Metastases in the Absence of a Primary Tumor: Advances in the Diagnosis and Treatment of CUP Syndrome

Overview

Journal Dtsch Arztebl Int

Specialties General Medicine
Public Health

Date 2009 Jul 23

PMID 19623297

Citations 15

Authors

Kai Neben

Gerdt Hubner

Gunnar Folprecht

Dirk Jager

Alwin Kramer

Affiliations

Soon will be listed here.

Abstract

Introduction: The term cancer of unknown primary site (CUP) syndrome is used to describe malignancies in which a complete diagnostic work-up detects metastases in the absence of an identifiable primary tumor.

Methods: Based on a selective literature review, national and international guidelines, and the experience of the "Arbeitskreis CUP-Syndrom der Arbeitsgemeinschaft Internistische Onkologie der Deutschen Krebsgesellschaft" (CUP Syndrome Committee of the Medical Oncology Joint Working Group of the German Cancer Society), developments in the diagnosis and treatment of CUP syndrome are reported.

Results: Most patients diagnosed with CUP have an unfavorable prognosis, with a life expectancy of less than 12 months. Nevertheless, it is important to identify subsets of patients in whom specific treatment offers the chance of long-term survival or even full recovery.

Discussion: Only rigorous further development of diagnostic tools and treatment protocols will enable an improvement of the poor prognosis of patients with CUP syndrome. Specific molecular treatment strategies have shown promising results.

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References

Greco F, Burris 3rd H, Litchy S, Barton J, Bradof J, Richards P . Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol. 2002; 20(6):1651-6. DOI: 10.1200/JCO.2002.20.6.1651. View

Hainsworth J, Spigel D, Litchy S, Greco F . Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study. J Clin Oncol. 2006; 24(22):3548-54. DOI: 10.1200/JCO.2005.05.0575. View

Massard C, Voigt J, Laplanche A, Culine S, Lortholary A, Bugat R . Carcinoma of an unknown primary: are EGF receptor, Her-2/neu, and c-Kit tyrosine kinases potential targets for therapy?. Br J Cancer. 2007; 97(7):857-61. PMC: 2360401. DOI: 10.1038/sj.bjc.6603942. View

Levi F, Te V, Erler G, Randimbison L, La Vecchia C . Epidemiology of unknown primary tumours. Eur J Cancer. 2002; 38(13):1810-2. DOI: 10.1016/s0959-8049(02)00135-1. View

Culine S, Fabbro M, Ychou M, Romieu G, Cupissol D, Pujol H . Chemotherapy in carcinomas of unknown primary site: a high-dose intensity policy. Ann Oncol. 1999; 10(5):569-75. DOI: 10.1023/a:1026478009050. View

Hainsworth J, Lennington W, Greco F . Overexpression of Her-2 in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site. J Clin Oncol. 2000; 18(3):632-5. DOI: 10.1200/JCO.2000.18.3.632. View

Eagan R, Therneau T, Rubin J, Long H, SCHUTT A . Lack of value for cisplatin added to mitomycin-doxorubicin combination chemotherapy for carcinoma of unknown primary site. A randomized trial. Am J Clin Oncol. 1987; 10(1):82-5. DOI: 10.1097/00000421-198702000-00018. View

Greco F, Rodriguez G, Shaffer D, Hermann R, Litchy S, Yardley D . Carcinoma of unknown primary site: sequential treatment with paclitaxel/carboplatin/etoposide and gemcitabine/irinotecan: a Minnie Pearl Cancer Research Network phase II trial. Oncologist. 2004; 9(6):644-52. DOI: 10.1634/theoncologist.9-6-644. View

Gutzeit A, Antoch G, Kuhl H, Egelhof T, Fischer M, Hauth E . Unknown primary tumors: detection with dual-modality PET/CT--initial experience. Radiology. 2004; 234(1):227-34. DOI: 10.1148/radiol.2341031554. View

10.

Huebner G, Link H, Kohne C, Stahl M, Kretzschmar A, Steinbach S . Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial. Br J Cancer. 2008; 100(1):44-9. PMC: 2634671. DOI: 10.1038/sj.bjc.6604818. View

11.

Rosenfeld N, Aharonov R, Meiri E, Rosenwald S, Spector Y, Zepeniuk M . MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol. 2008; 26(4):462-9. DOI: 10.1038/nbt1392. View

12.

Nanni C, Rubello D, Castellucci P, Farsad M, Franchi R, Toso S . Role of 18F-FDG PET-CT imaging for the detection of an unknown primary tumour: preliminary results in 21 patients. Eur J Nucl Med Mol Imaging. 2005; 32(5):589-92. DOI: 10.1007/s00259-004-1734-3. View

13.

Pelosi E, Pennone M, Deandreis D, Douroukas A, Mancini M, Bisi G . Role of whole body positron emission tomography/computed tomography scan with 18F-fluorodeoxyglucose in patients with biopsy proven tumor metastases from unknown primary site. Q J Nucl Med Mol Imaging. 2006; 50(1):15-22. View

14.

Bridgewater J, van Laar R, Floore A, Veer L . Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary. Br J Cancer. 2008; 98(8):1425-30. PMC: 2361712. DOI: 10.1038/sj.bjc.6604315. View

15.

Hedley D, Leary J, Kirsten F . Metastatic adenocarcinoma of unknown primary site: abnormalities of cellular DNA content and survival. Eur J Cancer Clin Oncol. 1985; 21(2):185-9. DOI: 10.1016/0277-5379(85)90171-3. View

16.

Culine S, Lortholary A, Voigt J, Bugat R, Theodore C, Priou F . Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol. 2003; 21(18):3479-82. DOI: 10.1200/JCO.2003.12.104. View

17.

Le Chevalier T, Cvitkovic E, CAILLE P, Harvey J, Contesso G, Spielmann M . Early metastatic cancer of unknown primary origin at presentation. A clinical study of 302 consecutive autopsied patients. Arch Intern Med. 1988; 148(9):2035-9. View

18.

Califano J, Westra W, Koch W, Meininger G, Reed A, Yip L . Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin. J Natl Cancer Inst. 1999; 91(7):599-604. DOI: 10.1093/jnci/91.7.599. View

19.

Palmeri S, Lorusso V, Palmeri L, Vaglica M, Porta C, Nortilli R . Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site : results of an Italian multicenter, randomized, phase II study. Cancer. 2006; 107(12):2898-905. DOI: 10.1002/cncr.22379. View

20.

Bugat R, Bataillard A, Lesimple T, Voigt J, Culine S, Lortholary A . Summary of the Standards, Options and Recommendations for the management of patients with carcinoma of unknown primary site (2002). Br J Cancer. 2003; 89 Suppl 1:S59-66. PMC: 2753014. DOI: 10.1038/sj.bjc.6601085. View