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  • Review Article
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Carcinomas of an unknown primary origin—diagnosis and treatment

Nature Reviews Clinical Oncology volume 8, pages 701–710 (2011)Cite this article

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Abstract

Carcinomas of an unknown primary origin (CUP) account for 3–5% of all malignancies and are thus among the ten most-frequent cancers worldwide. Having a specific and unique phenotype of early and usually aggressive metastatic dissemination with no identifiable primary tumor, CUP are a challenge for physicians. The diagnostic workup of patients with CUP includes a careful clinical and extensive histopathological examination, as well as the use of imaging techniques. CUP can be divided into favorable and unfavorable subsets. Patients with unfavorable CUP subsets have a poor prognosis with a median survival of approximately 8 months; the optimal chemotherapy regimen for these patients remains to be determined. Although studies have focused on the introduction of new cytotoxic agents with broad-spectrum clinical activity (such as gemcitabine, irinotecan, and taxanes), no randomized trial has provided clear evidence of a survival benefit. Molecular targeted therapies that are approved for other solid tumors are now considered for the treatment of patients with CUP. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for 'lost' CUP origins. In this Review, we describe the clinical evaluation of patients with CUP, and discuss treatment strategies and outcomes of patients with various CUP subsets.

Key Points

  • 15% of carcinomas of an unknown primary origin (CUP) have an identifiable subcategory, including adenocarcinoma in axillary lymph nodes, peritoneal papillary serous carcinoma, squamous carcinoma involving cervical lymph nodes, and poorly differentiated neuroendrocrine CUP

  • The remaining 85% of patients that do not fit into these specific subgroups require empiric chemotherapy, which usually consists of cisplatin-based dual chemotherapy

  • Medical oncologists should use validated prognostic scores to define the treatment strategy; for example, the French prognostic score based on performance score and lactate dehydrogenase levels

  • In the future, genome-wide screening may change the management of patients with CUP

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Figure 1: Management of patients with CUP in 2011.

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  1. Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, 39 rue Camille Desmoulins, F-94800, Villejuif, France

    Christophe Massard, Yohann Loriot & Karim Fizazi

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C. Massard wrote the manuscript. All authors researched data for the article, provided substantial contributions to the discussion of content, and reviewed or edited the manuscript before submission.

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Supplementary information

Supplementary Table 1

Tumor-specific markers and their immunohistological staining pattern in CUP biopsies (DOC 45 kb)

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Massard, C., Loriot, Y. & Fizazi, K. Carcinomas of an unknown primary origin—diagnosis and treatment. Nat Rev Clin Oncol 8, 701–710 (2011). https://doi.org/10.1038/nrclinonc.2011.158

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