Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumors that appear as metastases for which a standard diagnostic work-up fails to identify the tissue of origin. There is now high-level evidence showing that actionable genomic alterations should be routinely determined in patients with CUP to enable molecularly guided therapy as appropriate. In this guideline (updated in 2025), we summarize diagnostic processes and therapeutic options for CUP, as well as new developments in molecular medicine that will help to improve the poor outcomes associated with this unique disease entity.
Losa et al. (Tue,) studied this question.