Ashley Ross: Hi everyone. This is Ashley Ross. I'm a urologist at Northwestern. I'm glad to be here for you today and joined by Dr. Winer. Dr. Winer is the Associate Professor of Urology and Residency Program Director at SUNY Downstate. He's also the Chief of Urology at NYC Health and Hospitals, King County. Recently, Dr. Winer has put forth some data on genomics, specifically in the African American population. And we wanted to have him on to talk about his work and then have a little discussion about genomics and other advanced testing, specifically in minority populations. Dr. Winer, thanks so much for being here.

Andrew Winer: Thank you so much. I'm really honored to join you here today, Dr. Ross. Privileged to be able to share our data from our recent publication. So, I think the discussion surrounding genomics in the use of active surveillance is a hot topic. It's one that is not definitively solidified in our field. But in particular, I think active surveillance still remains somewhat of a question within the minority population, in particular Black men.

Andrew Winer: And so, in this recent publication, we sought to look at NCCN risk reclassification in Black men with low and intermediate-risk prostate cancer after genomic testing. I have no disclosures. And just a bit of background, that many of you already are aware of, prostate cancer in Black men as compared to white men transforms earlier into more clinically significant disease, grows at a faster rate, and often metastasizes earlier.

Andrew Winer: And this disparity, it's unclear as to what drives it at this point. But we know that there are modifiable socio-economic factors at play, as well as environmental factors. But there is a molecular or genetic, epigenetic, component to this. And the interplay between these factors is yet to be elucidated.

Andrew Winer: We know that active surveillance has increased in its utilization over the past two decades. And I think we can agree that this has been a paradigm shift for the better for patients. And most published series on active surveillance, though, are composed of less than 10% Black patients. And this is despite the fact that Black men constitute the United States's largest population of prostate cancer patients. So the NCCN guidelines, as we are aware of, they have moved the active surveillance recommendation to the preferred modality for most patients. And to consider interventions like molecular tumor analysis in certain cases to help risk stratify.

Andrew Winer: And when you pull that down into a little bit more granular principles of risk stratification, we can look to see that there are newer risk classification schema that have been shown to outperform NCCN risk groups and the use of adjunctive tools such as imaging, gene expression biomarkers, can be used. In particular, with patients with low and unfavorable intermediate-risk disease, we can use things like molecular assays, Decipher, Oncotype, and Polaris, to help in that risk classification to help make a very difficult decision, maybe a little bit easier for the patient and the provider.

Andrew Winer: Just a minute on biomarkers. As we know, they can help aid, in differentiating clinically significant versus indolent disease. And they've been proposed for the assessment of prognosis, early detection, and predicting outcomes. And at the bottom here, you can see there's a whole concoction of different options available to each and every one of us.

Andrew Winer: And Dr. Ross, I'm not sure which of these you use in your practice, but I certainly know that I use a variety of them for different patients. But in our practice, we predominantly use Oncotype DX Genomic Prostate Score. And I think this goes to a lot of people, preference is institutionally biased. What an institution will allow you to proceed with and what gets reimbursed in your patient population.

Andrew Winer: And so we prefer the GPS score because we leverage the success with breast cancer in our patient population. And so we have been able to piggyback off of their success and use it in our patients. And it's performed on prostate biopsy tissue samples. And what it does is it analyzes the up and down-regulation of 17 genes across multiple genetic pathways. And in conjunction with clinical factors, this yields probabilities of pathology, prostate cancer, death, and mets at 10 years.

Andrew Winer: Most importantly for me though, it helps provide a new NCCN risk classification based on these molecular results. So the aim of our study was to look at the concordance between the originally assigned NCCN risk classification with a newly assigned risk classification after genomic testing, in a 100% African-American or Afro-Caribbean patient population.

Andrew Winer: So Active Surveillance protocol just briefly is for very low, low, and favorable intermediate-risk patients. We perform an immediate Oncotype on all of our patients to confirm the biologic risk potential. And if the Oncotype confirms appropriate risk, then these patients can proceed on to Active Surveillance. Perform a DRE/PSA biannually, an MRI at 12 months after initial biopsy, and a confirmatory biopsy at 12 to 24 months.

Andrew Winer: We identified 63 men, and you can see the breakdown here. The highest predominance was 38% at low risk, and 49% had favorable intermediate risk. And all received Oncotype prior to the initiation of Active Surveillance, and a median follow-up time of 17 months.

