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

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The overwhelming majority of patients presenting with carcinoma of unknown primary (CUP) have disseminated disease that is relatively chemoresistant. Potentially curative treatment can be delivered, however, in a few situations.

Cervical Lymph Nodes

All patients should undergo a careful head, neck, and lung evaluation including coronal computed tomography and/or magnetic resonance imaging of the head and neck and directed biopsies of the nasopharynx and tongue base. In those patients with squamous cell or undifferentiated carcinoma, tonsillectomies have been recommended and should be considered if the tonsils have not been previously removed.[1] Fluorodeoxyglucose F 18-positron emission tomography scan may identify an occult primary site in the head and neck area.[2,3] If no primary site can be determined, the following approaches should be considered:

  • Radical radiation therapy with curative intent to the cervical lymph nodes and possible sites of origin.[4] Intensity-modulated radiation therapy (IMRT) may have less short- and long-term toxicity than conventional radiation therapy in terms of xerostomia, acute dysphagia, and skin fibrosis.[5]
  • Preoperative radiation therapy followed by radical neck dissection.
  • Radical neck dissection.
  • Radical neck dissection followed by postoperative radiation therapy to possible sites of origin.[6]

(Refer to the PDQ summary on Metastatic Squamous Neck Cancer with Occult Primary Cancer Treatment for more information.)

Poorly Differentiated Carcinomas

Patients who have poorly differentiated carcinomas with or without serologic or histologic evidence of beta human chorionic gonadotropins or alpha-fetoprotein should be treated with intensive chemotherapy as used in the treatment of disseminated germ cell tumors.

In a series, more than 220 patients with excellent performance status were treated with aggressive combination chemotherapy. This chemotherapy generally consisted of vinblastine, bleomycin, and cisplatin; however, some patients received a doxorubicin-containing modification of this regimen and some received etoposide instead of vinblastine. The response rate was 63%, with a complete response rate of 26%, and a long-term disease-free survival of 16%.[7] Carboplatin-containing regimens were found to have equal activity.[8] A paclitaxel-based combination yielded a 48% response rate in 71 patients with various histologic types of carcinoma of unknown origin.[9]

Poorly Differentiated Neuroendocrine Carcinomas

In a series of 29 patients with poorly differentiated neuroendocrine carcinomas, 19 were treated with intensive cisplatin-based combination chemotherapy, and six additional patients received doxorubicin combinations. Six patients achieved complete response and four of these patients were alive 19 to 100 months after diagnosis.[10]

Peritoneal Carcinomatosis

Women with peritoneal carcinomatosis of an adenocarcinoma serous histologic type have a favorable response to chemotherapy and improved prognosis. Response and survival rates in these patients approach those seen in ovarian cancer patients, and therapy appropriate for ovarian cancer should be used.[11,12] (Refer to the PDQ summary on Ovarian Epithelial Cancer Treatment for more information.)

Isolated Axillary-Nodal Metastasis

The most common primary site for isolated axillary metastasis is the breast. Mammography should be performed in all patients with isolated axillary-nodal metastasis. After an adequate evaluation of the breast and lung to rule out these primary sites, the following treatment options should be considered:

  • Lymph node dissection with or without mastectomy or radiation therapy to the breast with curative intent.[13]
  • Lymph node dissection with or without mastectomy or radiation therapy to the breast with curative intent plus adjuvant chemotherapy with an accepted therapeutic adjuvant approach for breast cancer. This option should be considered especially if breast cancer is proven or if other lymph nodes show adenocarcinoma.[14]

Inguinal Node Metastasis

Metastatic carcinoma in inguinal nodes from an unknown primary source occurs in approximately 1% to 3.5% of patients. A diagnostic excisional-node biopsy should be performed when no primary source of carcinoma can be found. The most common pathologic diagnosis in this instance is Hodgkin lymphoma or non-Hodgkin lymphoma, with CUP being less frequent.

Treatment options:

  • Superficial groin dissection alone.
  • Local excisional biopsy with or without radiation, inguinal node dissection, or chemotherapy.

