Background Upper tract urothelial carcinoma (UTUC) is a rare urological cancer that is still an important public health concern in many areas around the world. Although UTUC has been linked to a number of risk factors, to our knowledge no systematic review has been published on the overall incidence and prevalence of de-novo UTUC. This review aimed to examine the global epidemiology of UTUC to provide clinicians and public health specialists a better understanding of UTUC. Methods A systematic search was conducted on MEDLINE, Embase, and the Web of Science using a detailed search strategy. Observational epidemiological studies describing the incidence and prevalence of de-novo UTUC in adults were included, and the Joanna Briggs Institute checklist was used for critical appraisal and data extraction of the studies selected. Results The systematic search identified 3506 papers, of which 59 papers were included for qualitative synthesis. The studies selected included data ranging from the years 1943 to 2018. A comprehensive qualitative synthesis of the data was performed. UTUC incidence generally varied according to age (higher with increasing age), sex (unclear), race (unclear), calendar time (increased, stable, or decreased according to region), geographical region (higher in Asian countries), occupation (higher in seamen and printers), and other population characteristics. Prevalence was only reported by one study, which showed UTUC to have the highest incidence of the rare urogenital cancers in Europe. Conclusion This systematic review highlights an increased incidence of UTUC in certain groups, including increasing age and certain occupations such as seamen. The incidence of UTUC also varies between certain geographical regions. The trend of UTUC incidence for sex, race, and calendar time is less clear due to a wide variety of metrics used by the studies identified. More studies are also required on the prevalence of UTUC to understand its disease burden. Trial registration This review was registered on PROSPERO (registration number CRD42019134255).

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