There’s huge progress right now. There are so many ways to look at it. We can go to our very traditional biomarkers, which include everything such as pain, hemoglobin, prostate-specific antigen (PSA), alkaline phosphatase (AP), and lactate dehydrogenase (LDH). We can then move on to our image-based biomarkers, which are rapidly changing right now, with things like the prostate-specific membrane antigen (PSMA) scan, choline positron emission tomography (PET) scan, etc. And then we can go into the molecular biology. We can now not only count circulating tumor cells (CTCs), but we can also evaluate CTCs from a molecular perspective, and we can look at circulating free DNA (cf-DNA) as well. There are a huge number of improvements and alterations right now, I think particularly at the molecular level and regarding cf-DNA. That’s where I see a lot of things going on.

Yes, Oliver, I think that’s true. Although I would say right now, what’s available for clinicians are really 2 factors: the volume of disease at the time of hormone-sensitive prostate cancer metastasis (mHSPC) and the course of action or path taken to get there. Are these de novo cases, or are these previously treated localized cases that are now relapsed over time? Those 2 factors seem to be really prognostic – and well established as prognostic, in multiple series – and we saw a couple of those abstracts at the American Society of Clinical Oncology Genitourinary Symposium (ASCO-GU) this year. I think that’s going to be the clinical backdrop in which we evaluate some of these newer molecular markers and newer ways of understanding the biology that’s going with that. Then, to take it one step further, we’d consider the patients with oligometastatic disease. They would presumably be in the low-volume disease category; they would also potentially be among patients who are slower to develop metastases, meaning they have localized disease that developed into oligometastatic disease. That’s going to be the clinical context in which we evaluate all of these markers, rather than the “all-comers”-type population.

I think one of the issues really going on right now is whether or not we can get better imaging. There is currently a lot of momentum toward examining the failures of bone scan and computed tomography (CT) scan. The goal is to help find ways to diagnose high- vs low-risk disease, to get at the populations that we’re really trying to distinguish. For example, who should get chemotherapy in mHSPC? Also, for patients with rising PSAs who have no overt metastasis – these are patients who, let’s say, have failed surgery or radiation, and yet we still can’t accurately locate the site of their malignancy. It’s very frustrating for patients and clinicians. For example, I think we’re seeing a lot of momentum with Gallium and the F-18 PSMA tests. There’s a new test approved in the United States called F-18 fluciclovine that we’ve been using. It seems to be more sensitive and may be more specific at picking up small metastases. I think the questions with imaging will be:

• Will we have better tools?
• Do we have better tools now, to identify where the cancers are?
• Can we potentially stratify these patients to get the appropriate specific therapy, such as chemotherapy?