Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients. Here, we report a case of a 31-year-old female UrC patient who underwent intensive therapy with three surgeries and five lines of systemic treatments, including chemo-, checkpoint inhibitor and tyrosine kinase inhibitor therapies. In addition, next-generation sequencing (NGS) analysis and an ex vivo drug-screening analysis were performed on patient-derived tumor cells and the results were implemented into the therapeutic decision-making. Finally, serum carcinoembryonic antigen (CEA) levels proved to be helpful for therapy monitoring during the whole follow-up period.

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.