Definition and Overview

Cancer is a disease that occurs due to the uncontrolled division of abnormal cells. It can develop in different parts of the body and is identified based on its location (e.g., cancer in breast tissue is referred to as breast cancer). Cancer cells can spread (metastasise) to different organs of the body if they break away from the malignant tumour and travel through the lymph system or bloodstream. Metastatic cancer has the same name as primary cancer. For example, lung cancer that has spread to the brain is still referred to as lung cancer and not brain cancer.

In very rare cases, doctors are unable to identify the origin of metastatic cancer and the condition is referred to as malignant tumour of unknown origin, metastatic cancer of unknown primary, or cancer of the unknown primary (CUP).

CUP is an advanced stage of cancer that is difficult to control. Available treatment methods are usually used to slow the growth of cancer, provide symptoms relief, and prolong patients' lives. Cancer of unknown primary prognosis is generally not good and depends on many factors such as the extent of cancer spread, the type of cancer cells and their location, the patient’s general health condition, methods used to treat the condition, and how well cancer responds to treatment.

On average, cancer of unknown primary life expectancy is about 12 months following diagnosis. However, a number of CUPs have better survival rates. These include cancer that has spread throughout the pelvic cavity. If treated the same way as advanced ovarian cancer, patients have 34% five-year cancer of unknown primary survival rate.

Causes of Condition

Cancer cells can spread locally (invade nearby tissue), regionally (spread to nearby organs and lymph nodes), or to distant organs and structures where they form new tumours. Although the disease can spread to any part of the body, different types of cancer have common metastatic sites.

  • Bladder and thyroid cancers commonly spread to the lung, bone, and liver

  • Breast cancer commonly spreads to the lung, liver, bone, and brain

  • Colon, pancreatic, rectal, stomach, and ovarian cancers commonly spread to the peritoneum, lung, and liver

  • Kidney and prostate cancers commonly spread to the adrenal gland, lung, brain, bone, and liver

  • Lung cancer commonly spreads to the liver, brain, bone, and adrenal glands

  • Melanoma commonly spreads to the muscle, skin, lung, brain, and bone

  • Uterine cancer commonly spreads to the vagina, peritoneum, lung, liver, and bone

Doctors use this information when trying to identify the primary site of tumour. This is important as CUPs are treated the same way as the primary cancer.

Key Symptoms

Cancer of unknown primary origin produces wide-ranging symptoms depending on the site of metastasis and the extent of the disease.

  • Bone pain and fractures, when cancer affects any part of the musculoskeletal system

  • Dizziness, headaches, and seizures, when cancer spreads to the brain

  • Breathing problems, when the lungs are affected

  • Abdominal swelling, if cancer spreads to abdominal organs

  • Jaundice, if cancer spreads to the liver

In some cases, the symptoms of metastatic cancer are the only ones noticed by patients prompting them to seek medical attention. For example, those with prostate cancer normally do not experience any symptoms. However, if cancer spreads to the bone, patients may experience bone pain.

Who to See and Types of Treatments Available

Patients with cancer of an unknown primary are treated by a multidisciplinary team of doctors composed of cancer specialists (oncologists) and surgeons, among others. They exhaust all available options to identify the primary site of cancer in order to effectively plan the best course of treatment. They perform a thorough physical exam as well as review the patient’s medical history. Patients then undergo a series of diagnostic tests, including urinalysis, blood chemistry studies, complete blood count, and fecal occult blood test.

A very useful diagnostic test is biopsy in which a small amount of tissue sample is obtained from the malignant tumour and closely analysed under a microscope. Cells from different parts of the body have unique characteristics. For example, cancer tissue from the breast is made up of breast cells. If the tissue sample obtained from a breast tumour contains cells other than breast cells, it means that it is a metastatic cancer.

Unfortunately, in some cases, the primary cancer site is never found despite the number of diagnostic procedures and imaging tests performed. When this happens, cancer of unknown primary treatment is based on the available information such as the tumour’s location and the patient’s overall health condition.

The standard treatment for cancer of unknown primary site is surgery, which goal is to remove the tumour along with a wide margin of tissue surrounding it. This is followed by adjuvant therapies that kill any cancer cells left or keep the tumour from growing. These therapies include:

  • Radiation therapy – Uses radiation or high-energy x-rays to kill cancer cells or prevent them from progressing. There are two types of radiation therapy; external radiation therapy that sends radiation to the tumour from outside the body and internal radiation therapy that involves placing radioactive substances near or directly into the cancer.

  • Chemotherapy – Just like radiation therapy, chemotherapy also aims to kill cancer cells or keep them from growing. It uses drugs that can be taken orally or injected into a vein or muscle.

  • Hormone therapy – Removes specific types of hormones that can cause certain cancers to grow.

In some cases, a malignant tumour of unknown origin can no longer be controlled, especially if it has already invaded various organs. In such events, doctors discuss end-of-life care that aims to control patient’s symptoms and side effects of their treatment.

New types of therapies are constantly being explored to improve cancer treatment outcomes. These include identifying techniques on how to boost the immune system to fight cancer as well as exploring new ways to disrupt the process in which normal cells become cancerous.


  • Merson M, Andreola S, Galimberti V, et al. Breast carcinoma presenting as axillary metastases without evidence of a primary tumor. Cancer. 1992 Jul 15. 70(2):504-8.

  • Davidson BJ, Spiro RH, Patel S, et al. Cervical metastases of occult origin: the impact of combined modality therapy. Am J Surg. 1994 Nov. 168(5):395-9.

  • [Guideline] Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G, et al. Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep. 26 Suppl 5:v133-8.

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