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Julian Hong: Well, I'm going to be talking about oligometastatic-directed therapy, specifically SBRT. No discussion of oligometastasis is complete without some reference to the University of Chicago and the work done by Sam Hellman and Ralph Weichselbaum. And of course, this is, I think, probably at this point now, a classic figure proposing this intermediate state and this transition between localized disease to widely metastatic cancer.

And of course, the tagline is that there are scenarios where oligometastasis may lend itself to potentially curative therapy, or at the very least, intervals of extended disease-free survival.

And so the University of Chicago had broadly set up studies investigating oligometastasis across a number of different cancers, and these extended to other institutions as folks from UChicago moved on. And across these studies, I had the opportunity to work on some of the data there. And you'll notice, this is back when recursive partitioning analysis was still cool before AI, but we found that there are a number of disease subtypes that lend themselves to better outcomes with metastasis-directed therapy, including prostate cancer, of course. And these scenarios were actually independent of other very traditional classic indicators of better outcomes.

So, of course, the timing of oligometastasis is important. This concept of both synchronous oligometastatic disease, but also metachronous oligorecurrence. And most of our data in the treatment of oligometastatic cancer exists in the latter stage. So this is just a smattering of a number of the major studies in oligometastatic prostate cancer with metastasis-directed therapy. I'll highlight that, as you can see in all of the titles, these are all Phase II randomized trials.

The current—I think to address the tagline of this talk—the current state of determining best candidates for therapy is still largely numerically defined, which, as many of us know and think, is fairly crude. But these are the number of metastases that define the eligibility across each of these different studies. And you can see there's a little bit of heterogeneity, traditionally 1 to 3, 1 to 5 depending on the study.

Most of these studies are also in the castration-sensitive setting. And so I'll just highlight that the more recent ARTO trial included specifically patients with castration-resistant disease, which is a nice study to provide broader application of metastasis-directed therapy.

The other key concept in the current stage, particularly relevant to this conference, is the phenomenon of stage migration. And so a number of the studies that I listed earlier were defined—or defined oligometastasis—based on conventional imaging. As we know, PSMA PET has enabled the greater detection and greater specificity of detection of metastatic prostate cancer.

And so these three studies at least included PSMA as some component, whether it's in defining the eligibility, or—I left an asterisk next to the ORIOLE trial—provided some extra analysis in understanding how PSMA interacts with treatments. And so these are all important things as we're considering candidacy for SBRT and metastasis-directed therapy. This phenomenon of stage migration does make it hard for that quantitative cutoff to be applied in a systematic fashion. I'd also say that this is an area of continuing evolution, as there are a number of studies—I highlight the SABR-COMET-10 trial—looking to see if we can expand upon the current numeric definitions.

So I thought I'd include some slides to ask, can we do better? Can we move beyond some of these crude metrics? And so the STOMP and ORIOLE groups have done a wonderful job in doing some secondary analyses of their data. This first one is a study applying the multimodal AI from Artera to the cohorts from STOMP and ORIOLE.

And what it shows us is that the MMAI high patients may potentially have a greater benefit from metastasis-directed therapy. So this model, which was developed in a different type of cohort, may have a secondary use in looking at oligometastasis candidacy.

The group has also looked at PSMA-positive extracellular vesicles, which may provide an additional biomarker. And so very similarly, it provides an ability to evaluate a group of patients where there may be a greater separation in the benefit of SBRT. And then this data is not published yet, but was presented at ASTRO and I believe at one of the ASCO conferences previously as well—some work that this group is doing on circulating tumor cells as well.

And then I'll round out, because we're at a PSMA Conference, so I thought I'd talk a little bit about PSMA and evaluating candidacy. So this is some work done by our team led by Will Chen, who's going to be starting on faculty this fall, looking at our experience with metastasis-directed therapy. And we've been applying computer vision or AI approaches toward trying to evaluate PSMA PET scans to try to identify characteristics that may portend for better or worse outcomes.

And on top of that, we've been trying to evaluate whether or not there's some intralesional—or interlesional—heterogeneity within a single patient to see if there's greater risk for certain lesions to portend future castrate resistance. And so that's some ongoing work where we're trying to define better groups for whom we can treat with SBRT.

And then I will leave us with the NCCN Guidelines for metastasis. As was mentioned in the last talk, not a whole lot of guidance in metastasis, but here in the NCCN Guidelines, very briefly, that limited metastatic disease where ablation is the goal or in oligoprogression, which lends some flexibility to clinical discretion. And I'll leave off with just saying that currently, we define candidacy based on disease burden, we should continue to generate high-quality data in trials, and then hopefully advance selection through biology. And I will wind things down. Thank you.