®: “Prostate Cancer Evolving Treatment Approaches.” I’m Dr Dan George from the Duke Cancer Institute in Durham, North Carolina. Joining me today in this discussion are my colleagues Dr Tanya Dorff from the City of Hope Comprehensive Cancer Center in Duarte, California; Dr Eleni Efstathiou from The University of Texas MD Anderson Cancer Center in Houston, Texas; Dr Ben Lowentritt from the Chesapeake Urology Group in Towson, Maryland; and Dr Chuck Ryan from the University of Minnesota Medical School in Minneapolis, Minnesota. At the midpoint of 2020, it’s been another exciting year in the field of genitourinary oncology. In the field of prostate cancer in particular, we have made significant progress with several recent FDA approvals.

Today, we’re going to discuss a number of the systemic therapies for advanced prostate cancer. We’ll highlight the latest research in the field and discuss practical implications for patient care. Let’s get started with our first talk. We’re going to start out with emerging data around metastatic castration-sensitive prostate cancer. We’re going to follow this up with a segment on nonmetastatic castration-resistant prostate cancer, and then finally end with a segment on metastatic castration-resistant prostate cancer. We’ll discuss both the therapies we have today and some of the emerging treatments and how they are going to impact our care.

Let’s start with metastatic castration-sensitive prostate cancer and exactly how we get there. Many of these patients are presenting with biochemically recurrent prostate cancer after being monitored. The question I have first is, what’s the optimal timing and frequency of imaging? Is that imaging modality changing now with some of the newer PET [positron emission tomography] scans? What are the data around that? Where do we see that emerging now in our regular practice? I’ll start with you, Chuck. Could you walk us through this next generation of imaging and the impact of the timing of diagnosis of metastatic prostate cancer? Can you talk to us a bit about some of the PSMA [prostate-specific membrane antigen]–targeted imaging and where the data are pointing us, in terms of that implication?

 Sure, Daniel. Thank you. It’s really important, before we have a conversation about how to treat castration-sensitive metastatic prostate cancer, to figure out what that clinical state is. As you alluded to, it’s becoming a wider range of clinical entities because our imaging is getting much more sensitive. This is 1 of the areas with the most rapid change in our field. As you said, PSMA-targeted imaging is leading the way. We had 3 presentations at ASCO [American Society of Clinical Oncology Annual Meeting] that helped us with this concept.

Two of the abstracts looked at a molecule called fluorine F 18 DCFPyL, which targets PSMA. Another looked at gallium Ga 68–labeled PSMA-11. They’re using different isotopes for imaging. More important, they looked at different clinical states. The OSPREY trial that was presented was with a pretherapy, newly diagnosed group of patients. Virtually all those patients had negative CT [computed tomography] and bone scans. When they went through the PSMA imaging, we found that 15% of the patients imaged with this new modality actually had N1 disease, and almost 11% of the patients actually had metastatic disease that was entirely missed by the standard imaging.

In that group of metastatic disease, 9% had M1b, or regional disease, and 1% or so had distant metastatic disease. That means that potentially 25% or even more of the patients who are currently diagnosed as having localized prostate cancer will actually have some element of metastatic disease, so that’s something we should discuss. The other study is the CONDOR study, which used the same imaging modality but looked at patients who had a rising PSA [prostate-specific antigen] level after local therapy. CONDOR demonstrated that these images do change the therapy.

That was the key end point of CONDOR. Do we change what we do with the patient based on novel imaging? About 69% of the patients who were imaged had positive scans, and in 64% of the patients who were imaged, treatment was affected by the scan. What was interesting about these changes in imaging is that they led to systemic therapy in about a third, focal therapy in about a third, and observation in about a third. There is a lot to discuss there.

Finally, as for gallium Ga 68–labeled PSMA-11, there is obviously a lot of work going on with regard to metastatic disease and how we’re going to see it integrated into oligometastatic detection, etc. This study, presented by Thomas Hope from University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center looked at preoperative, pretherapy patients. It suggested a very high sensitivity and specificity for gallium Ga 68-labeled PSMA-11 with PET, so that is also an imaging modality that’s going to drive how urologists and radiation oncologists are going to approach localized disease and who they’re going to include as having metastatic versus localized disease.

 There is a lot to digest there, because it really is a paradigm shift, especially when we think about it in a preoperative, prelocal therapy setting. How much of this is going to impact treatment? How clinically relevant is that? Or is this just another way of characterizing microscopic spread of disease?

Benjamin H. Lowentritt, MD, FACS, Chesapeake Urology

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PSMA-Targeted Imaging in Prostate Cancer