Carcinoma of Unknown Primary Treatment (PDQ®): Treatment - Health Professional Information [NCI]

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The site of origin of a histologically documented carcinoma is not identified clinically in approximately 3% of patients; this situation is often referred to as carcinoma of unknown primary (CUP) origin or occult primary malignancy.[1,2,3,4,5,6]

The definition of a CUP varies from study to study; however, at a minimum, this determination should include a biopsy of the tumor and a thorough history and complete physical examination that includes head and neck, rectal, pelvic, and breast examinations; chest x-rays; a complete blood cell count; urinalysis; and an examination of the stool for occult blood. The value of other radiographic tests will be discussed in the stage information section. When these results do not reveal signs of a potential primary lesion and the biopsy is not consistent with a primary tumor at the biopsy site, a CUP must be assumed. The majority of CUP are adenocarcinomas or undifferentiated tumors; less commonly, squamous cell carcinoma, melanoma, sarcoma, and neuroendocrine tumors can also present with a primary site of origin that cannot be determined. In approximately 15% to 25% of patients, the primary site cannot be identified even at postmortem examination.[7]

The prognosis for patients with CUP is poor. As a group, the median survival is approximately 3 to 4 months with less than 25% and 10% of patients alive at 1 and 5 years, respectively. CUP is represented by a heterogeneous group of diseases all of which have presented with metastasis as the primary manifestation. Although the majority of diseases are relatively refractory to systemic treatments, certain clinical presentations of CUP carry a much better prognosis. In each instance, distinct clinical and pathologic details require consideration for appropriate, potentially curative, management.[7,8,9,10]

A retrospective review of 657 consecutive patients with CUP (270 additional patients were excluded as a result of identification of a primary malignancy, a noncarcinoma cell type, or no malignancy) reported several variables of significant prognostic importance identified by multivariate analysis.[11] Lymph node involvement and neuroendocrine histology were associated with longer survival; male sex, increasing number of involved organ sites, adenocarcinoma histology, and hepatic involvement were unfavorable prognostic factors. Adrenal involvement has also been noted to be a poor prognostic finding.[12]

Conceptually, CUP represents a tumor that has a greater propensity for early dissemination than the more common presentation in which the primary tumor is apparent with or without metastasis.

The distribution of primary sites that are likely to result in CUP contrasts with the distribution of major primary adenocarcinomas as reported in the Surveillance, Epidemiology, and End Results data. Most large studies have shown that carcinoma of the lung and pancreas are the most common primary carcinomas that initially present as CUP. Other common malignancies such as colorectal, breast, and prostate cancers infrequently present as CUP.[7,8,9,10]

The pattern of spread of CUP at diagnosis can provide clues to the likelihood of the primary site being above or below the diaphragm. Lung metastases are twice as common in primary sites ultimately found to be above the diaphragm. Liver metastases are more common from primary disease below the diaphragm. The pattern of metastasis from a carcinoma presenting as CUP may be significantly different from that which would be expected from the usual presentation. For instance, bone metastases are approximately three times more common in pancreatic cancer presenting as CUP, while osseous metastasis from lung cancer is about 10 times less common when it presents as CUP compared with the usual presentation. The biologic bases for these differences in presentation, incidence, and pattern of metastases are unknown.[7]

Although only a minority of patients will have curable disease or a disease for which there is substantial palliative benefit, the appropriate use of special diagnostic pathology and selected radiologic studies will identify patients for whom directed therapy will provide the best possible chance for response.

References:

  1. Pavlidis N, Briasoulis E, Hainsworth J, et al.: Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer 39 (14): 1990-2005, 2003.
  2. McCredie M, Coates M, Churches T, et al.: Cancer incidence in New South Wales, Australia. Eur J Cancer 27 (7): 928-31, 1991.
  3. Muir C, Weiland L: Upper aerodigestive tract cancers. Cancer 75 (1 Suppl): 147-53, 1995.
  4. Parkin DM, Whelan SL, Ferlay J, et al., eds.: Cancer Incidence in Five Continents. Volume VII. Lyon, France: International Agency for Research on Cancer, 1997.
  5. Briasoulis E, Pavlidis N: Cancer of Unknown Primary Origin. Oncologist 2 (3): 142-152, 1997.
  6. Hainsworth JD, Greco FA: Treatment of patients with cancer of an unknown primary site. N Engl J Med 329 (4): 257-63, 1993.
  7. Neumann KH, Nystrom JS: Metastatic cancer of unknown origin: nonsquamous cell type. Semin Oncol 9 (4): 427-34, 1982.
  8. Moertel CG, Reitemeier RJ, Schutt AJ, et al.: Treatment of the patient with adenocarcinoma of unknown origin. Cancer 30 (6): 1469-72, 1972.
  9. Altman E, Cadman E: An analysis of 1539 patients with cancer of unknown primary site. Cancer 57 (1): 120-4, 1986.
  10. Ringenberg QS: Tumors of unknown origin. Med Pediatr Oncol 13 (5): 301-6, 1985.
  11. Abbruzzese JL, Abbruzzese MC, Hess KR, et al.: Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol 12 (6): 1272-80, 1994.
  12. Hess KR, Abbruzzese MC, Lenzi R, et al.: Classification and regression tree analysis of 1000 consecutive patients with unknown primary carcinoma. Clin Cancer Res 5 (11): 3403-10, 1999.

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of carcinoma of unknown primary. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board. Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewer for Carcinoma of Unknown Primary Treatment is:

  • James P. Neifeld, MD (Medical College of Virginia Hospital & Virginia Commonwealth University)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."

The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Carcinoma of Unknown Primary Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/unknownprimary/HealthProfessional. Accessed <MM/DD/YYYY>.

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.

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More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site's Contact Form.

Last Revised: 2011-02-23

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