Cancer of unknown primary-structure of interdisciplinary treatment

Background: Cancer of unknown primary (CUP) still represents a diagnostic and therapeutic challenge. The prognosis of CUP is poor in most cases, especially in patients with unspecific CUP syndrome, with a median overall survival of 4-8 months. These patients can be differentiated from those with specific CUP syndrome, in which prognosis is significantly better. New insights: Newly designed interdisciplinary diagnostic algorithms enable easier classification of CUP to specific groups. Treatment of specific CUP subtypes is oriented toward treatment of the presumably equivalent primary tumor. First-line treatment of unspecific CUP has so far been based on a platinum-based chemotherapy doublet such as carboplatin/paclitaxel. The CUPISCO study recently presented at the European Society of Medical Oncology (ESMO) congress shows that next-generation sequencing before first-line therapy should be the new standard in unspecific CUP patients. These patients should be presented in a molecular tumor board to determine which targeted therapy or immunotherapy is to be applied. However, it is currently unclear whether this should be done early, as in CUPISCO (here after 3 courses of chemotherapy), or later on, when first-line therapy has failed. For almost all drugs, it is currently necessary to apply for cost coverage fromthe respective health insurance company. Conclusion: The complex strategy of diagnosis, initiation, and interpretation of molecular profiling as well as implementation of sequential therapy suggests that patients with CUP syndrome should ideally be referred to specialized cancer centers for determination of diagnosis and treatment.