The Effect of Metastasis-Directed Therapy (MDT) on Oligometastatic Castration-Sensitive Prostate Cancer Outcomes - Philip Sutera
January 3, 2023
Philip Sutera, MD, Johns Hopkins University, Baltimore, MD
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
Alicia Morgans: Hi, I'm so excited to be at ASCO 2022 where I'm speaking with Dr. Phillip Sutera from Johns Hopkins about his work in metastasis-directed therapy. Thank you so much for talking with me about the presentation that you and the team had at ASCO 2022.
Philip Sutera: Thank you very much for having me.
Alicia Morgans: Wonderful. You and the team put together some really elegant work, thinking about metastasis-directed therapy and trying to help us understand the prognosis of patients after treatment and how we understand and predict, I guess, who's going to do well and who's not going to necessarily do as well and may need further intervention. Can you tell us a little bit about why you did the study and what you did?
Philip Sutera: Absolutely. Oligometastatic hormone-sensitive prostate cancer has previously been shown to derive benefit from metastasis-directed therapy. These are typically patients with hormone-sensitive disease with anywhere from three to five or fewer metastases where they're consolidated to all areas of disease with either stereotactic radiation or something like surgery. There's randomized data that currently exists that shows that metastasis-directed therapy in the space can actually prolong progression-free survival as well as ADT for free survival when these patients are treated compared to observation, and so it represents an exciting space for us to intervene with this therapy and try to delay or prevent progression or further therapy. What we did is we looked at these patients in two separate cohorts. One, a discovery cohort that we had at Johns Hopkins that were initially enrolled on the ORIOLE clinical trial, that was one of those randomized trials I was just mentioning.
Then, we had a validation cohort from Baskin University in Turkey. We selected for patients that had three or fewer metastases on conventional or enhanced PSMA imaging who then received metastasis-directed therapy to their disease. All patients had to have a PSMA PET scan prior to treatment, and then we also followed them up with a three to six-month post-PSMA scan. The idea here was we were looking to see what the PSMA SUV response was following metastasis-directed therapy, which is currently unknown. We then wanted to correlate that response with clinical outcomes, most notably metastasis-free survival, which in the localized space has been shown to be a very good surrogate for overall survival.
What we showed is that patients that have at least one lesion that has an increase in SUV max at that three to six-month scan, which we did a discrete cutoff at 20%, had a significantly worse metastasis-free survival. Looking at two-year MFS, those that had all lesions that did not have an increase in SUV had a 65% MFS versus 30% for those that had at least one lesion with a rising SUV, indicating that we can potentially use this PET scan as an early response indicator for which patients may need intensification of treatment.
Alicia Morgans: That's so important, because as you said, the studies have suggested that if we, for example, radiate every identifiable lesion, we can do better in terms of progression-free survival, hopefully shifting the trajectory of the disease because that's really what we're trying to do. If we can't, we already know that's not going to really be as successful. This is another way for us to judge and to talk with our patients about whether we're actually doing something meaningful. Now, your endpoint, metastasis-free survival, is that defined by conventional imaging, CTs, and bone scans, or is that something that's also PSMA based? The reason I ask is because the MFS endpoint that we've used really to be sort of connected to overall survival, and that seems to be so closely associated, is based on conventional imaging. But, it is so tempting in today's era to continue to scan with PSMA PETs.
Philip Sutera: Exactly, we understand that. Our MFS that we reported in our abstract was in fact using conventional imaging for that exact reason is that the surrogacy is so strong with conventional imaging, and as a field, I don't think we really understand how to apply PSMA. We also looked at PSMA radiographic progression-free survival and the results hold and are very similar, but specifically how we defined MFS was a new lesion outside of a pelvic lymph node, which is what the ice cap definition used. I think an important note to this is that if one of the lesions that was already present at diagnosis of oligometastatic disease was growing, we did not include that as a progression of a metastasis-free survival event, that was really a local failure, and so really we're looking at distant disease outside of what was already known.
Alicia Morgans: That's so helpful. Thank you for running through that, and certainly is a strength of the study. Another strength I think is really trying to also have PSMA PET information so you can understand if that's going to be tightly correlated or whether it's going to be completely unrelated, which is potentially a risk in this setting, so really, really exciting and comforting to know that they're probably associated. What else do you want us to know about this work?
Philip Sutera: I think one of the very interesting pieces about this work is anytime we're looking at response biomarkers, it's always easy to find something, but then to actually validate it I think is an important component. I think one of the strengths of our study is that we have an entirely separate cohort of patients from halfway around the world that were treated in a similar way, but obviously there's distinct differences in biomarkers really holding up in both two separate cohorts. I think that it gives credence to the fact that this is something that we can be using to try to predict for patients that will have poor outcomes. Potentially, if this were to be employed, it gives us an early sense of which patients need intensification of treatment. I think some of the other future work is also in identifying patients prior to treatment, of course, not needing to put patients through a treatment and then evaluating for their response. There's several projects underway as well to try to evaluate can we predict these patients before they go to treatment? But, at this point, we don't really have that information.
Alicia Morgans: It is really comforting to know that you are getting that information though, because as you said, that's really what we want to do, try to prevent overtreatment for patients where we can and to maybe intensify treatment for patients if that needs to happen, maybe systemic therapy in combination with this BRT, and maybe that is the best approach for those patients who have that early increase in their SUV. Lots of work to do, but you and your team are doing your best in actually doing a phenomenal job and helping to answer some of the most important questions in this setting. I really appreciate your time and your expertise.
Philip Sutera: Thank you very much.