The utility of next generation sequencing in advanced urothelial carcinoma

Biomarker-driven clinical trials are crucial for improving outcomes in patients with advanced urothelial carcinoma (aUC). Multiplatform genomic analyses utilizing next generation sequencing of tumor tissue and cell-free circulating tumor DNA have provided novel insights into the biology of UC and identified several molecular subtypes with potential therapeutic implications. Several "targetable" genomic alterations have been identified, such as those involving Fibroblast Growth Factor Receptor (FGFR), Human Epidermal growth factor Receptors, DNA damage response pathway, among others. Agents targeting those pathways have demonstrated encouraging efficacy in early clinical trials, while the FGFR inhibitor erdafitinib received accelerated approval by the FDA for platinum-refractory metastatic bladder cancer harboring FGFR2/3 alterations. Identification and validation of targets and potential biomarkers predictive of response will be crucial for successfully incorporating novel therapeutic strategies in the evolving treatment landscape of aUC. Standardization of molecular profiling, regarding assay, timing, origin of tumor specimen and other parameters may enable a more systematic assessment of clinical utility. PATIENT SUMMARY: 'Personalized cancer therapy' aims to tailor treatments to the characteristics of an individual patient's tumor. Next generation sequencing analyzes genes in a patient's tumor sample to identify abnormalities unique to his/her cancer. Clinicians can attempt to use this information to select the best treatment at the right time. This approach has shown significant promise and resulted in the approval of a new therapy for certain patients with advanced urothelial cancer; however, more work is required for broader impact and added value in patient care overall.