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.