AUA 2020 Review: Genomic Heterogeneity in Tissue-Based Prognostic Signatures from Prostate Biopsies: The Results From Two Prospective Trials - Thomas Keane

Thomas Keane reviews “Genomic Heterogeneity in Tissue-Based Prognostic Signatures from Prostate Biopsies: The Results from Two Prospective Trials” which was accepted for presentation at the virtual American Urological Association (AUA) 2020 meeting. Considering the challenge men with prostate cancer face in choosing between active surveillance and treatment, Dr. Keane discusses how the performance of these prognostic tests may be impacted by tumor heterogeneity.


Thomas E. Keane, MBBCh, FRCSI, FACS, Department of Urology, The Medical University of South Carolina, Charleston, South Carolina, USA.

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Tom Keane: Good morning everybody, this is Tom Keane coming to you from UroToday in Charleston, South Carolina at the Medical University of South Carolina. Today, I'm going to take a look at some of the moderated poster abstracts which were accepted for presentation at the AUA, which of course, there is a virtual one taking place, but the actual AUA did not take place this year. And in this, it was Prostate Cancer Marker Session 1. And I would like to focus first of all, on abstract number MP09-01. This was entitled "Genomic Heterogeneity in Tissue-Based Prognostic Signatures from Prostate Biopsies: The Results From Two Prospective Trials". And the primary author on this was a Venkata Sai Atluri, and it came from Miami.

And the authors pointed out that tissue-based prognostic signatures have been used in various stages of prostate cancer, including biopsy tissue from men who are deciding between active surveillance versus treatment. Now all of us have faced this in the clinic. Whom do we treat, whom do we not treat? And there are many factors that are considered prior to making a definitive decision. Some patients just will not tolerate the idea of having cancer and regardless of what you say, they want to have active treatment. Others may have the completely opposite view and it's a question of trying to decide what is and what is not the best solution for them.

So recent studies have suggested that these tests may be affected by tumor heterogeneity impacting their performance for appropriate risk stratification. The authors evaluated the performance of tissue-based prognostic signatures on biopsy tissue from two ongoing prospective trials in men with prostate cancer at the University of Miami. In their methods, the positive cancer cores in the Miami Active Surveillance trial, or the MAST trial, and diagnostic and targeted biopsies in the BlastEM trial were sent for genomic sequencing. This study reports on preliminary results from both trials on men whose biopsy cores were sequenced at GenomeDx and evaluated for three commercially available gene signatures namely the GenomeDx Decipher® genomic classifier, Oncotype DX® Genomic Prostate Score, and Myriad Prolaris® Cell Cycle Progression Score. Now, these three different tests make up the primary assessment really that takes place in a lot of centers regarding how significant a cancer this is. So this was an interesting abstract.

Now the results, the current cohort consisted of 78 men from the MAST trial and the Blast trials. There were 46 from the MAST and 32 from the Blast trials. There were 231 biopsy cores, which were sent to GenomeDX® for genomic sequencing. The findings were that for each signature, there was a trend towards higher scores with higher grade groups. However, each signature displayed a significant degree of variation within each grade group, which was significant. And there's a figure. Figure one demonstrates this. When assessing genomic scores from different cores, the authors found significant variability, which is also illustrated in figure two with the level of genomic risk within each biopsy session changing by 25 to 62%, depending on which core was sequenced and which signature was used. So typically, in clinical utility, the genomic score is used for the highest grade of the tumor, but the authors found that an average 80% of the time, the highest genomic score did not come from the highest grade group in all the three commercially available gene signatures.

So the conclusion is that there exists a significant degree of genomic heterogeneity between biopsy cores, and this may have implications when considering the reliability of these signatures in biopsy tissue. Now, again, it's somewhat disturbing these findings because a lot of us will put a lot of faith into these genomic scores, depending on which one you like to use. It's not usual that we have significant comparisons between the three. So this is something for people to consider when they're considering how they're going to assess whether or not this patient has more advanced disease or perhaps is more deserving of, not deserving, but requires active treatment as opposed to active surveillance. So we'll see what happens. I'm sure there'll be a paper published on this in the future.