As diagnosis and management of cancer of unknown primary (CUP) sites has become more personalized, a multidisciplinary approach among oncologists, pathologists and radiologists is essential, according to a review article published in the March issue of the American Journal of Roentgenology.

CUP accounts for 2 percent of malignancies in the U.S. However, there is a lack of consensus regarding the diagnostic workup for CUP, which can be a broad term that encompasses all types of malignancies. Subsets of CUP patients have tumors that are responsive to chemotherapy or locoregional therapy; such patients may be identified via imaging.

As the oncology team reviews the initial evaluation and biopsy and identifies studies for additional workup, selection of the appropriate imaging is critical, according to Kyung Won Kim, MD, from Dana-Farber Cancer Institute in Boston, and colleagues, who wrote, “nontargeted studies rarely detect the primary site and confusion can result from false-positive results.”

The authors emphasized the importance of a multidisciplinary strategy and wrote, “Radiologists must have a clear understanding of the clinical questions at hand, the goals and role of imaging at each diagnostic step, and imaging limitations.”

Radiologists’ roles include recommending the biopsy site and suggesting additional imaging exams, as well as preventing unnecessary and costly workups.

The cornerstone of the imaging strategy is contrast-enhanced CT of the chest abdomen and pelvis, which can help physicians search for the primary tumor, assess the extent of disease and possible spread and determine biopsy sites.

In contrast, the routine use of mammography in women with CUP remains questionable given its low detection rate.

The role of PET/CT in patients diagnosed with CUP is uncertain, and the 2013 National Comprehensive Cancer Network guidelines do not recommend the hybrid exam. However, it may be justified in select patients, such as those with squamous cell cancer who present with malignant cervical adenopathy, according to Kim et al. PET/CT also may help exclude distant metastases and inform locoregional therapy among patients with treatable disease.

Imaging findings and decisions should be made in the context of other clinical data, the authors emphasized. Serum tumor markers may be used to help narrow the differential diagnosis, while immunohistochemistry stains should be reviewed with morphologic data and clinical presentation to inform the final diagnosis. Finally, molecular profiling is increasingly used to predict the primary site and drive site-specific therapy.

The final role of imaging in patients with CUP is to assess response to therapy, noted Kim and colleagues. This application may expand as patients with CUP are treated with targeted therapy. However, the use of cytostatic agents requires imaging techniques that assess vascularity, density or parameter changes in functional imaging rather than size.

Kim and colleagues concluded by referring to the evolving management of CUP. “[Improvements] in care compel us to identify sites of primary disease when possible, a task much more important and sophisticated now than a decade ago.”