Cancer of unknown primary origin natural history, complications and prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Early clinical features include fatigue, weight-loss, and loss of appetite.

Common complications of cancer of unknown primary origin, may include: hypercalcemia, adrenal insufficiency, and inappropriate antidiuretic syndrome, hematologic disorders, and malignant effusions.

Prognosis is generally poor, and the average survival time of patients with cancer of unknown primary origin is approximately 6-12 months after diagnosis.

Natural History, Complications, and Prognosis

Natural History

Cancer of unknown primary presents differently depending on the organs affected by the metastatic spread of the tumor; however, there are certain common characteristics that patients with CUP present with:^[1]

Brief medical history without specific complaints
Advanced metastases at time of diagnosis
Irregular pattern of metastatic spread
Usually with poor prognosis

Upon presentation, around 60% of patients with cancer of unknown primary have two or more affected sites.^[2]

The most common sites of metastasis in cancer of unknown origin are lymph nodes, lungs, liver, bones, and pleura.^[3]

Complications

If left untreated, the majority of patients with cancer of unknown primary origin may progress to develop multiple organ failure, heart failure, and death.

Common complications of cancer of unknown primary origin, may include: hypercalcemia, adrenal insufficiency, and inappropriate antidiuretic syndrome, hematologic disorders, and malignant effusions.^[2]

Prognosis

Prognosis is generally poor, and the average survival time of patients with cancer of unknown primary origin is approximately 6-12 months after diagnosis.^[4]^[5]

Sites of metastasis and prognosis differ with the types of CUPs:^[6]^[7]^[8]^[9]

Type	Common sites of metastasis	Characteristics	5-year survival rates
Adenocarcinoma	Liver, lungs, bones, axillary lymph nodes, and peritnoneum	Most common type of CUP	5%
Squamous cell carcinoma	Cervical lymph nodes	More common in males	30%
Neuroendocrine carcinoma	Bone marrow, bone lesions, lymph nodes, and lungs	Predominating type in children	17%
Undifferntiated	Lungs and lymph nodes	Rapid tumor growth	13-16%

References

↑ Löffler H, Neben K, Krämer A (2014). “[Cancer of unknown primary. Epidemiology and pathogenesis]”. Radiologe. 54 (2): 107–11. doi:10.1007/s00117-013-2544-z. PMID 24435156.
↑ ^2.0 ^2.1 Abbruzzese JL, Abbruzzese MC, Hess KR, Raber MN, Lenzi R, Frost P (1994). “Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients”. J Clin Oncol. 12 (6): 1272–80. doi:10.1200/JCO.1994.12.6.1272. PMID 8201389.
↑ Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M; et al. (1988). “Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients”. Arch Intern Med. 148 (9): 2035–9. PMID 3046543.
↑ Nelson KA, Walsh D, Abdullah O, McDonnell F, Homsi J, Komurcu S, LeGrand SB, Zhukovsky DS (2000). “Common complications of advanced cancer”. Semin. Oncol. 27 (1): 34–44. PMID 10697020.
↑ Altman E, Cadman E (1986). “An analysis of 1539 patients with cancer of unknown primary site”. Cancer. 57 (1): 120–4. PMID 3940611.
↑ Invalid <ref> tag; no text was provided for refs named pmid10653878
↑ Hainsworth JD, Dial TW, Greco FA (1988). “Curative combination chemotherapy for patients with advanced poorly differentiated carcinoma of unknown primary site”. Am J Clin Oncol. 11 (2): 138–45. PMID 2451881.
↑ Nguyen C, Shenouda G, Black MJ, Vuong T, Donath D, Yassa M (1994). “Metastatic squamous cell carcinoma to cervical lymph nodes from unknown primary mucosal sites”. Head Neck. 16 (1): 58–63. PMID 8125789.
↑ Kuttesch JF, Parham DM, Kaste SC, Rao BN, Douglass EC, Pratt CB (1995). “Embryonal malignancies of unknown primary origin in children”. Cancer. 75 (1): 115–21. PMID 7804965.

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[pmid24435156-1] Löffler H, Neben K, Krämer A (2014). “[Cancer of unknown primary. Epidemiology and pathogenesis]”. Radiologe. 54 (2): 107–11. doi:10.1007/s00117-013-2544-z. PMID 24435156.

[pmid8201389-2] 2.0 ^2.1 Abbruzzese JL, Abbruzzese MC, Hess KR, Raber MN, Lenzi R, Frost P (1994). “Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients”. J Clin Oncol. 12 (6): 1272–80. doi:10.1200/JCO.1994.12.6.1272. PMID 8201389.

[pmid3046543-3] Le Chevalier T, Cvitkovic E, Caille P, Harvey J, Contesso G, Spielmann M; et al. (1988). “Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients”. Arch Intern Med. 148 (9): 2035–9. PMID 3046543.

[pmid10697020-4] Nelson KA, Walsh D, Abdullah O, McDonnell F, Homsi J, Komurcu S, LeGrand SB, Zhukovsky DS (2000). “Common complications of advanced cancer”. Semin. Oncol. 27 (1): 34–44. PMID 10697020.

[pmid3940611-5] Altman E, Cadman E (1986). “An analysis of 1539 patients with cancer of unknown primary site”. Cancer. 57 (1): 120–4. PMID 3940611.

[pmid10653878-6] Invalid <ref> tag; no text was provided for refs named pmid10653878

[pmid2451881-7] Hainsworth JD, Dial TW, Greco FA (1988). “Curative combination chemotherapy for patients with advanced poorly differentiated carcinoma of unknown primary site”. Am J Clin Oncol. 11 (2): 138–45. PMID 2451881.

[pmid8125789-8] Nguyen C, Shenouda G, Black MJ, Vuong T, Donath D, Yassa M (1994). “Metastatic squamous cell carcinoma to cervical lymph nodes from unknown primary mucosal sites”. Head Neck. 16 (1): 58–63. PMID 8125789.

[pmid7804965-9] Kuttesch JF, Parham DM, Kaste SC, Rao BN, Douglass EC, Pratt CB (1995). “Embryonal malignancies of unknown primary origin in children”. Cancer. 75 (1): 115–21. PMID 7804965.

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