OBJECTIVES To investigate incidence, mortality and case survival trends for cancer of unknown primary site (CUP) and consider clinical implications.   
 METHOD South Australian Cancer Registry data were used to calculate age-standardised incidence and mortality rates from 1977 to 2004. Disease-specific survivals, socio-demographic, histological and secular predictors of CUP, compared with cancers of known primary site, and of CUP histological types, using multivariable logistic regression were investigated.   
 RESULTS Incidence and mortality rates increased approximately 60% between 1977--80 and 1981--84. Rates peaked in 1993--96. Male to female incidence and mortality rate ratios approximated 1.3:1. Incidence and mortality rates increased with age. The odds of unspecified histological type, compared with the more common adenocarcinomas, were higher for males than females, non-metropolitan residents, low socio-economic areas, and for 1977--88 than subsequent diagnostic periods. CUP represented a higher proportion of cancers in Indigenous patients. Case survival was 7% at 10 years from diagnosis. Factors predictive of lower case survival included older age, male sex, Indigenous status, lower socio-economic status, and unspecified histology type.   
 CONCLUSION Results point to poor CUP outcomes, but with a modest improvement in survival. The study identifies socio-demographic groups at elevated risk of CUP and of worse treatment outcomes where increased research and clinical attention are required.
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