IBCN 2018: Longitudinal Assessment of Multiplex Patient-Specific ctDNA Biomarkers in Bladder Cancer for Diagnosis, Surveillance, and Recurrence.
Rotterdam, The Netherlands (UroToday.com) The use of circulating tumor DNA (ctDNA) as a biomarker for disease staging at diagnosis, treatment response, and recurrence monitoring is an emerging field. In bladder cancer, the utility of ctDNA has shown promising results. Using a prospective cohort of 68 muscle-invasive bladder cancer (MIBC) patients treated with neoadjuvant chemotherapy, a panel of 16 tumor-specific mutations was designed (SignateraTM RUO) based on whole-exome sequencing of tumor and germline DNA. In total, we analyzed ctDNA from longitudinally collected plasma samples from 637 time points procured at diagnosis, during treatment, at cystectomy, and during monitoring until disease recurrence or up to 2 years follow-up.
IBCN 2018: RBM10: A New Bladder Tumor Suppressor Gene Involved in Alternative Splicing
Rotterdam, The Netherlands (UroToday.com) Whole-genome and -exome sequencing studies have recently uncovered a novel putative tumor suppressor gene, RBM10, which is mutated in 2-5% of bladder tumors as well as in lung adenocarcinoma, colon, and pancreatic cancer. RBM10 maps to the X chromosome; approximately 30% of the somatic mutations in tumors predict a premature stop codon and lead to loss of protein expression. RBM10 encodes an RNA-binding protein that modulates alternative splicing of genes involved in cell growth, proliferation, and apoptosis (i.e. NUMB, CREBBP, FAS, BCL-X).
IBCN 2018: Transcriptional Activation of Genes and Resistance to Palbociclib
Rotterdam, The Netherlands (UroToday.com) Zhichao Tong investigated the relationship between transcriptional activation of genes and resistance to palbociclib to understand the molecular mechanisms and to further develop potential combination therapies for personalized therapy.
IBCN 2018: Molecular Markers and Clinical Outcome of Radical Cystectomy for Bladder Cancer
Rotterdam, The Netherlands (UroToday.com) Laura Mertens analyzed the prognostic value of the FGFR3 mutation and IHC markers (p53, Ki-67) in a multi-center, multilab setting. They performed a multicenter retrospective cohort study which included 904 cN0M0, chemotherapy-naive patients who underwent radical cystectomy (RC) with pelvic lymph node dissection. The FGFR3 mutation status was examined using PCR-SNaPshot. p53 and Ki-67 expression were determined by standard IHC. FGFR3 mutation status, p53 (cutoff> 10%) and Ki-67 (cut-off>20%) expression levels were correlated to clinic-pathological parameters and disease specific survival (DSS).
IBCN 2018: PD-L1 Assays in Muscle-Invasive Bladder Cancer for First-Line Treatment with Atezolizumab and Pembrolizumab
Rotterdam, The Netherlands (UroToday.com) Markus Eckstein analyzed the performance and agreement of four FDA/EMA-approved PD-L1 assays to detect PD-L1 expression in tumor and immune cells in muscle-invasive bladder cancer (MIBC). 173 formalin-fixed, paraffin-embedded MIBC were analyzed on tissue microarrays with four cores (1 mm diameter) of each tumor. Stains were performed in certified laboratories on Ventana Benchmark Ultra (Ventana-assays) and Dako Link 48 (Dako-assays) autostainers.
IBCN 2018: HRAS Mutations in Early-Onset Bladder Cancer
Rotterdam, The Netherlands (UroToday.com) Robert Stöhrv discussed his research on HRAS mutations and bladder cancer. Bladder tumors of early-onset patients are rare and seem to exhibit unique features, both clinically and pathologically. The few available molecular studies observing a low frequency of the known alterations found in bladder cancer lead to the hypothesis of a different mutational profile between the various age groups.
Recently, a study of few samples of young patients reported a higher percentage of HRAS mutations among the early-onset cohort compared to elderly samples. Due to the low sample size, the impact of these alterations of the age of onset and the frequency among young patients remain unclear and need further investigation.
IBCN 2018: PD-L1 Expression According to Five Monoclonal Antibodies in Urothelial Cell Cancer
Rotterdam, The Netherlands (UroToday.com) High PD-L1 expression is frequently applied as an inclusion criterion or stratification factor in clinical trials on immune checkpoint inhibitors (ICIs). However, conflicting results have been published regarding the predictive and prognostic value of PD-L1 expression in urothelial cancer (UC), which may be confounded by the use of different PD-L1 companion diagnostics. The objective of this study was to compare PD-L1 expression of five commercially available PD-L1 antibodies in muscle-invasive UC.