AUA 2018: Debate: Molecular Subtypes: Not Ready for Prime Time

San Francisco, CA ( David McConkey, MD, provided a rebuttal to Peter Black, MD, suggesting that molecular subtyping is not yet ready for ‘prime-time’. The previous work done with basal and luminal subtypes suggests that there is potential clinical utility according to McConkey. Several important points regarding basal and luminal subtypes:

  • We can identify patients who will and will not benefit from neoadjuvant chemotherapy (basal versus other)
  • We can identify patients who will (GU) or will not (luminal papillary/uroA) benefit from immunotherapy
  • We can identify variant histologies (ie. micropapillary, neuroendocrine, etc)
  • We can identify high risk pT1 and/or pT2 tumors, specifically with regards to the basal subtype
A group of experts recently met at GU ASCO 2018 to develop a consensus statement for molecular subtyping. There was support for developing a single-sample TCGA classifier, as well as recent identification of a neuronal/neuroendocrine subtype that according to Dr. McConkey appears to be very clinically significant. Based on this first meeting, there will be forthcoming refinements to this statement. 

McConkey makes several important points as to why we need to wait on molecular subtyping before it is ready for ‘prime time’. First, the basal subtype neoadjuvant chemotherapy benefit has not been confirmed in prospective trials. Second, a similar argument can be made for the relationship between molecular subtypes and response to ICB. Finally, we do not know whether molecular subtyping is an ‘intrinsic’ property of a given tumor. 

McConkey concluded this rebuttal talk by noting that clinical correlations must be tested prospectively and this is where we are ultimately lacking for molecular subtyping. More work needs to be done to characterize the stability of subtype membership and immunohistochemistry is even further behind in this matter. For now, McConkey states that DNA-based biomarkers, such as DDR mutations and tumor mutational burden, appear to be the most robust entities. 

Presented by: David J. McConkey, Johns Hopkins University, Baltimore, MD

Written by:  Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA

Read the Opposing Presentation: Molecular Profiling Influences My Treatment Selection
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