, these might help your doctor to identify a potential treatment option based on that information.
Potential new treatment options, such as targeted therapies and immunotherapies, are being studied but have not been proved yet.
Potential new treatment options such as targeted therapies or cancer immunotherapy are under investigation. Please ask your doctor or visit ClinicalTrials.gov to find more information about clinical trials for CUP.