Incidence and Survival Trends in Cancer of Unknown Primary (CUP): An Analysis From the North Rhine-Westphalia Cancer Registry, 2007-2023.

BACKGROUND: The term "cancer of unknown primary" (CUP) refers to metastatic tumors whose origin has not been identified even after a comprehensive diagnostic evaluation. Patients with CUP generally have an unfavorable prognosis. We analyzed CUP incidence and survival trends in the German state of North Rhine-Westphalia (NRW) over a 17-year period. METHODS: We carried out a population-based analysis of data from the NRW Cancer Registry (2007-2023). CUP cases were identified for inclusion in accordance with the current ESMO criteria; DCO cases ("death certificate only") were excluded. Age-standardized incidence rates were calculated in reference to the old European standard population. Five-year relative survival (RS) was determined with period analysis for 2010-2015 and 2018-2023, and subgroup analyses were performed. RESULTS: Out of 48 574 cases of CUP that were noted in the registry, 21 085 were found to satisfy the current ESMO criteria. The age-standardized incidence of CUP fell markedly, from 6.5 per 100 000 person-years in 2007 to 2.2 per 100 000 person-years in 2023 (average annual percentage change [AAPC], -5.45%; 95% confidence interval [-6.49; -4.40]), while five-year RS rose from 14.7% to 21.8%. Of all types of CUP, squamous cell carcinoma was associated with the highest RS (42.8%), and adenocarcinoma and undifferentiated carcinoma with the lowest (14-15%). RS was lower in older patients. CONCLUSION: The marked decline in CUP incidence and the moderate improvement in its survival rate likely reflect advances in diagnosis and subgroup-specific treatment. CUP still carries a generally unfavorable prognosis, and more research is needed in molecular diagnosis and targeted therapies.