Cancer of Unknown Primary

Approach to Cancer of Unknown Primary:
Cancer of Unknown Primary (CUP) is when a tumor is detected at one or more metastatic sites, and routine evaluation fails to define a primary site. Up to 70% of CUP are adenocarcinomas. The initial workup of patients presenting with presumed CUP should not be exhaustive but should focus on likely primary sites including:
a thorough history and physical examination (including a pelvic examination in women and a prostate examination in men), complete blood count, urinalysis, chemistries, a chest radiograph or CT scan of the chest, and CT of the abdomen and pelvis. Mammography should be considered in women with a clinical presentation compatible with metastatic breast cancer

Measurement of common tumor markers (carcinoembryonic antigen, CA 19-9, CA 15-3, and CA-125) should not be used as diagnostic or prognostic tests

The prognosis of patients with CUP is unaffected by whether the primary lesion is ever found. Unfavorable prognostic features include: multiple metastatic sites, well-differentiated or moderately differentiated adenocarcinoma histology, older age, and lower performance status.

Bisphosphonates reduce the morbidity of metastatic bone disease, mainly by decreasing the prevalence of skeletal related events.

Bisphosphonates, when administered to mice with osteolytic lesions, have decreased bone lesions, as expected, but also a decrease in tumor burden. Similarly, mice that are treated with neutralizing antibodies to PTHrP, as well as tumors that express mutant TGF-β receptors, experience a decrease in tumor burden. There is a rationale for developing clinical inhibitors of the bone-resorption process, as so much data now indicates that osteolysis supports the growth and aggressive behaviour of metastatic cancers.

(Ellen Eaton MD, 5/20/11)