Prognosis and Survival

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.[7-10]

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]

Diagnosis and Patterns of Metastases

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.[7-10]

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 that presents 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. [PubMed: 12957453]
2. McCredie M, Coates M, Churches T, et al.: Cancer incidence in New South Wales, Australia. Eur J Cancer 27 (7): 928-31, 1991. [PubMed: 1834131]
3. Muir C, Weiland L: Upper aerodigestive tract cancers. Cancer 75 (1 Suppl): 147-53, 1995. [PubMed: 8000993]
4. Parkin DM, Whelan SL, Ferlay J, et al., eds.: Cancer Incidence in Five Continents. Volume VII. International Agency for Research on Cancer, 1997.
5. Briasoulis E, Pavlidis N: Cancer of Unknown Primary Origin. Oncologist 2 (3): 142-152, 1997. [PubMed: 10388044]
6. Hainsworth JD, Greco FA: Treatment of patients with cancer of an unknown primary site. N Engl J Med 329 (4): 257-63, 1993. [PubMed: 8316270]
7. Neumann KH, Nystrom JS: Metastatic cancer of unknown origin: nonsquamous cell type. Semin Oncol 9 (4): 427-34, 1982. [PubMed: 7170628]
8. Moertel CG, Reitemeier RJ, Schutt AJ, et al.: Treatment of the patient with adenocarcinoma of unknown origin. Cancer 30 (6): 1469-72, 1972. [PubMed: 4641758]
9. Altman E, Cadman E: An analysis of 1539 patients with cancer of unknown primary site. Cancer 57 (1): 120-4, 1986. [PubMed: 3940611]
10. Ringenberg QS: Tumors of unknown origin. Med Pediatr Oncol 13 (5): 301-6, 1985. [PubMed: 4033541]
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. [PubMed: 8201389]
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. [PubMed: 10589751]

References

1. Haskell CM, Cochran AJ, Barsky SH, et al.: Metastasis of unknown origin. Curr Probl Cancer 12 (1): 5-58, 1988 Jan-Feb. [PubMed: 3067982]
2. Ruddon RW, Norton SE: Use of biological markers in the diagnosis of cancers of unknown primary tumor. Semin Oncol 20 (3): 251-60, 1993. [PubMed: 8503021]
3. Mackay B, Ordonez NG: Pathological evaluation of neoplasms with unknown primary tumor site. Semin Oncol 20 (3): 206-28, 1993. [PubMed: 8503017]
4. Califano J, Westra WH, Koch W, et al.: Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin. J Natl Cancer Inst 91 (7): 599-604, 1999. [PubMed: 10203278]
5. Battifora H: Recent progress in the immunohistochemistry of solid tumors. Semin Diagn Pathol 1 (4): 251-71, 1984. [PubMed: 6400635]
6. Horlings HM, van Laar RK, Kerst JM, et al.: Gene expression profiling to identify the histogenetic origin of metastatic adenocarcinomas of unknown primary. J Clin Oncol 26 (27): 4435-41, 2008. [PubMed: 18802156]
7. Yam LT, Winkler CF, Janckila AJ, et al.: Prostatic cancer presenting as metastatic adenocarcinoma of undetermined origin. Immunodiagnosis by prostatic acid phosphatase. Cancer 51 (2): 283-7, 1983. [PubMed: 6336978]
8. Greco FA, Hainsworth JD: Cancer of unknown primary site. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Lippincott Williams & Wilkins, 2011, pp 2033-51.
9. Motzer RJ, Rodriguez E, Reuter VE, et al.: Molecular and cytogenetic studies in the diagnosis of patients with poorly differentiated carcinomas of unknown primary site. J Clin Oncol 13 (1): 274-82, 1995. [PubMed: 7799031]
10. Feinmesser R, Miyazaki I, Cheung R, et al.: Diagnosis of nasopharyngeal carcinoma by DNA amplification of tissue obtained by fine-needle aspiration. N Engl J Med 326 (1): 17-21, 1992. [PubMed: 1309196]
11. Bosl GJ, Ilson DH, Rodriguez E, et al.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst 86 (5): 349-55, 1994. [PubMed: 8308927]
12. Varadhachary GR, Talantov D, Raber MN, et al.: Molecular profiling of carcinoma of unknown primary and correlation with clinical evaluation. J Clin Oncol 26 (27): 4442-8, 2008. [PubMed: 18802157]
13. Hainsworth JD, Rubin MS, Spigel DR, et al.: Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients with carcinoma of unknown primary site: a prospective trial of the Sarah Cannon research institute. J Clin Oncol 31 (2): 217-23, 2013. [PubMed: 23032625]
14. Hainsworth JD, Johnson DH, Greco FA: Poorly differentiated neuroendocrine carcinoma of unknown primary site. A newly recognized clinicopathologic entity. Ann Intern Med 109 (5): 364-71, 1988. [PubMed: 2841895]
15. Hanna W, Kahn HJ: The ultrastructure of metastatic adenocarcinoma in serous fluids. An aid in identification of the primary site of the neoplasm. Acta Cytol 29 (3): 202-10, 1985 May-Jun. [PubMed: 3859120]
16. Herrera GA, Reimann BE: Electron microscopy in determining origin of metastatic adenocarcinomas. South Med J 77 (12): 1557-66, 1984. [PubMed: 6505766]
17. Mackay B, Ordonez NG: The role of the pathologist in the evaluation of poorly differentiated tumors. Semin Oncol 9 (4): 396-415, 1982. [PubMed: 6763334]

