Challenges & Advances in Phenotypic Precision Medicine

By Vanessa Ira - December 21, 2022

Jacqueline T. Brown, MD is a medical oncologist specializing in the treatment of patients with genitourinary malignancies at Winship Cancer Institute of Emory University in Atlanta, GA and an Assistant Professor within the Emory University School of Medicine. She is actively involved in clinical investigation of novel therapeutics in patients with genitourinary cancers in all phases of drug development and has a special interest in improving the management and quality of life of older patients with these cancers.

Dr. Brown sat with us to talk about current challenges and advances in phenotypic precision medicine, as well as treatment strategies for advanced prostate cancer.

What are some challenges and advances in phenotypic precision medicine treatment strategies for advanced prostate cancer?

Dr. Brown:  Yeah. I think that one of the biggest issues in this space is, when we have new types of imaging, like PSMA PET scan, this has really changed the game. It has a higher sensitivity and specificity than the conventional imaging we’ve used for a long time. And so now, we’re seeing disease that we didn’t see before. So, benefits of that are, in localized disease, that’s going to impact the way you treat a patient, is going to influence treatment decisions. And in more advanced diseases, it can help you to think about, okay, is there a role for SBRT or some kind of local therapy in someone with oligometastatic disease? Or for someone with more advanced disease, can I use lutetium therapy for that patient who has PSMA positive disease on the appropriate companion diagnostic test?

And so, it’s a brave new world, and I think a lot of our literature and our understanding hasn’t caught up to these new technologies. For example, all of our clinical trial definitions of high-volume disease or low-volume disease, that’s based on conventional imaging. So, when we have a PET scan, a PSMA PET scan, or Axumin PET scan that shows us more advanced disease than we would see on conventional imaging, we don’t know what to do with that. Because, all of our prospective trials, which have informed how we manage low-volume disease, for example, were based on conventional imaging. So, I think it’s going to take some time to understand what findings on these very sensitive imaging modalities, what their implications are on long-term prognosis and how we should manage those patients. Now we see things and we need to know what to do with it, and we aren’t sure right now. So, I think that’s a challenge.

I think another challenge, and I think most clinicians right now are dealing with this, is that, although lutetium-177 therapy was approved in 2022, currently due to supply chain issues, due to reimbursement issues, it’s not yet widely available. We have a lot of patients with metastatic castration-resistant prostate cancer who need that next line of therapy and are waiting for that. And so, I think all of us who treat these patients with advanced disease are anxiously awaiting to have this therapy more available, particularly because our data supporting its approval from the TheraP trial, from the VISION trial, we know that this is an efficacious therapy. And I think, most importantly, it’s a very well tolerated therapy. Patients seem to actually have improved quality of life, both in the TheraP trial and the VISION trial, compared to the comparator arms. And so, I think there is such a demand for this therapy and hopefully its delivery system will catch up in the near future so that it’s actually available for our patients.

And then, there’s a lot of unknowns. How does the degree of PSMA positivity on a scan impact prognosis? And I think we have some evidence to say that, that does have an impact on prognosis, but more work is needed in that space. Understanding how PSMA positive diseases defined, because it was defined differently in the TheraP trial compared to the VISION trial. We’re trying to catch up with the technology, which has just advanced so quickly. And I think that’s an excellent thing, both for our patients and for us, as docs. But meeting that moment with the best evidence-based medicine we can is going to take a little bit of time. So, I would say those are the biggest challenges.

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