Carcinoma of unknown primary: focused evaluation.

The management of carcinoma of unknown primary (CUP) has evolved over the past decade, with the advent of sophisticated imaging and pathologic tests. Especially in the era of tailored therapeutics, this presents both an opportunity and a challenge. For the initial workup of a patient with CUP, a focused search for the primary cancer based on clinical presentation is recommended. Exhaustive use of unnecessary imaging, invasive studies, and pathologic tests adds to patient discomfort, is associated with significant cost, and often has a low yield for detection of a primary cancer. Physicians should be able to justify the need for ancillary tests and how results may impact the comprehensive management of patients. Over the next several years, physicians also need to focus their efforts on refining CUP subsets (e.g., isolated nodal, osseous, carcinomatosis presentations) and leveraging selective genomics and proteomics techniques to eventually deliver validated new therapeutic approaches to patients. This will require creative approaches to clinical studies, including establishment of international CUP cooperative groups and innovative designs. Just as physicians need to be selective in their diagnostic approach, they also need to be selective in their research efforts as they continue to impact quality of life and survival for patients with CUP.