Cervical Lymph Nodes

A histologic diagnosis of metastatic carcinoma in cervical nodes requires a meticulous examination of the upper aerorespiratory tract. Histologically, these tumors are usually squamous cell carcinoma, but occasionally may be adenocarcinoma, melanoma, or anaplastic tumors. Metastatic adenocarcinoma is generally associated with a poor prognosis. Approximately 2% to 5% of patients with primary squamous cell carcinoma of the head and neck region will present with cervical adenopathy as the primary disease manifestation; about 10% of this group will present with bilateral adenopathy. The 3-year survival rate ranges from 35% to 59% when patients with squamous or undifferentiated tumors are treated with radical radiation therapy, surgery, or both.[10-12]

Poorly Differentiated Carcinomas

Investigators have defined a subpopulation of potentially curable patients with 1 or more of the following characteristics:

• Age younger than 50 years.
• Midline tumor distribution, multiple pulmonary nodules or lymph nodes, elevated serum levels of beta human chorionic gonadotropins (HCG) or alpha-fetoprotein (AFP).
• Cells positive for beta HCG or AFP by immunohistochemical stain.
• The presence of neuroendocrine granules.
• Clinical evidence for rapid tumor growth.
• Tumors that were very responsive to chemotherapy or radiation therapy.

In retrospective review, many of these patients, including some complete responders to chemotherapy, did not have any recognizable histopathologic features of germ cell tumors.[13-15] A single study has shown that the i(12p) marker chromosome may be used as a diagnostic tool in patients with suspected midline germ cell tumors.[16]

Metastatic Melanoma to a Single Nodal Site

Approximately 5% of patients with malignant melanoma will present without a documented primary site. Special stains and electron microscopy may be important in establishing the diagnosis. Patients with this diagnosis should, like those with stage II melanoma, have a radical lymph node dissection. Survival is actually slightly better than that seen in patients with stage II melanoma with a documented primary site.[5,17-19] (Refer to the PDQ summary on Melanoma Treatment for more information.)

Isolated Axillary Metastasis

Most patients who present with nodal metastasis above the diaphragm ultimately are documented to have lung cancer, the most common supradiaphragmatic primary malignancy. The presence of isolated axillary metastasis in females, however, raises another possibility. A few studies involving a small number of patients have shown that approximately 50% of patients who present with isolated axillary metastasis of an adenocarcinoma will ultimately be shown to have breast cancer. Although some of these patients will have a positive mammogram after the initial evaluation, approximately 50% of the patients will not. When these patients are treated with local excision, or as having primary breast cancer, 2- to 10-year survival has been obtained in approximately 50% of patients. The availability of estrogen-receptor (ER) and progesterone-receptor (PR) assays may aid in this diagnosis, and these studies should be performed in this setting. If the clinical setting is consistent with breast cancer, and ER and/or PR levels are elevated, CUP with this distribution should be treated as breast cancer.[1,4,20] (Refer to the PDQ summary on Breast Cancer Treatment for more information.)