Andrew Winer: The key takeaways for me, the key study findings were that in aggregate, classification after GPS testing showed that there was significantly higher risk classification than the initial risk classification. So it was upstaged in a good portion of these, and that was statistically significant.

Andrew Winer: And of the 63 patients, 40 patients, 63.5%, had changed in their risk designation. This could have been higher or lower. And among the patients with discordant risk designations, so that was 40 patients, 28 of those patients had higher biological risk after genomic testing. So over 60% are changing towards a higher risk strata. And of the 31 favorable intermediate- risk, 65 were upstaged.

Andrew Winer: I want to give a shout-out to my rockstar residents Stanley Wang and Ben Side, and for putting this diagram together. I think this nicely demonstrates what we just showed in the last slide, which is that when you have the original NCCN classification, there is a pretty significant departure when you add in a genomic prostate score. So you can go from very low to low, but really when you look at low and favorable intermediate risk, there is a pretty significant departure from the original classification. And in the intermediate risk group, this was substantially towards higher staging. So we had a number go up to unfavorable intermediate risk, and then three even went up to high risk.

Andrew Winer: I will point out that 18 of these patients ended up undergoing definitive therapy. 11 surgeries, seven radiation. But these numbers were too small to make any significant clinical statement based on them.

Andrew Winer: Some limitations. Obviously, there's retrospective and a relatively small sample size at 63. But a very unique patient population, in my opinion. A short follow-up period, when we're talking about prostate cancer and prostate cancer outcomes. And this may have also contributed to the small number of patients receiving definitive therapy. As we know, Active Surveillance requires long years of monitoring to really make any changes.

Andrew Winer: So in conclusion, we really identified that the incorporation of genomic testing and risk stratifying black men with low and intermediate-risk prostate cancer resulted in overall, as an aggregate, higher NCCN classifications. And when you drill that down into the low and favorable intermediate-risk disease, a number of these, up to 65%m were upstaged. So this suggests, for me in my practice, a role for increased utilization of genomic testing and risk stratification within this unique and high-risk patient population.

Andrew Winer: So with that, I'll leave the presentation and I would be happy to answer any questions and have a dialogue. And certainly, if anybody in the community would like to reach out to me, I'd be happy to have a discussion offline as well.

Ashley Ross: Thank you so much for that, Dr. Winer, I think a couple of take homes that I got from your work. One was, as you noted, particularly in the favorable intermediate-risk category, there could be a lot of variation and movement towards a higher risk score genomically. The low-risk category, that also happens. Very low risk, they never skip two rungs. So let's start there and say for very low-risk prostate cancer patients, even African Americans that might have higher genomic scores, are you doing it in that population or do you find that the real utilities, once you get the NCCN low-risk favorable risk population?

Andrew Winer: Yeah. Great point. And really, I would think that's a good nuance to pick up on. I would say that you could safely obviate a genomic test in a very low-risk patient, even in this cohort. I think that our results show that it is pretty safe. That really, like you said, you could go from very low to low risk. But we would still continue that patient on Active Surveillance.

Andrew Winer: For me, it's a matter of capturing and really standardizing a protocol. So when you have a varied clinical practice, I think it's important to make sure that details aren't lost, in between residents that are coming through and new patients from our catchment area expands, as many practices out there expand beyond just the local area. We get visitors from other countries, the Caribbean. And so for me, it really benefits our patients, I think, to standardize the practice. So in that patient and those particular patients, I think it's pretty safe to skip the genomic test. But in our practice, we standardize it.

Ashley Ross: And then secondarily, as you mentioned, what you saw in the low and favorable intermediate-risk men is a fair bit of reclassification and reclassification to higher genomic scores. And in the traditional studies that were based on Caucasians, we saw that was less robust. And so it could be something about the African American population. There's a study using another genomic classifier, Decipher, called the Van Dam Study, that was presented at ASCO last year, I think by Kashi Imoda. And he showed some similar findings. I think almost 30% was going to this high genomic risk. And so I think it just highlights the African American population in particular.

Ashley Ross: Now you may have standardized this across Caucasians too, but in the African American population in particular, genomics may play a very important role in understanding who may not be a good candidate for Surveillance.

