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What is cancer of unknown primary?

Cancer of unknown primary (CUP) is the term used to describe a metastatic cancer (cancer that has spread) with an unknown starting point.

Usually, when cancer spreads, the secondary cancer cells look like abnormal versions of the primary cancer cells (in the tissue where the cancer began). For example, if breast cancer spreads to the lungs, the metastatic tumour in the lung is made up of cancerous breast cells (not lung cells) and is then described as metastatic breast cancer (not lung cancer).

If it is not possible to identify the type of cancer cells the diagnosis is CUP.

It is estimated that more than 2,600 people were diagnosed with a cancer of unknown primary site in 2023. The average age at diagnosis is 76 years old.



Cancer of unknown primary signs and symptoms

Some people with metastatic cancer have no symptoms, but common symptoms may include: 

  • breathlessness or discomfort in the chest

  • bone pain, back pain

  • swelling and discomfort in the abdomen, fluid collecting in the abdomen (ascites), yellowing of the skin and eyes (jaundice)

  • swollen lymph glands such as those in the neck, underarm, chest or groin

  • general symptoms such as weight loss, headaches, no appetite and feeling extremely tired.



Causes of cancer of unknown primary

For patients with CUP, the primary cancer site is not known, therefore it is difficult to identify risk factors. Smoking may be an important risk factor, as more than half of cancer of unknown primary patients have a history of smoking. Other risk factors may include older age, diet, alcohol and obesity - common risk factors for many cancers. 



    Diagnosis of cancer of unknown primary

    CUP is not diagnosed until a patient has metastatic cancer, and treatment is difficult because the primary cancer type cannot be determined. 

    Tests are ordered to ensure that cancers which are still curable or treatable, even when spread, are not missed. 

    Tests are done based on the site of the secondary cancer/s and any "clues" as to where the cancer may have started. The following tests may be used.  

    Blood tests

    These will examine the number and type of blood cells and measure the levels of certain blood chemicals (tumour markers). 

    Urine tests

    Urine can be tested for any abnormal cells or to see if there are any problems with organs such as the kidneys or bladder. 

    Biopsy

    Samples of tissue from a secondary tumour or an enlarged lymph gland are removed for examination under a microscope. 

    Endoscopy

    A procedure that uses an instrument called an endoscope to look inside the body and remove small tissue samples. 

    Imaging tests

    X-rays, ultrasounds and CT of the abdomen and pelvis, mammography, MRI and PET scans create pictures of the inside of the body. 

    Other tests

    A histopathogical review of all biopsy material using immunohistochemistry may also be undertaken. 

    If these tests find where the cancer started, the cancer is no longer an unknown primary and is treated according to the tissue of origin. 

    After a diagnosis of cancer of unknown primary  

    After being diagnosed with cancer of unknown primary, you may feel shocked, upset, anxious or confused. These are normal responses. A diagnosis of cancer of unknown primary affects each person differently. For most it will be a difficult time, however some people manage to continue with their normal daily activities. 

    You may find it helpful to talk about your treatment options with your doctors, family and friends. Ask questions and seek as much information as you feel you need. It is up to you as to how involved you want to be in making decisions about your treatment. 

    Find out more about best cancer of unknown primary care:



    Treatment for cancer of unknown primary

    Staging

    Staging differs for different cancer types. For most cancers there are four stages, with stage I being an early cancer and stage IV an advanced cancer. 

    Staging is a way to describe the spread of cancer. However, CUP cannot be given a stage because the primary cancer is not known and the cancer has already spread to other parts of the body when it is found.

    Types of treatment

    For most cancers, treatment is determined by the type of cancer and depends on correct diagnosis and staging. Because the primary cancer is unknown, there is no standard treatment for CUP. 

    The main treatment used for CUP is broad spectrum chemotherapy, unless the unknown primary is in a very specific area. For example, neck nodes are usually treated like head and neck cancer, axillary node presentations are treated in the same manner as breast cancers, and peritoneal presentations are treated like ovarian cancer. 

    Palliative care

    In some cases of CUP, your medical team may talk to you about palliative care. Palliative care aims to improve your quality of life by alleviating symptoms of cancer. 

    As well as slowing the spread of CUP, palliative treatment can relieve pain and help manage other symptoms. Treatment may include radiotherapy, chemotherapy or other drug therapies.

    Treatment Team

    Depending on your treatment, your treatment team may consist of a number of different health professionals, such as:
    • GP (General Practitioner) - looks after your general health and works with your specialists to coordinate treatment.
    • Surgeon- surgically removes tumours and performs some biopsies.
    • Gastroenterologist - specialises in diseases of the digestive system.
    • Urologist- specialises in the treatment of diseases of the urinary system (male and female) and the male reproductive system
    • Respiratory physician- investigates symptoms, is involved in diagnosis and determines initial treatment options.
    • Haematologist- specialises in diagnosing and treating diseases of the blood and lymphatic system.
    • Radiologist- interprets diagnostic scans (including CT, MRI and PET scans).
    • Radiation oncologist - prescribes and coordinates radiation therapy treatment.
    • Radiation therapist- plans and delivers radiation therapy.
    • Medical oncologist - prescribes and coordinates the course of chemotherapy.
    • Cancer care coordinators- coordinate your care, liaise with the multidisciplinary team and support you and your family throughout treatment.
    • Palliative care team- assist with control of symptoms and help maintain quality of life as well as offering a range of support services.
    • Other allied health professionals - such as social workers, pharmacists, and counsellors.


    Screening for cancer of unknown primary

    There is currently no national screening program for CUP available in Australia. 



    Preventing cancer of unknown primary

    Since the causes of CUP are unknown, there is no prevention advice specific to this disease. Having a generally healthy lifestyle - including not smoking, maintaining a healthy diet and weight and limiting alcohol consumption - may be protective. 



    Prognosis for cancer of unknown primary

    It is not possible for a doctor to predict the exact course of a disease, as it will depend on each person's individual circumstances. However, your doctor may give you a prognosis - the likely outcome of the disease - based on the test results, the rate of tumour growth, as well as your age, fitness and medical history. 

    Although most cancers of unknown primary can't be cured, treatment can keep some cancers of unknown primary under control for months or years. 



    Sources

    • Understanding Cancer of Unknown Primary, Cancer Council Australia, ©2020. Last medical review of source booklet: June 2020. 
    • Australian Institute of Health and Welfare. Cancer data in Australia [Internet]. Canberra: Australian Institute of Health and Welfare, 2023 [cited 2023 Sept 04]. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia

    This information was last updated September 2023.

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