Inguinal Node Metastasis

Squamous carcinoma detected in the inguinal lymph nodes is almost always metastatic from the genital or anal/rectal area. In females, careful examination of the vulva, vagina, and cervix is indicated, with biopsy of any suspicious areas. The penis of uncircumcised males should be carefully inspected. In both sexes, the anorectal area should be carefully examined, including biopsy of suspicious areas. Isolated metastases present in the central nervous system, the liver, and the genitourinary tract. Information about these presentations may be found in PDQ summaries that specifically detail their management.

In addition to the above situations, significant palliation can be achieved in certain instances in patients with CUP. Breast, prostate, ovarian, and thyroid cancers are all treatable malignancies, even when metastatic, and they represent approximately 15% of all CUP tumors. As with other CUP presentations, the pattern of spread of these malignancies is somewhat atypical. For instance, patients with prostate cancer who present with CUP have an inordinately high incidence of metastases to nonosseous sites such as lung (75%), liver (50%), and brain (25%). Bone metastases are also less common than lung metastases in thyroid cancer presenting as CUP.

References

1. Copeland EM, McBride CM: Axillary metastases from unknown primary sites. Ann Surg 178 (1): 25-7, 1973. [PMC free article: PMC1355857] [PubMed: 4352233]
2. Abbruzzese JL, Abbruzzese MC, Lenzi R, et al.: Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. J Clin Oncol 13 (8): 2094-103, 1995. [PubMed: 7636553]
3. Karsell PR, Sheedy PF, O'Connell MJ: Computed tomography in search of cancer of unknown origin. JAMA 248 (3): 340-3, 1982. [PubMed: 7087129]
4. Patel J, Nemoto T, Rosner D, et al.: Axillary lymph node metastasis from an occult breast cancer. Cancer 47 (12): 2923-7, 1981. [PubMed: 7260879]
5. Klausner JM, Gutman M, Inbar M, et al.: Unknown primary melanoma. J Surg Oncol 24 (2): 129-31, 1983. [PubMed: 6632893]
6. Schapira DV, Jarrett AR: The need to consider survival, outcome, and expense when evaluating and treating patients with unknown primary carcinoma. Arch Intern Med 155 (19): 2050-4, 1995. [PubMed: 7575063]
7. Levine MN, Drummond MF, Labelle RJ: Cost-effectiveness in the diagnosis and treatment of carcinoma of unknown primary origin. CMAJ 133 (10): 977-87, 1985. [PMC free article: PMC1346409] [PubMed: 3933808]
8. Maisey MN, Ellam SV: Investigating the adenocarcinoma of unknown origin (ACUP): a cost benefit analysis. Rev Epidemiol Sante Publique 32 (1): 57-61, 1984. [PubMed: 6718798]
9. Schwartz SC, Klein J, Peters WP: Carcinoma of unknown primary site. In: Stein JH, ed.: Internal Medicine. Mosby, 1998, pp 729-733.
10. DeSanto LW, Neel HB: Squamous cell carcinoma. Metastasis to the neck from an unknown or undiscovered primary. Otolaryngol Clin North Am 18 (3): 505-13, 1985. [PubMed: 2995900]
11. Muraki AS, Mancuso AA, Harnsberger HR: Metastatic cervical adenopathy from tumors of unknown origin: the role of CT. Radiology 152 (3): 749-53, 1984. [PubMed: 6463256]
12. Silverman C, Marks JE: Metastatic cancer of unknown origin: epidermoid and undifferentiated carcinomas. Semin Oncol 9 (4): 435-41, 1982. [PubMed: 7170629]
13. Greco FA, Vaughn WK, Hainsworth JD: Advanced poorly differentiated carcinoma of unknown primary site: recognition of a treatable syndrome. Ann Intern Med 104 (4): 547-53, 1986. [PubMed: 3006571]
14. Hainsworth JD, Wright EP, Gray GF, et al.: Poorly differentiated carcinoma of unknown primary site: correlation of light microscopic findings with response to cisplatin-based combination chemotherapy. J Clin Oncol 5 (8): 1275-80, 1987. [PubMed: 2442318]
15. Hainsworth JD, Johnson DH, Greco FA: Poorly differentiated neuroendocrine carcinoma of unknown primary site. A newly recognized clinicopathologic entity. Ann Intern Med 109 (5): 364-71, 1988. [PubMed: 2841895]
16. Bosl GJ, Ilson DH, Rodriguez E, et al.: Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst 86 (5): 349-55, 1994. [PubMed: 8308927]
17. Panagopoulos E, Murray D: Metastatic malignant melanoma of unknown primary origin: a study of 30 cases. J Surg Oncol 23 (1): 8-10, 1983. [PubMed: 6843134]
18. Reintgen DS, McCarty KS, Woodard B, et al.: Metastatic malignant melanoma with an unknown primary. Surg Gynecol Obstet 156 (3): 335-40, 1983. [PubMed: 6828979]
19. Giuliano AE, Cochran AJ, Morton DL: Melanoma from unknown primary site and amelanotic melanoma. Semin Oncol 9 (4): 442-7, 1982. [PubMed: 7170630]
20. 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. [PubMed: 1617600]

