Dr. Jia on metastasis directed radiotherapy in prostate cancer

In this interview, Angela Jia, MD, PhD, gives an overview of the session, “Updates on Metastasis Directed Therapy,” which was presented at the 2024 American Urological Association Annual Meeting in San Antonio, Texas. Jia is a radiation oncologist at University Hospitals/Case Western Reserve University in Cleveland, Ohio.

Video Transcript:

Metastasis directed radiation therapy is the concept where you give ablative doses of radiation. And by ablative, I mean doses meant to eradicate cancer, not simply a palliative dose of radiation, which we give all the time in the metastatic setting. But specifically, MDRT, metastasis directed radiation therapy, is using ablative doses. In the session, we talked about when is this appropriate in the context of prostate cancer? And what it meant and what I think the field is evolving now to mean. I would say historically, we have this concept of oligometastatic disease, oligo meaning few. Few, what? Few sites of metastatic disease, trying to find this in-between stage of a cancer that is localized vs a cancer that has spread everywhere. Finding an in-between phase, kind of like the cat left the bag, but isn't wildly around the city. The cat's on a leash, kind of thing. In that oligo state is where most of the evidence for MDRT has been generated. With the thought of, let's select favorable patients–albeit metastatic, but still favorable. We may have perhaps a chance to still cure them from their disease. Let's use MDRT on those patients. That's what historically, I would say the trials have been on.

Because we limit the number of mets to 3 to 5 in the prostate world. We oftentimes would say, "oh, some of the trials have synchronous disease." By synchronous, I mean the patient was metastatic at the time that you discover there was any prostate cancer vs metachronous, meaning the primary prostate has already been treated, he wasn't metastatic to begin with, and now after some time, he appeared to have metastatic disease. So, I would say most the evidence have been in the metachronous setting with limited amount, this 3 to 5 number. This number was picked, almost like a practical number of well, how many sites do we think we can safely treat? But what we've seen is a favorable side effect profile using stereotactic ablative radiation therapy, with very good progression-free survival benefits.

So, seeing that this is a tool, we can almost think of it as a tool of giving effective cytoreduction of tumors, not dissimilar to chemotherapy, for example. Once we think of it more [as] that tool, I think we don't need to limit ourselves to the most favorable patients. Instead think of it as a tool of yes, maybe patients who are potentially curable, but maybe also patients who do have high-risk disease, maybe not so favorable. We can use this to cyto reduce, eliminate resistant clones, and ultimately improve the quality of life. I'm also aware, we're not trying to do mission creep, where we're trying to offer ablative radiotherapy to everyone out there. That would not be appropriate. I think it's a sit-down discussion of what are your goals of care. As with everything in medicine, it is what are your goals of care?

If the goals of care are to avoid ADT, which is a goal for some patients who have intolerable side effects from ADT. If that is your goal, then we can certainly use MDRT to buy us time. And we can repeat MDRT as needed. There's a metastases in this bone, we treat it and 3 months later, we scan and another metastasis pop up, we can treat that, all the while trying to keep this patient off of systemic therapy. That's one goal. If the goal is instead to maximize local control then I would say, yes, you should add on hormonal therapy. It helps. It radio sensitizes, so it certainly helps your radiation. If the goal is ultimately to just eliminate all resistant clones, then it should be the maximum amount of therapy, so that would be ADT plus an androgen receptor pathway inhibitor plus the MDRT–everything on board. I think ultimately, when we think about when do we deliver MDRT and to whom, it comes down to a goals of care discussion.

This transcription has been edited for clarity.