The following is a summary of “Actionable genomic landscapes from a real-world cohort of urothelial carcinoma patients,” published in the March 2023 issue of Urologic Oncology by Gerald et al.

The promising targeted therapies for advanced and metastatic urothelial cancer have sparked an interest. However, the actionable genomic landscape of early-stage disease remains largely unidentified. In this study, a substantial real-world cohort was employed to thoroughly examine the frequency of genetic modifications that may have therapeutic implications across all phases of bladder cancer. The NGS data of 1,562 bladder cancer patients (stages I-IV) were retrospectively analyzed. The tumor biopsies were formalin-fixed and paraffin-embedded and sequenced using the Tempus xT solid tumor assay. The frequency of genetic modifications, tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 status was evaluated and categorized based on the stage of bladder cancer. 

In the case of patients who underwent tumor-normal match sequencing (n=966), an evaluation was conducted to determine the presence of incidental germline alterations in 50 genes. The cohort comprised 165 tumors in stages I-II, 211 in stage III, and 1,186 in stage IV. The study observed Tumor Mutational Burden (TMB) high, Programmed Death-Ligand 1 (PD-L1) positive, and Microsatellite Instability (MSI) high status in 14%, 33%, and 0.7% of tumors, respectively, which exhibited similar prevalence rates across different stages. Similar frequencies of alterations in fibroblast growth factor receptor (FGFR)2/3, homologous recombination repair genes, additional DNA repair gene mutations (ERCC2, RB1, FANCC), and NTRK fusions were observed across various stages of the disease. 

A low incidence of incidental germline mutations was detected in all tumors (5.2%), as well as in certain genes such as MUTYH (1.9%), BRCA2 (0.5%), and ATM (0.8%). At all stages, significant subsets of patients exhibit genetic modifications in molecular pathways that may be addressed. The present study reveals limited diversity in these genetic changes throughout the different stages of bladder cancer. This underscores the importance of timely detection of genetic mutations and customization of treatment strategies for patients with bladder cancer, regardless of the stage of the disease.

Source: sciencedirect.com/science/article/abs/pii/S1078143922004938