AUA 2017: European Association of Urology (EAU) Lecture: Genomic Revolution in Bladder Cancer: Fast Approaching or a Distant Dream?
Unfortunately, both local and distant failures are common as a result of delayed, inadequate or inappropriate local and systemic treatment, or inaccurate staging. Bladder sparing approaches have made a limited impact for a multitude of reasons and bladder cancer management is at high economic cost. Unselected use of cisplatin based systemic chemotherapy has shown a 5% overall survival benefit and has been incorporated to numerous clinical guidelines. However, at this time, we are unable to predict which patients are not helped or even hurt by chemotherapy, either from delay in surgical extirpation, or significant chemotherapeutic complications.
Improved technology and advancing knowledge have also supported the genomic revolution. Frozen tissue in the past was laborious and expensive to handle while newer FFPE tissue has the benefits of routine care, easier handling, and cheaper storage.
Recent studies have proposed mechanisms of cisplatin resistance. In one such study from Dr. Catto’s laboratory, a mutation in a basic enzyme in the processing of cysteine to glutathione inhibited cisplatin based DNA damage within a cell. Similarly, the Van Allen lab examined ERCC2 mutations, and its impact on resistance to cisplatin and radiotherapy.
The idea of precision medicine has been supported by both the United States and United Kingdom, with significant governmental funding to build data, tools and systems, develop regulations, and to sequence both rare diseases and common cancers.
Molecular guided therapy may help predict which patients have better results from neoadjuvant chemotherapy administration, to better select our targeted population and survival outcomes. Specifically, using TCGA sequencing, three different labs have demonstrated that basal cell subtypes have worse outcomes, but have significant improvement following neoadjuvant chemotherapy. This differs from other subtypes that may not have outcome improvements neoadjuvant chemotherapy. This finding may suggest that genomic and molecular cell types may help determine treatment protocols in the future. Similarly, immunotherapy offers an interesting option in the future, and immunohistochemical subtyping may predict treatment response.
This is an exciting time in the realm of bladder cancer and bladder cancer genomics, with promising changes on the horizon over the next decade.
Presented by: James Catto, MB, CHB, PhD, FRCS
Institution: University of Sheffield
Written By: David B. Cahn, DO, MBS, Fox Chase Cancer Center, Philadelphia, PA
Twitter: @dbcahn
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA