Cancer of unknown primary origin: utility and futility in clinical practice


Metastatic cancer of unknown primary (CUP) origin is one of the 10 most frequent cancers in humans; it accounts for approximately 3% to 5% of all solid malignancies. Patients with CUP present with metastatic disease whose site of origin cannot be identified at the time of diagnosis despite a thorough history, physical examination and appropriate laboratory testing, histopathology investigations and modern imaging technology (including computed tomography, magnetic resonance imaging, and positron emission tomography).

Materials and methods
A “state of the art” review was written reflecting all articles retrieved through a PubMed Medline search with the keywords “cancer of unknown primary”, “occult primary tumor”, and “metastases of unknown origin”, with no limits regarding date of publication, type of article, or field.

CUP represents a heterogeneous group of malignancies that can be classified into distinct clinicopathological entities. Certain entities are included in favorable sub-sets that are responsive to systemic chemotherapy and/or locoregional treatment: these include poorly differentiated carcinomas involving the mediastinal–retroperitoneal nodes, peritoneal papillary serous adenocarcinomatosis in females, poorly differentiated neuroendocrine carcinomas, isolated axillary node adenocarcinomas in females, cervical and inguinal node involvement by squamous cell carcinoma, and any other single metastatic site of limited extension. In these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Therefore, invasive endoscopic and laparoscopic procedures are rarely warranted in the absence of symptoms. Patients who belong to the non-favorable sub-sets (mainly metastatic CUP involving the liver, lung/pleura, brain, bones, or multiple sites) or have a poor performance status have a dismal prognosis (average median survival of 4-8 months).

The current evidence does not support the hypothesis that palliative chemotherapy improves survival and/or quality of life in CUP patients who do not fit into any of the favorable sub-sets. Therefore, only low-toxicity empirical chemotherapy regimens should be offered to patients with a good performance status, and quality of life issues should be given priority for any choice of treatment.



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Original Articles
Cancer of unknown primary, Occult primary tumor, Metastases of unknown origin
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How to Cite
Airoldi, G. (2012). Cancer of unknown primary origin: utility and futility in clinical practice. Italian Journal of Medicine, 6(4), 315–326.