Genetic characteristics and targeted treatments of primary bladder and urachal adenocarcinomas: a systematic review with pooled descriptive genomic analyses

Adenocarcinomas are rare histological subtypes of bladder cancer mainly presenting as primary bladder adenocarcinomas (PBACs), or urachal carcinomas (UrCs). The lack of standardized, evidence-based clinical recommendations for therapy results in individualized treatment decisions. These personalized treatments may be tailored based on molecular analyses to target driver mutations. The genetic background of UrC and PBAC has been increasingly explored through molecular analysis of relatively small case series. Similarly, experiences with targeted treatments are available from individual case reports and single institution case series. Consequently, currently available genetic and targeted treatment data are fragmented, hindering a comprehensive overview and firm conclusions. Therefore, we aimed to catalogue and interpret recent molecular genetic insights and targeted therapeutic experiences in UrC and PBAC in order to provide a basis for improved clinical decision-making. In this review, we screened online databases with search terms selective for genetic and targeted therapeutic data in UrC and PBAC. Utilizing the extracted data, we identified mutational frequencies, created OncoPrints, investigated signaling pathways, and evaluated treatment approaches guided by precision medicine. Our summary of genetic findings and targeted therapy strategies are intended to support off-label options for UrC and PBAC.