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] Fluorine F 18-fludeoxyglucose 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.[5-7]
• Preoperative radiation therapy followed by radical neck dissection.
• Radical neck dissection.
• Radical neck dissection followed by postoperative radiation therapy to possible sites of origin.[8]

(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%.[9] Carboplatin-containing regimens were found to have equal activity.[10] A paclitaxel-based combination yielded a 48% response rate in 71 patients with various histologic types of carcinoma of unknown origin.[11]

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.[12]

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.[13,14] (Refer to the PDQ summary on Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal 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.[15]
• 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.[16]

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.[17] 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, iodine I 131 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 website.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Righi PD, Sofferman RA: Screening unilateral tonsillectomy in the unknown primary. Laryngoscope 105 (5 Pt 1): 548-50, 1995. [PubMed: 7760677]
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. [PubMed: 10533451]
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. [PubMed: 11822762]
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. [PubMed: 17716824]
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. [PubMed: 18258383]
6. Sher DJ, Balboni TA, Haddad RI, et al.: Efficacy and toxicity of chemoradiotherapy using intensity-modulated radiotherapy for unknown primary of head and neck. Int J Radiat Oncol Biol Phys 80 (5): 1405-11, 2011. [PubMed: 21177045]
7. Villeneuve H, Després P, Fortin B, et al.: Cervical lymph node metastases from unknown primary cancer: a single-institution experience with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 82 (5): 1866-71, 2012. [PubMed: 21497452]
8. 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. [PubMed: 7977958]
9. 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. [PubMed: 1375284]
10. 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. [PubMed: 1450045]
11. Greco FA, Burris HA, Erland JB, et al.: Carcinoma of unknown primary site. Cancer 89 (12): 2655-60, 2000. [PubMed: 11135228]
12. Garrow GC, Greco FA, Hainsworth JD: Poorly differentiated neuroendocrine carcinoma of unknown primary tumor site. Semin Oncol 20 (3): 287-91, 1993. [PubMed: 8503025]
13. 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. [PubMed: 2502058]
14. 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. [PubMed: 2731107]
15. 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. [PubMed: 1617600]
16. 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. [PubMed: 2207996]
17. 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. [PubMed: 3791166]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

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 in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

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PDQ® Adult Treatment Editorial Board. PDQ Carcinoma of Unknown Primary Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/unknown-primary/hp/unknown-primary-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389252]

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