IBCN 2024: Highlights
The highlight of day two was a thematic session discussing antibody-drug conjugates (ADCs). Srikala Sridhar discussed the toxicity of different agents and ongoing clinical trials. Markus Eckstein discussed mechanisms of resistance of ADCs, including target plasticity, microenvironment factors, and acquired or preexisting payload and binding site resistance mechanisms.
Several impactful abstracts were presented over the weekend, including the following highlights:
Comprehensive Genomic Characterization of Early-Stage Bladder Cancer
Philippe Lamy presented a study of comprehensive genomic characterization from 438 patients with NMIBC, including cohorts from UROMOL (n=296) and Aarhus University Hospital (n=142). Whole exome sequencing, shallow whole exome sequencing, and total RNA sequencing were performed. The most frequent mutations were seen in FGFR3, KDM6A, and KMT2D. Whole genome doubling was found in 15% of tumors and associated with increased risk of progression. An integrative clustering analysis comprised copy number alterations, mutations, and gene expression to develop new genomic subtypes. This includes low-risk iClus1, 2, and 3, as well as iClus4, which is defined as high-risk. These groups improve risk discrimination compared to previously used transcriptomic classes in NMIBC.
Correlation of Circulating Tumor DNA (ctDNA) Dynamics with Clinical Response in Muscle-Invasive Bladder Cancer (MIBC) Patients Undergoing Trimodality Therapy (TMT)
Kent Mouw presented one of the first studies describing ctDNA dynamics following TMT. The study evaluated pretreatment ctDNA results using the commercially available Signatera assay from 30 patients undergoing TMT. Of these, 22 patients had both pre- and post-RT ctDNA available. Of the 13 patients initially ctDNA negative, all remained negative. Of the nine patients who were ctDNA positive, five converted to ctDNA negative post-RT, and four remained ctDNA positive. The study was noted to be limited by its retrospective nature, limited sample size, and follow-up. We look forward to seeing future directions from expanded cohorts and follow-up in the future.
Spatial Proteomics and Transcriptomics Reveal an Altered Immune Cell Landscape in Bladder Cancer Patients Unresponsive to BCG Treatment
Trine Strandgaard presented data from spatial analyses of patients treated with BCG. This included immunohistochemistry (PD-1/PD-L1) from 168 tumors from 105 patients, GeoMx Digital Spatial Profiling (DSP) whole transcriptome analysis (WTA), and proteomics from 152 tumors from 101 patients, and imaging mass cytometry (IMC) from 68 tumors from 58 patients. After BCG treatment, patients showed increased CD4 (p<0.001), CD8 (p=0.004), and macrophages (p=0.020) compared to pretreatment cell counts. Spatial analysis revealed tissue localization of cells with enrichment after treatment. The authors concluded that BCG treatment alters immune cell infiltration, and pre-BCG immune cell abundances may affect outcome. Improving our understanding of the tumor microenvironment may deepen insights into the biological basis for patient outcomes.
First Translational Correlates Using Urinary Genomic Disease Burden to Assess Cretostimogene Grenadenorepvec: Comprehensive Analysis from the BOND-003 Trial in BCG Unresponsive, High Risk, Non-Muscle Invasive Bladder Cancer
Colin Dinney presented data on urinary genomic disease burden from patients in the BOND-003 trial using urine cell-free DNA (UroAmp). Pretreatment baselines were available for 64 patients, and post-treatment analysis was available for 51 patients at three months. The genomic disease burden response showed a reduction in aneuploidy and altered ERBB2, TP53, and RB1 mutations at three months compared to baseline. Patients who had reinduction at three mos and achieved a complete response had a significant reduction in genomic disease burden. Patients classified as UroAmp negative at three months had an 80% RFS at 12 mos. Patients classified as UroAmp positive at three mos had a 33% RFS at 12 mos (p=0.012). Longitudinal urinary genomic disease burden assessment using urine cell-free DNA can be used to quantify treatment response and may be used to support future treatment allocation trials to guide treatment intensity.
Written by: Amanda Myers, MD, Urologic Oncology Fellow, University of Texas, MD Anderson Cancer Center, Houston, TX
Adapted from the International Bladder Cancer Group (IBCG) Newsletter 2024 Vol 3