Heterogeneity in Multifocal Prostate Cancer - Simpa Salami
January 10, 2023
Simpa Salami, MD, MPH, Assistant Professor, Department of Urology, University of Michigan, Ann Arbor, MI
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
Transcriptomic heterogeneity in multifocal prostate cancer.
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Alicia Morgans: Hi, I'm so excited to be here with Dr. Simpa Salami who is visiting us from the University of Michigan. Thank you so much for being here.
Simpa Salami: Thank you so much for having me.
Alicia Morgans: Well, it is always a pleasure to talk with you. And I wanted to catch up with you because your PCF, Young Investigator Award, has been going on for a few years. It was awarded in 2016. First, before we get into the data and some of your findings, of course, and where you're going next, can you tell me how has this young investigator award impacted your career and trajectory?
Simpa Salami: This award really catalyzed my career as a young investigator in urology oncology. First, it gave me funds to support my research, but it also gave me funds to protect time to be able to engage in research as a surgeon, as you might imagine. And of course, integrated me into a very nice community of people of investigators that I can collaborate with, that I have been collaborating with over the years since I got this award.
Alicia Morgans: Wonderful. And to your point, as a surgeon in particular, you have clinical time in clinic and you also have OR time, where you're obviously actively operating on patients. And sometimes having that protected time can be really, really difficult. So you're a unique member of our PCF community, as a urologic investigator and scientist, and so we're very excited to have you. So to talk a little bit more about your award, can you let me know what was the premise of the award, and what have you accomplished so far in your investigation?
Simpa Salami: We know that prostate cancer is multifocal. That is, there are often multiple regions of cancer within the prostate when the prostate is removed, and there's a lot of heterogeneity from focus to focus as well as heterogeneity from patient to patient. And the question is, what is the biologically dominant nodule? That is to say when there are multiple areas of cancer in the prostate, what really is responsible for how the cancer will behave in that particular individual? That really was the question that we sought out to answer. And to do that, we assembled prostate cancer specimens from patients who had undergo radical prostatectomy and had lymph node dissection at the same time. And we performed DNA and RNA Next-Generation Sequencing to be able to compare the molecular profile of the cancers in the prostate with the cancer in the lymph nodes.
Alicia Morgans: Wonderful. And where did you publish this work? This is something I think that's come out already, right?
Simpa Salami: Yes, yes. The first paper was published in 2018 in the Journal of Clinical Investigation Insight. The paper we titled Transcriptomic Heterogeneity in Multifocal Prostate Cancer.
Alicia Morgans: And what was the take home message there?
Simpa Salami: The punchline is that the heterogeneity in multifocal prostate cancer impacts the performance of biomarkers that are available today for use in risk stratifying patients into aggressive versus indolent prostate cancer. When we assess the performance of biomarkers in low grade versus high grade disease within the same patient, there was significant difference, suggesting that if you were to biopsy a patient and you found low grade disease in the biopsy specimen, that the information you obtain molecularly cannot inform you if you've missed a high grade disease elsewhere in the prostate.
Alicia Morgans: This is so important, because of course, it can inform our patients on active surveillance who have serial biopsies to ensure that we understand the possibility of missing things. But also for those patients who are undergoing their first biopsy, there obviously is a risk that we're not sampling the entire tumor. Obviously we're not, if we're just taking these certain spots. And MR guided biopsies are not as ubiquitous as we wish that they were. This is really impactful work as we just said. And wondering, I know that you've continued work on this project and you have some work that is culminating now. Can you tell me a little bit about some of the rest of the work that was done under this award?
Simpa Salami: The second aim of the award was to look at prostate cancer in lymph node metastasis and ask the question, why is it that some focus of cancer will metastasize to the lymph node and some do not? And what we have done is to construct what we call phylogenetic analysis to see how prostate cancer started from normal cells and then how the trajectory of the cancer progressed to the point of metastasis. Really asking the question, what are the factors that predisposes certain prostate cancer focused to metastasis?
Alicia Morgans: So important. And how might you envision that this ultimately could be used in clinical practice?
Simpa Salami: First of all, what we've found so far is the fact that there's really no common theme that predicts metastasis to lymph node. And there's so many factors that we identified. There were driver alterations that we found to be particularly important for lymph node metastasis. We also found that there are some histologic characteristics like cribriform pattern that were important between lesions that we classified as being the dominant clone, and also found to be present in the lymph node metastasis. But there's really no specific theme that we could identify that cuts across all patients. And the implication of this is that really the mechanisms of metastasis is patient specific, and it's also important to think about developing therapeutic strategies that are also potentially patient specific.
Alicia Morgans: Well, that is no small task. But really identifying this issue is certainly the first step in solving the problem. So very, very excited that you and your team are able to bring this forward and really clarify it from a basic biologic perspective, using these samples that you have. So any final words and thoughts, maybe, on where you and the team are going to go next in terms of your pursuit of really understanding how to predict which lesions are going to be most aggressive and problematic for people?
Simpa Salami: Currently, I think a good way to approach this potentially will be to assemble patients with favorable risk disease and track them over time. So now we have the technology to serially sample the same cancer focus over time. And the idea is that we may be able to identify biomarkers that could predict patients that will ultimately progress well in surveillance and then identify those patients for treatment.
Alicia Morgans: Wonderful. Well, I certainly look forward to hearing more about this over time, and I congratulate you and your team for the amazing work you've already done on this award. Certainly there is much more to come, but thank you for your time today.
Simpa Salami: Thank you.