Ashley Ross: The other thing that you pointed out, and I just wanted, if I could pick your brain on it, some of the patients in your study had MRIs after they had their prostate cancer diagnosis. At least in my practice and based on a lot of the larger clinical trials and in my area, which is also important, these insurances are allowing for us to get MRIs prior to initial diagnosis. And that helps a lot. I think a lot of people that were maybe on the table for Surveillance are found in their target lesions to have a [inaudible 00:12:40] cancer, and they're not on the table anymore. And you find that out early. How are you incorporating MRI in your practice? Are you trying to get it before the biopsy? Are they allowing for that in your area? And how do you think that might change a little bit of what you do with the genomic testing?

Andrew Winer: Yeah, another great point. So I think when we did this study, which was from 2016 to really the follow-up continued out into 2020, we were just getting our bearings with pre-biopsy MRIs, and now it's pretty standard across the board. And it has changed to a certain extent, I would say. We certainly incorporated it, and it helps us reassure patients. And I think you could, again, safely skip the genomic testing when you have a reassuring MRI, pre-biopsy, a targeted biopsy to a specific lesion and it comes back as favorable pathology. I think that the utility of genomic testing there, it starts to really decline. But I would say that, still for me, I think that adds a layer. I've been burned a few times by these patients. I think we can put to rest the fact that Active Surveillance is safe or unsafe in African Americans. It is safe, correctly born out protocol. And I think you have to be potentially monitoring these patients. But I think that using adjunctive tests such as MRI and genomic testing is probably more important in this cohort, in my opinion.

Ashley Ross: And I would agree. What I do in my practice is, what I use the MRI for, is I try to do for biopsy. And I use it, 'cause if I find someone who has four plus three equal seven, which is [inaudible 00:14:38] pre-cancer, obviously I'm not really going to talk about surveillance, the [inaudible 00:14:41] life expectancy.

Ashley Ross: But if I find three three six, I often will reach to it for genomic test. I use Decipher in my practice, but Oncotype as well. I'll often reach for genomic tests. 'Cause like you said, even though it helps to hit the target lesion, there have been publications, both with Decipher and with Oncotype DX, that there is independent information in the genomics. And as you mentioned, you don't want to get quote-unquote burned, or the patients get burned with a quick progression. And you want to have good expectations for how long they could be on surveillance.

Ashley Ross: So again, a great study. Nice to validate this further in the African American population. My take home was that if anything, they're more African American, the percentage of them that are going to get up classified by their genomics to maybe a riskier status is a little bit higher than what we've seen in Caucasian populations. There could be some selection bias. We have to look at further studies. But this is a good tool. And you said it really well, African Americans are certainly candidates for Surveillance, but it might be important to really risk stratify them and understand their disease before you make that initial position. Any take homes on your end, Dr. Winer?

Andrew Winer: I think you hit the nail on the head. Really for me, we're very cost conscious right now. And so I understand that there is a move towards being more aware of healthcare costs, and financial toxicities within all of these cancers that you and I treat are exorbitant. And so to add another layer onto that for all of our prostate cancer patients, it seems maybe like it's not the best use of our dollars. But in my opinion, we are seeing a number of these slip through the cracks, or potentially. And I think what this study shows me is that there's more than meets the eye. When a pathologist looks at that tumor under a microscope, I want to know that it's not, a wolf in sheep's skin and that something biologically going on underneath the surface isn't going to come back and hurt this patient sooner rather than later.

Ashley Ross: Yeah. And I agree with you. And then you were touching on this. Just to use another old saying, you don't want to be penny wise, pound foolish. You sort of want to know, upfront spend a little bit more if need be with the genomics also, and understand if your patient is on this curve with their cancer. Are they on this curve with their cancer? Or are they on this curve with their cancer? So that you can then intervene definitively when it's time, and save them from unnecessary biopsies on Surveillance that might just show progression the next year or two years from then. Or if they're on this curve, I think the name of the game in my practice, and maybe a discussion for us in the future, is how intense or how active does the Surveillance need to be? And that's where we can save dollars if they have a low risk.

Andrew Winer: Absolutely. And if I feel good about the MRI, their pathology, and their GPS score, I'm pushing that boundary. So I'm actually probably ultimately saving some, if we want to just talk about cost, just in the long run, because we're not going as aggressively into that next biopsy.

Ashley Ross: Yeah. Well again, wonderful work. I really thank you for the opportunity to talk with us tonight, and to share this with us. Dr. Winer, I'm looking forward to having more of these conversations in the future.

Andrew Winer: Thank you so much. It was a pleasure. Anytime I would love to talk more.