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

CUP is the twelth most common cancer in men and the tenth most common in women1. It is the fifth most common cause of cancer death, causing around 5% of cancer deaths.

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.

See our understanding cancer of unknown primary booklet.

Screening

There is no screening method for CUP. 

Symptoms and diagnosis

Some people with metastatic cancer have no symptoms, but common symptoms 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, feeling extremely tired.

Tests are ordered to ensure that cancers which are still curable or treatable, even when spread, are not missed. Tests may include a biopsy, physical examination, x-ray and blood test. Further diagnostic tests are done, based on the site of the secondary cancer/s and any ‘clues’ as to where the cancer may have started.

Diagnostic tools include blood biochemistry (checking for markers for cancers such as breast or prostate that could be treated with hormones), faecal occult blood testing, urinalysis, histopathogical review of all biopsy material using immunohistochemistry, CT of the abdomen and pelvis, mammography and PET scan.

Staging

Staging systems differ for different cancer types. For most cancers there are four stages, with stage 1 being an early cancer and stage 4 an advanced cancer. Because a CUP has already spread, it must be stage 2 or higher. If it has spread to another body organ, it is a stage 4 cancer.

Causes

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 CUP patients have a history of smoking. Other risk factors may include older age, diet, alcohol and obesity – common risk factors for many cancers.

Prevention

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.

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.  

Prognosis

For most individuals diagnosed with cancer prognosis depends on the type and stage of cancer, as well as their age and general health at the time of diagnosis. CUP is not diagnosed until a patient has metastatic cancer, and treatment is difficult because the primary cancer type can not be determined. Five year survival for people diagnosed with CUP is 16%.

1) Excluding non-melanoma skin cancer, which is the most commonly diagnosed cancer according to general practice and hospitals data, however there is no reporting of cases to cancer registries.