Non-Metastatic HSPC: Evaluating Imaging Strategies, Post-Salvage Treatment Options

A roundtable discussion, moderated by Pedro Barata, MD, of University Hospitals, highlighted the evolving treatment landscape of advanced prostate cancer, including hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). The panelists analyze expanding treatment intensity, the utilization of androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs), and integrating patient-reported outcomes (PROs) in care. Dr. Barata was joined by Andrew Armstrong, MD, MSc, of Duke University School of Medicine; Cora Sternberg, MD, of Weill Cornell Medicine; and Evan Yu, MD, of UW Medicine.

In the second segment of our roundtable series, the panelists discuss their approaches to the use of PSMA PET for patients and review post-salvage treatment options.

View the next segment of this roundtable series: Advancing Treatment Strategies in mHSPC: Addressing Disparities and Optimizing Care

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Dr. Barata:
So Cora, let me get back to you. Andrew mentioned something and I think Evan brought it up again – when we look at the population, we probably would expect a lot of those patients who have metastatic disease to have a better scan with PET scans.

I think maybe we were or have been a little bit behind some of the other areas of the world where PSMA PET has been used due to better cost. I think we’re getting there, and in this recurrence setting, I think most of us are currently using PSMA PET.

Some would argue that we’re moving this agent early and if I see metastatic disease, they are all sensitive. We would still use data, extrapolating data from ARCHES or ENZAMET.

Regardless of seeing metastatic disease, some would still consider enzalutamide in this setting even if the PET is positive.

All of this to ask you, for patients with PET positive, CT scan negative, conventional scan negative, is that your approach?

Dr. Sternberg:
In our hospital, it’s been fairly easy to get a PSMA PET, which is not true all over the world, not even in Germany where they use it a lot. So we do use PSMA PET, but if there’s absolutely nothing on conventional imaging, I think we have to take that into account as well.

I think that there can be mistakes if you just take the PSMA PET, and sometimes PSMA PET can show up other things, like other diseases or benign diseases.

I think it’s an important thing to know that if the PSMA PET is positive in many places, we often will do biopsies to see what we’re doing with it. With interventional radiology, again, I work in an academic center where I have all that available. But I think most people who work in the community don’t have the access to the PSMA PET.

The EMBARK study was not done with PSMA PET, it was done with conventional imaging. We have to remember that, too.

Dr. Armstrong:
I have to say, it is a more small-volume disease where the goal of many patients is to not have continuous therapy forever. So I think if you can get to a point where you can stop therapy and enjoy a year or two or three off therapy, some of the strategies to have that prolonged break are doublet therapy.

When you use enzalutamide monotherapy, your testosterone’s very high. So as soon as you release them from enzalutamide, there’s a very short time before that PSA goes right back up again. But if you’re on doublet therapy, there’s about 21 months of remission.

Other strategies are metastasis-directed therapy. Some people employ that to delay ADT, but you could also employ it – such as in the EXTEND study or the STAMPEDE2 study – to try to destroy those micro-metastatic sites. You can combine that with best systemic therapy, but then stop the best systemic therapy so you can get a very long off-period.

Dr. Sternberg:
I like the EXTEND study very much; we give patients with oligometastatic disease SPRT and then combination therapy for six months and then stop.

Dr. Yu:
I’m going to say something that might be controversial, but I don’t get PSMA PET on everyone in this disease state. Here’s what I do in advance: I have the discussion with the patient about what I would do with the PSMA PET – “if it shows this, I might consider that.”

If the patient says that they don’t like it or would never consider it, and I can already reach for systemic therapy with androgen deprivation therapy and enzalutamide in this setting, then what do I need to find a couple extra metastases for on PSMA PET?

Now if the patient says that they know there’s data to show that metastasis-directed therapy can kick the can down the road until I have to start androgen deprivation therapy, and if they’re familiar with these terrible things about the androgen deprivation therapy side effects and they’re interested in that, then that would be a good reason to get it.

But it’s a good old thing you learn in med school, don’t get a test unless you know if you’re going to do something with it. If you get a test and you know, you just see it there and then you put them on androgen deprivation therapy and enzalutamide. At this point in time, the patient may not need to get that PSMA PET.

Dr. Barata:
Wonderful discussion. So based on these data, are any of you still considering ADT alone?

Dr. Armstrong:
Absolutely. I mean, ADT alone has less toxicity. I think regardless of your decision, you need to maintain a survivorship-focused approach, you know, where you’re mitigating adverse events, focusing on cardiovascular bone health, and encouraging exercise.

These men are living a decade or more on or off ADT, with or without enzalutamide, and there’s a lot of comorbidity that goes with that. So home blood pressure monitoring, encouraging an exercise program, and monitoring bone health.

There are some men that are just not candidates for a doublet therapy because of those comorbidities, and ADT has been practiced for many, many years with decades of survival. So it is appropriate for some men.