The site of origin of a histologically documented carcinoma is not identified clinically in approximately 3% of patients; this situation is often referred to as carcinoma of unknown primary (CUP) origin or occult primary malignancy.[1,2,3,4,5,6]
Incidence and Mortality
Bladder cancer is the sixth most common cancer in the United States after lung cancer, prostate cancer, breast cancer, colon cancer, and lymphoma. It is the third most common cancer in men but only the eleventh most common cancer in women. Of the roughly 70,000 new cases annually, about 53,000 are in men and about 18,000 are in women. Of the roughly 15,000 annual deaths, over 10,000 are in men and fewer than 5,000 are in women. The reasons for this disparity between...
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.
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.[7,8,9,10]
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. 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.