Treatments by where cancer of unknown primary is found and where it may have started

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To decide how to treat cancer of unknown primary (CUP), the healthcare team first looks at where cancer is found in the body. This can give them an idea of where it started (called the primary site).

Certain lab tests can also help the healthcare team find out where the cancer may have started and the type of CUP it is.

The healthcare team will also consider if you were born with a prostate, testicles or ovaries. This is because certain types of cancer can develop in cells of these organs.

The following are treatment options for the most common types of CUP based on where the cancer is found, where it may have started and the type of cancer it is.

Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan.

Cancer in the lymph nodes under the arm

The type of CUP most often found in the lymph nodes under the arm (called the axillary lymph nodes) is adenocarcinoma.

In people who were assigned female at birth, the primary site of CUP in the lymph nodes under the arm may be the breast. So it is usually treated the same as stage 2 breast cancer. The main treatment is surgery to remove the lymph nodes under the arm (called an axillary lymph node dissection) . You may also be offered one or more of these treatments:

  • surgery to remove the breast (called a mastectomy)
  • radiation therapy to the breast
  • chemotherapy for breast cancer

The healthcare team will also do an HER2 status test and a hormone receptor test on the cancer cells. HER2-positive cancer may also be given targeted therapy for breast cancer. Hormone receptor–positive cancer may be offered hormone therapy for breast cancer. Find out more about treatments for breast cancer.

In people who were assigned male at birth, the primary site of CUP in the lymph nodes under the arm may be the lung. The main treatment is surgery to remove the lymph nodes under the arm. Radiation therapy or chemotherapy may be also be given. Find out more about treatments for non–small cell lung cancer.

Cancer in the lymph nodes in the neck

The type of CUP most often found in the lymph nodes in the neck (called the cervical lymph nodes) is squamous cell carcinoma. The primary site may be the head and neck or the thyroid.

Cancers of the head and neck include oral, nasopharyngeal, oropharyngeal, hypopharyngeal, laryngeal, nasal cavity and paranasal sinus or salivary gland. If the healthcare team thinks that CUP started in one of these organs, you may be offered one of the following treatments:

  • radiation therapy to the lymph nodes in the neck, followed by surgery to remove the lymph nodes (called a neck dissection)
  • neck dissection without radiation therapy
  • radiation therapy alone
  • chemoradiation

If doctors think that the CUP in the lymph nodes in the neck started in the thyroid, you may be offered treatments for thyroid cancer.

Cancer in the lymph nodes in the groin

The type of CUP most often found in the lymph nodes in the groin (called the inguinal lymph nodes) is squamous cell carcinoma. The primary site may be the genitals, anus or rectum.

The main treatment is surgery to remove lymph nodes in the groin (called an inguinal lymph node dissection) .

If cancer is found in more than one lymph node in the groin, you may be offered radiation therapy or sometimes chemoradiation.

Cancer in the abdominal cavity of people who were born with ovaries

The type of CUP most often found in the abdominal cavity of people who were born with ovaries is adenocarcinoma. The primary site may be the ovaries.

CUP in the lining of the abdomen in a person who was born with ovaries is usually treated the same as stage 3 epithelial ovarian cancer. Treatments may include:

  • surgery to remove as much of the cancer as possible (called debulking surgery)
  • chemotherapy

Find out more about treatments for ovarian cancer.

The healthcare team may check the amount of the tumour marker cancer antigen 125 (CA125) in the blood. This will tell them how well treatment is working. Find out more about cancer antigen 125 (CA125).

Cancer in the bones of people with a high PSA level

The type of CUP most often found in the bones of people who also have a high prostate-specific antigen (PSA) level in the blood is adenocarcinoma. The primary site may be the prostate.

CUP in the bones of people with a high PSA level is usually treated the same as advanced prostate cancer. Treatments may include hormone therapy with or without radiation therapy.

Find out more about treatments for prostate cancer.

Cancer in the chest

The type of CUP most often found in the chest is adenocarcinoma. The primary site may be the lung when CUP is found in the lungs, in the space between the lungs (called the mediastinum) or in the lymph nodes in the chest.

CUP in the chest is usually treated the same as later stage non–small cell lung cancer. You may be offered one of the following treatments:

  • surgery if the cancer can be completely removed
  • radiation therapy with or without surgery

Find out more about treatments for non–small cell lung cancer.

Cancer in the liver and abdomen

The type of CUP that is most often found in the liver and the abdomen is adenocarcinoma. The primary site may be the colon.

CUP found in the liver and the abdomen is usually treated the same as stage 4 colon cancer. You may be offered one or more of the following treatments:

  • chemotherapy
  • targeted therapy
  • immunotherapy
  • surgery

Find out more about treatments for colon cancer.

Clinical trials

Talk to your doctor about clinical trials open to people with CUP in Canada. Clinical trials look at new ways to prevent, find and treat cancer. Find out more about clinical trials.

If you can’t have or don’t want cancer treatment

You may want to consider a type of care to make you feel better without treating the cancer itself. This may be because the cancer treatments don't work anymore, they're not likely to improve your condition or they may cause side effects that are hard to cope with. There may also be other reasons why you can't have or don't want cancer treatment.

Talk to your healthcare team. They can help you choose care and treatment for advanced cancer.

Expert review and references

  • Tien Le, MD, FRCSC, DABOG
  • American Cancer Society. Treating a Cancer of Unknown Primary. 2018. https://www.cancer.org/.
  • American Society of Clinical Oncology (ASCO). Cancer.net: Unknown Primary: Types of Treatment. 2021.
  • Fizazi K, Greco FA, Pavlidis N, Daugaard G, Oien K, Pentheroudakis G. Cancers of unknown primary site: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2015: 26(Supplement 5):v133–v138.
  • PDQ Adult Treatment Editorial Board. Carcinoma of Unknown Primary Treatment (PDQ®) – Health Professional Version. Bethesda, MD: National Cancer Institute; 2018. https://www.cancer.gov/.
  • PDQ Adult Treatment Editorial Board. Carcinoma of Unknown Primary Treatment (PDQ®) – Patient Version. Bethesda, MD: National Cancer Institute; 2021. https://www.cancer.gov/.
  • National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Occult Primary (Cancer of Unknown Primary) Version 1.2023. 2022.
  • Yentz S, Bhave M, Cobain E, Baker L. Cancer of Unknown Primary. DeVita VT Jr., Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology. 11th ed. Philadelphia, PA: Wolters Kluwer; 2019: Kindle version, ch 108, https://read.amazon.ca/?asin=B0777JYQQC&language=en-CA.
  • Tan WW. Medscape Reference: Metastatic Cancer With Unknown Primary Site. 2022. https://www.medscape.com/oncology.

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