Society of Urologic Oncology (SUO) 21st Annual Meeting

SUO 2020: Molecular Characterization of NMIBC in the Clinical Context

(UroToday.com) In this presentation, opening the session on bladder cancer at the Society of Urologic Oncology (SUO) 2020 meeting, Dr. Sfakianos gave a summarized overview of the molecular characterization of non-muscle invasive bladder cancer (NMIBC).

In order to treat NMIBC appropriately, it is critical we understand the biology of the disease, the various prognostic markers, have available biomarkers to assess treatment response or resistance, and continue to develop novel therapeutic options.

In a landmark study published in 2016, the authors performed total RNA sequencing of NMIBC from 460 patients in Europe. The authors discovered that early-stage bladder cancer could be sub-grouped into distinct classes (figure 1) with basal- and luminal-like characteristics like those of muscle-invasive bladder cancer1. This classification had important implications for treatment and prognostication and can result in the development of targeted agents and optimized disease management.

Figure 1 – Delineation of Molecular Classes in Early-Stage Bladder Cancer1:

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Next-generation sequencing of NMIBC has revealed potential ad rational therapeutic targets2. Some of the findings of an important study published in European Urology journal2 in 2017 include the findings that TERT promoter mutations (73%) and chromatin-modifying gene alterations (69%) were highly prevalent across grade and stage of NMIBC tumors. Additionally, ERBB2 or FGFR3 alterations were present in 57% of high-grade NMIBC tumors in a mutually exclusive pattern. DNA damage repair (DDR) gene alterations were seen in 30% (25/82) of high-grade NMIBC tumors, and ARID1A mutations were associated with an increased risk of recurrence after BCG2 (Figure 2).

Figure 2- An overview of the genomic landscape of NMIBC by grade and stage with comparison to MIBC2:

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Detailed genetic analyses of high-grade T1 NMIBC bladder tumors have identified features that correlate with outcome. For example, high mutational burden, ERCC2 mutations, and high APOBEC-A/ERCC2 mutation signatures have been shown to be associated with good outcome3 (Figure 3).

Summarizing his talk, Dr. Sfakianos stated that there is significant heterogeneity in NMIBC at many levels. Therefore, it is imperative that we ask focused questions, perform a comprehensive analysis of tumors, and pursue collaborations with various institutions to improve treatment options.

Figure 3 - Proposed treatment algorithm based on main genomic characteristics predicting outcome in HGT1 bladder cancer3:

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Presented by: John Sfakianos, MD, Assistant Professor of Urology and Urologic Oncology at the Mount Sinai- School of Medicine, New York, New York

Written by: Hanan Goldberg, MD, MSc, Assistant Professor, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, @GoldbergHanan during the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC

References:
1. Hedegaard J, Lamy P, Nordentoft I, et al. Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma. Cancer cell 2016; 30(1): 27-42.
2. Pietzak EJ, Bagrodia A, Cha EK, et al. Next-generation Sequencing of Nonmuscle Invasive Bladder Cancer Reveals Potential Biomarkers and Rational Therapeutic Targets. European urology 2017; 72(6): 952-9.
3. Bellmunt J, Kim J, Reardon B, et al. Genomic Predictors of Good Outcome, Recurrence, or Progression in High-Grade T1 Non-Muscle-Invasive Bladder Cancer. Cancer research 2020; 80(20): 4476-86.

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