In a small proportion of patients, local excision alone is sufficient therapy. Initial therapy with radiation may be used successfully in some patients, depending on extent of disease and individual patient characteristics. Isolated metastases also present in the central nervous system, liver, and genitourinary tract.[15] More information can be found in the PDQ summaries for these malignancies.

Melanoma (Melanotic or Amelanotic) Occurring in a Single Nodal Site

Approximately 5% of patients present with no detectable primary site.

Treatment option:

  • Radical lymph node dissection. For patients who present with a single site of nodal metastasis, this treatment will yield a survival that is slightly better than that obtained in conventional stage II melanoma.

Multiple Involvement

When patients present with widespread metastatic disease and special studies reveal a probable primary tumor for which standard systemic therapy is available, such therapy should be administered. This may include hormonal therapy for prostate and breast cancer, I131 for thyroid cancer, or cytotoxic single-agent or combination chemotherapy for hormone-refractory breast and ovarian cancers. Standard approaches for such diseases are available in the specific PDQ summaries for each diagnosis.

The majority of patients will not have a definable primary source. For such patients, a variety of combination chemotherapy approaches have been tried with little success. No treatment can be considered standard at present. Therefore, such patients should be considered for available clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with newly diagnosed carcinoma of unknown primary. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Righi PD, Sofferman RA: Screening unilateral tonsillectomy in the unknown primary. Laryngoscope 105 (5 Pt 1): 548-50, 1995.
  2. Lassen U, Daugaard G, Eigtved A, et al.: 18F-FDG whole body positron emission tomography (PET) in patients with unknown primary tumours (UPT). Eur J Cancer 35 (7): 1076-82, 1999.
  3. Rades D, Kühnel G, Wildfang I, et al.: Localised disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management. Ann Oncol 12 (11): 1605-9, 2001.
  4. Beldì D, Jereczek-Fossa BA, D'Onofrio A, et al.: Role of radiotherapy in the treatment of cervical lymph node metastases from an unknown primary site: retrospective analysis of 113 patients. Int J Radiat Oncol Biol Phys 69 (4): 1051-8, 2007.
  5. Madani I, Vakaet L, Bonte K, et al.: Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer. Int J Radiat Oncol Biol Phys 71 (4): 1158-66, 2008.
  6. Davidson BJ, Spiro RH, Patel S, et al.: Cervical metastases of occult origin: the impact of combined modality therapy. Am J Surg 168 (5): 395-9, 1994.
  7. Hainsworth JD, Johnson DH, Greco FA: Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol 10 (6): 912-22, 1992.
  8. Pavlidis N, Kosmidis P, Skarlos D, et al.: Subsets of tumors responsive to cisplatin or carboplatin combinations in patients with carcinoma of unknown primary site. A Hellenic Cooperative Oncology Group Study. Ann Oncol 3 (8): 631-4, 1992.
  9. Greco FA, Burris HA 3rd, Erland JB, et al.: Carcinoma of unknown primary site. Cancer 89 (12): 2655-60, 2000.
  10. Garrow GC, Greco FA, Hainsworth JD: Poorly differentiated neuroendocrine carcinoma of unknown primary tumor site. Semin Oncol 20 (3): 287-91, 1993.
  11. Strnad CM, Grosh WW, Baxter J, et al.: Peritoneal carcinomatosis of unknown primary site in women. A distinctive subset of adenocarcinoma. Ann Intern Med 111 (3): 213-7, 1989.
  12. Dalrymple JC, Bannatyne P, Russell P, et al.: Extraovarian peritoneal serous papillary carcinoma. A clinicopathologic study of 31 cases. Cancer 64 (1): 110-5, 1989.
  13. Merson M, Andreola S, Galimberti V, et al.: Breast carcinoma presenting as axillary metastases without evidence of a primary tumor. Cancer 70 (2): 504-8, 1992.
  14. Ellerbroek N, Holmes F, Singletary E, et al.: Treatment of patients with isolated axillary nodal metastases from an occult primary carcinoma consistent with breast origin. Cancer 66 (7): 1461-7, 1990.
  15. Guarischi A, Keane TJ, Elhakim T: Metastatic inguinal nodes from an unknown primary neoplasm. A review of 56 cases. Cancer 59 (3): 572-7, 1987.

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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